Sign in to use this feature.

Years

Between: -

Subjects

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Journals

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Article Types

Countries / Regions

remove_circle_outline
remove_circle_outline
remove_circle_outline
remove_circle_outline

Search Results (320)

Search Parameters:
Keywords = anxiety/depression-like behaviors

Order results
Result details
Results per page
Select all
Export citation of selected articles as:
18 pages, 3824 KiB  
Article
Changes in Artemin Correlate with Anxiety- and Depression-like Behaviors in a Lipopolysaccharide-Induced Rat Neuroinflammation Model
by Hasan Çalışkan and Seda Koçak
Biomolecules 2025, 15(8), 1192; https://doi.org/10.3390/biom15081192 - 19 Aug 2025
Abstract
Artemin is a neurotrophic factor that belongs to the four-member family of Glial-derived growth factors. This study aims to investigate changes in artemin correlated with anxiety and depression-like behaviors in a neuroinflammation rodent model. In adult male Wistar rats, neuroinflammation was established through [...] Read more.
Artemin is a neurotrophic factor that belongs to the four-member family of Glial-derived growth factors. This study aims to investigate changes in artemin correlated with anxiety and depression-like behaviors in a neuroinflammation rodent model. In adult male Wistar rats, neuroinflammation was established through administration of 2 mg/kg LPS. Anxiety-like behaviors and locomotor activity were evaluated by the open field test. The sucrose preference test and the splash test analyzed depression-like behaviors. Tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and artemin levels were measured in the prefrontal cortex, striatum, and serum. In the neuroinflammation group, rearing, total distance traveled, time spent in the central region, and sucrose solution consumption decreased in the open-field test (p < 0.0001). Grooming time and frequency were shortened, and grooming latency was prolonged in the neuroinflammation group (p < 0.0001). TNF-α was significantly increased in the prefrontal cortex (p < 0.05) and striatum (p < 0.01). lL-1β did not change between groups (p > 0.05). Artemin levels decreased in the prefrontal cortex and striatum (p < 0.05). No difference was observed in serum artemin levels; however, artemin levels of brain regions were higher than those in the serum. An increase in anxiety–depression-like behaviors has accompanied decreased levels of artemin in the brain. Artemin may be a target molecule in psychiatric disorders. Further studies are needed to examine the role of artemin in neuropsychiatric disorders. Full article
(This article belongs to the Special Issue Neuroimmune Interactions in Neuropsychiatric Diseases)
Show Figures

Figure 1

30 pages, 7206 KiB  
Article
Preventing Cisplatin-Induced Neuropathy and Related Emotional Disorders with the Coadministration of Duloxetine and Hydrogen-Rich Water in Male and Female Mice
by Ignacio Martínez-Martel, Sylmara Esther Negrini-Ferrari and Olga Pol
Antioxidants 2025, 14(8), 1004; https://doi.org/10.3390/antiox14081004 - 16 Aug 2025
Viewed by 160
Abstract
Cisplatin (CIS)-induced peripheral neuropathy and associated comorbidities have a detrimental effect on the lives of cancer patients. Currently, there are no effective therapies to alleviate these symptoms. Duloxetine (DULO) is a recommended treatment, but it is linked with important side effects, thus making [...] Read more.
Cisplatin (CIS)-induced peripheral neuropathy and associated comorbidities have a detrimental effect on the lives of cancer patients. Currently, there are no effective therapies to alleviate these symptoms. Duloxetine (DULO) is a recommended treatment, but it is linked with important side effects, thus making it essential to explore novel approaches. We examined the impact of a prophylactic treatment with a low dose of DULO combined with hydrogen-rich water (HRW) on CIS-injected C57BL/6 male and female mice as a possible therapy for allodynia, muscle and body weight deficits, and emotive syndromes accompanying this type of chemotherapy. The prophylactic treatment with DULO and HRW prevented mechanical allodynia caused by CIS in both sexes and had greater effects than either treatment given individually. The combined treatment also prevented cold allodynia in male mice but only reduced it in females. Moreover, the coadministration of DULO with HRW avoided muscular deficits in both sexes. Furthermore, the body weight reduction induced by CIS in both sexes was not entirely mitigated by the combined therapy. However, all treatments avoided the anxiety- and depressive-like behaviors elicited by CIS. The antiallodynic actions and prevention of muscular deficits produced by the combined treatment might be explained by the inhibition of oxidative stress, inflammatory responses, and plasticity alterations provoked by CIS in the dorsal root ganglia of these subjects. This study proposes, for the first time, the cotreatment of DULO with HRW as an effective therapy for CIS-induced peripheral neuropathy and reveals the influence of sex on these actions. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
Show Figures

Figure 1

15 pages, 320 KiB  
Article
The Relationship Between Gestational Diabetes, Emotional Eating, and Clinical Indicators
by Tuğçe Taşar Yıldırım, Çiğdem Akçabay, Sevler Yıldız and Gülşen Kutluer
Medicina 2025, 61(8), 1447; https://doi.org/10.3390/medicina61081447 - 12 Aug 2025
Viewed by 258
Abstract
Background and Objectives: Gestational diabetes mellitus (GDM), which is becoming increasingly common in contemporary society, is recognized for its considerable psychosocial impact on pregnant women throughout the perinatal phase. The purpose of this research was to explore the possible links between mental [...] Read more.
Background and Objectives: Gestational diabetes mellitus (GDM), which is becoming increasingly common in contemporary society, is recognized for its considerable psychosocial impact on pregnant women throughout the perinatal phase. The purpose of this research was to explore the possible links between mental health status and dietary habits among pregnant women diagnosed with GDM, alongside examining how these factors correlate with clinical indicators like HbA1c measurements and the necessity for insulin therapy. Materials and Methods: The study included 82 pregnant participants, 37 with gestational diabetes mellitus and 45 without. Blood samples were collected from all participants for biochemical analysis, including fasting blood glucose, postprandial blood glucose, and HbA1c levels, which can be clinical indicators for the presence of gestational diabetes mellitus, and the need for insulin treatment was recorded. Then, participants completed a questionnaire collecting sociodemographic and clinical data as well as the Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI), Salzburg Emotional Eating Scale (SEES), and REZZY Eating Disorders Scale (REZZY). Data were statistically analyzed. Results: A previous diagnosis of gestational diabetes was more frequent in the case group (18.9%) than in the control group (2.2%) (p = 0.020). OGTT positivity was detected in 56.8% of the case group, whereas all control participants had negative results (p < 0.001). There were no statistically significant differences between the two groups in psychological symptom scores or eating behavior assessments (p > 0.05). Conclusions: Pregnant women with gestational diabetes mellitus were observed to score higher on measures of anxiety, depression, and emotional eating, particularly in response to negative emotions. These findings may indicate a potential association between gestational diabetes and psychological or behavioral factors related to metabolic regulation during pregnancy. Full article
(This article belongs to the Section Obstetrics and Gynecology)
23 pages, 5387 KiB  
Article
Tabernanthalog, a Non-Hallucinogenic Psychedelic, Alleviates Cancer-Induced Cognitive Deficits via Serotonergic Pathways
by Masahide Arinaga, Jun Yamada, Shoichiro Maeda, Ayumi Okamura, Yuto Oshima, Liye Zhang, Yiying Han, Kyoko M. Iinuma and Shozo Jinno
Int. J. Mol. Sci. 2025, 26(15), 7519; https://doi.org/10.3390/ijms26157519 - 4 Aug 2025
Viewed by 471
Abstract
Cancer-related cognitive impairment (CRCI)—encompassing anxiety, depression, and memory deficits—significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a [...] Read more.
Cancer-related cognitive impairment (CRCI)—encompassing anxiety, depression, and memory deficits—significantly diminishes the quality of life in patients with cancer, yet remains underrecognized in clinical practice. In this study, we investigated the therapeutic potential of tabernanthalog (TBG), a non-hallucinogenic analog of psychedelic compounds, as a novel intervention for CRCI using a Lewis lung carcinoma (3LL) mouse model. Behavioral assessments revealed heightened anxiety-like behavior and memory impairment following 3LL cell transplantation. Biochemical analysis revealed reduced tryptophan levels in both blood and hippocampal tissue, accompanied by the downregulation of serotonergic receptor genes and upregulation of pro-inflammatory cytokine genes in the hippocampus of tumor-bearing mice. Additionally, microglial density and morphological activation were markedly elevated. TBG treatment reversed these behavioral deficits, improving both anxiety-related behavior and memory performance. These effects were associated with the normalization of microglial density and morphology, as well as the restoration of serotonergic receptor and cytokine gene expression. In vitro, TBG partially suppressed neuroinflammatory gene expression in BV-2 microglial cells exposed to conditioned medium from 3LL cells. Collectively, these findings suggest that TBG alleviates CRCI-like symptoms by modulating neuroinflammation and microglial activation. This study highlights TBG as a promising therapeutic candidate for improving cognitive and emotional functioning in patients with cancer. Full article
(This article belongs to the Special Issue Physiological Functions and Pathological Effects of Microglia)
Show Figures

Graphical abstract

24 pages, 2128 KiB  
Article
Central Insulin-Like Growth Factor-1-Induced Anxiolytic and Antidepressant Effects in a Rat Model of Sporadic Alzheimer’s Disease Are Associated with the Peripheral Suppression of Inflammation
by Joanna Dunacka, Beata Grembecka and Danuta Wrona
Cells 2025, 14(15), 1189; https://doi.org/10.3390/cells14151189 - 1 Aug 2025
Viewed by 571
Abstract
(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with [...] Read more.
(1) Insulin-like growth factor-1 (IGF-1) is a neurotrophin with anti-inflammatory properties. Neuroinflammation and stress activate peripheral immune mechanisms, which may contribute to the development of depression and anxiety in sporadic Alzheimer’s disease (sAD). This study aims to evaluate whether intracerebroventricular (ICV) premedication with IGF-1 in a rat model of streptozotocin (STZ)-induced neuroinflammation can prevent the emergence of anhedonia and anxiety-like behavior by impacting the peripheral inflammatory responses. (2) Male Wistar rats were subjected to double ICVSTZ (total dose: 3 mg/kg) and ICVIGF-1 injections (total dose: 2 µg). We analyzed the level of anhedonia (sucrose preference), anxiety (elevated plus maze), peripheral inflammation (hematological and cytometric measurement of leukocyte populations, interleukin (IL)-6), and corticosterone concentration at 7 (very early stage, VES), 45 (early stage, ES), and 90 days after STZ injections (late stage, LS). (3) We found that ICVIGF-1 administration reduces behavioral symptoms: anhedonia (ES and LS) and anxiety (VES, ES), and peripheral inflammation: number of leukocytes, lymphocytes, T lymphocytes, monocytes, granulocytes, IL-6, and corticosterone concentration (LS) in the rat model of sAD. (4) The obtained results demonstrate beneficial effects of central IGF-1 administration on neuropsychiatric symptoms and peripheral immune system activation during disease progression in the rat model of sAD. Full article
(This article belongs to the Section Cells of the Nervous System)
Show Figures

Figure 1

14 pages, 257 KiB  
Article
Mental and Physical Health of Chinese College Students After Shanghai Lockdown: An Exploratory Study
by Jingyu Sun, Rongji Zhao and Antonio Cicchella
Healthcare 2025, 13(15), 1864; https://doi.org/10.3390/healthcare13151864 - 30 Jul 2025
Viewed by 417
Abstract
The mental and physical health of college students, especially in urban environments like Shanghai, is crucial given the high academic and urban stressors, which were intensified by the COVID-19 lockdown. Prior research has shown gender differences in health impacts during public health crises, [...] Read more.
The mental and physical health of college students, especially in urban environments like Shanghai, is crucial given the high academic and urban stressors, which were intensified by the COVID-19 lockdown. Prior research has shown gender differences in health impacts during public health crises, with females often more vulnerable to mental health issues. Objective: This study aimed to comprehensively assess the physical and psychological health of Chinese college students post-lockdown, focusing on the relationship between stress, anxiety, depression, sleep patterns, and physical health, with a particular emphasis on gender differences. Methods: We conducted a cross-sectional study involving 116 students in Shanghai, utilizing psychological scales (HAMA, IPAQ, PSQI, SDS, FS 14, PSS, SF-36) and physical fitness tests (resting heart rate, blood pressure, hand grip, forced vital capacity, standing long jump, sit-and-reach, one-minute sit-up test and the one-minute squat test, single-leg stand test with eyes closed), to analyze health and behavior during the pandemic lockdown. All students have undergone the same life habits during the pandemic. Results: The HAMA scores indicated no significant levels of physical or mental anxiety. The PSS results (42.45 ± 8.93) reflected a high overall stress level. Furthermore, the PSQI scores (5.4 ± 2.91) suggested that the participants experienced mild insomnia. The IPAQ scores indicated higher levels of job-related activity (1261.49 ± 2144.58), transportation activity (1253.65 ± 987.57), walking intensity (1580.78 ± 1412.20), and moderate-intensity activity (1353.03 ± 1675.27) among college students following the lockdown. Hand grip strength (right) (p = 0.001), sit-and-reach test (p = 0.001), standing long jump (p = 0.001), and HAMA total score (p = 0.033) showed significant differences between males and females. Three principal components were identified in males: HAMA, FS14, and PSQI, explaining a total variance of 70.473%. Similarly, three principal components were extracted in females: HAMA, PSQI, and FS14, explaining a total variance of 69.100%. Conclusions: Our study underscores the complex interplay between physical activity (PA), mental health, and quality of life, emphasizing the need for gender-specific interventions. The persistent high stress, poor sleep quality, and reduced PA levels call for a reorganized teaching schedule to enhance student well-being without increasing academic pressure. Full article
12 pages, 307 KiB  
Review
Motherhood and Childhood in the Context of Mental Illness: A Narrative Review
by Rosa Ayesa-Arriola, Claudia Parás and Alexandre Díaz-Pons
Women 2025, 5(3), 26; https://doi.org/10.3390/women5030026 - 23 Jul 2025
Viewed by 410
Abstract
Maternal mental illness significantly impacts caregiving, influencing both mothers and their children. This narrative review examines the challenges faced by mothers with conditions such as depression, anxiety, bipolar disorder, and schizophrenia, which often disrupt caregiving routines, emotional stability, and social integration. These difficulties [...] Read more.
Maternal mental illness significantly impacts caregiving, influencing both mothers and their children. This narrative review examines the challenges faced by mothers with conditions such as depression, anxiety, bipolar disorder, and schizophrenia, which often disrupt caregiving routines, emotional stability, and social integration. These difficulties can hinder secure attachments and contribute to adverse developmental outcomes in children, including heightened risks of anxiety, depression, behavioral issues, and cognitive impairments. Children of mothers with mental illnesses are 1.8 times more likely to develop emotional or behavioral problems and face a 2.7 times higher risk of suicidal ideation during adolescence. Intergenerational transmission of mental illness is also prevalent, with affected children showing a 2.5 times greater likelihood of developing mental illnesses in adulthood. Effective interventions include cognitive behavioral therapy (CBT), family-based approaches, and community programs integrating parenting education and mental health resources. These strategies have demonstrated improvements in maternal well-being and child resilience. The review highlights the need for comprehensive policies addressing maternal mental health, early intervention for children, and culturally sensitive support systems to break cycles of intergenerational mental illness. Future research should prioritize evaluating long-term intervention effectiveness and exploring innovative tools like digital mental illnesses solutions to support affected families. Full article
Show Figures

Figure 1

22 pages, 5061 KiB  
Article
Urolithin A Exhibits Antidepressant-like Effects by Modulating the AMPK/CREB/BDNF Pathway
by Yaqian Di, Rui Xue, Xia Li, Zijia Jin, Hanying Li, Lanrui Wu, Youzhi Zhang and Lei An
Nutrients 2025, 17(14), 2294; https://doi.org/10.3390/nu17142294 - 11 Jul 2025
Viewed by 682
Abstract
Background/Objectives: Urolithin A (UA), a gut-derived metabolite of ellagitannins or ellagic acid, has recently gained attention for its potential benefits to brain health. The present research aimed to assess the antidepressant-like properties of UA in both in vitro and in vivo models and [...] Read more.
Background/Objectives: Urolithin A (UA), a gut-derived metabolite of ellagitannins or ellagic acid, has recently gained attention for its potential benefits to brain health. The present research aimed to assess the antidepressant-like properties of UA in both in vitro and in vivo models and explored the molecular mechanisms underlying these effects. Methods: We investigated the antidepressant effects and mechanisms of UA in a model of corticosterone-induced damage to PC12 cells and in a model of chronic socially frustrating stress. Results: Our results demonstrate that UA treatment (5 and 10 μM) significantly alleviated cellular damage and inflammation in corticosterone (CORT)-treated PC12 cells. Furthermore, UA administration (50 and 100 mg/kg) significantly reduced immobility time in the mouse tail suspension test (TST) and forced swim test (FST), indicating its antidepressant-like activity. Additionally, treatment with UA led to the activation of the cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling cascade and triggered the activation of adenosine monophosphate-activated protein kinase (AMPK) during these processes. Importantly, pretreatment with AMPK-specific inhibitor Compound C abolished UA’s cytoprotective effects in PC12 cells, as well as its behavioral efficacy in the FST and TST, and its neurotrophic effects, highlighting the critical role of AMPK activation in mediating these effects. Furthermore, in the chronic social defeat stress (CSDS) mouse model, UA treatment (50 and 100 mg/kg) significantly alleviated depression-like behaviors, including reduced sucrose preference in the sucrose preference test, increased social avoidance behavior in the social interaction test, and anxiety-like behaviors, including diminished exploration, in the elevated plus maze test, suggesting the antidepressant-like and anxiolytic-like activities of UA. Moreover, UA treatment reversed elevated serum stress hormone levels, hippocampal inflammation, and the decreased AMPK/CREB/BDNF signaling pathway in the hippocampus of CSDS mice. Conclusions: Together, these results provide compelling evidence for UA as a viable dietary supplement or therapeutic option for managing depression. Full article
Show Figures

Figure 1

38 pages, 4834 KiB  
Article
Neuro-Inflammatory and Behavioral Changes Are Selectively Reversed by Sceletium tortuosum (Zembrin®) and Mesembrine in Male Rats Subjected to Unpredictable Chronic Mild Stress
by Johané Gericke, Stephan F. Steyn, Francois P. Viljoen and Brian H. Harvey
Cells 2025, 14(13), 1029; https://doi.org/10.3390/cells14131029 - 4 Jul 2025
Viewed by 1255
Abstract
Sceletium tortuosum (ST) induces antidepressant and anxiolytic effects, purportedly by monoamine regulation, anti-inflammatory and antioxidant properties, and phosphodiesterase 4 (PDE4) inhibition. These multimodal actions have not been demonstrated in an animal model of major depressive disorder. Wistar rats (both sexes) were subjected to [...] Read more.
Sceletium tortuosum (ST) induces antidepressant and anxiolytic effects, purportedly by monoamine regulation, anti-inflammatory and antioxidant properties, and phosphodiesterase 4 (PDE4) inhibition. These multimodal actions have not been demonstrated in an animal model of major depressive disorder. Wistar rats (both sexes) were subjected to 8-week unpredictable chronic mild stress, subsequently receiving saline, a standardized ST extract, Zembrin® 25 and 12.5 mg/kg (ZEM25 and ZEM12.5), its primary alkaloid mesembrine (MES), or escitalopram (20 mg/kg) for 36 days. Sucrose preference, open field, Barnes maze, and forced swim tests were performed, with cortico-hippocampal monoamines, inflammatory and oxidative stress markers analyzed post-mortem. Male, but not female rats, presented with increased anhedonia and anxiety but not despair. Males presented with increased hippocampal PDE4B expression, increased dopamine metabolites, and decreased cortical serotonin. In males, ZEM12.5 decreased anhedonia- and anxiety-like behavior, decreased cortical and hippocampal PDE4B, and increased plasma interleukin-10. MES induced a transient decrease in anhedonia-like behavior and increased hippocampal serotonergic and cortical dopaminergic activity, whilst decreasing hippocampal PDE4B. ZEM25 increased plasma interleukin-10 but decreased cortical glutathione, indicating paradoxical anti-inflammatory and prooxidant effects. ZEM12.5 and MES more effectively addressed anxious–depressive-like behavior and stress-induced inflammation and monoaminergic alterations, respectively. Multitargeted actions on monoamines, redox-inflammation, and PDE4 may provide ST with antidepressant effects across multiple symptom domains, although mutually synergistic/antagonistic effects of constituent alkaloids should be considered. Full article
(This article belongs to the Special Issue Neuroinflammation in Brain Health and Diseases)
Show Figures

Graphical abstract

22 pages, 2274 KiB  
Article
Quercetin and Tranylcypromine Improve Memory, Behavioral Performance, and Cholinergic Function in Male Rats Subjected to Chronic Restraint Stress
by Vitor Bastianello Mostardeiro, Charles Elias Assmann, Adriel Antonio Schirmann, Marcylene Vieira da Silveira, Bianca Vedoin Copês Rambo, Mairin Schott, Aline da Silva Pereira, Vanessa Valéria Miron, Heloiza Winck Soares, Larissa Varotto Dambrós, Sabrina Fontana Belinazo, Thamires Gelatti Vidal, Margarete Dulce Bagatini, Maria Rosa Chitolina Schetinger and Vera Maria Melchiors Morsch
Brain Sci. 2025, 15(7), 709; https://doi.org/10.3390/brainsci15070709 - 1 Jul 2025
Viewed by 597
Abstract
Background/Objectives: Major depressive disorder (MDD) is a debilitating illness, and chronic stress is a contributing factor for depressive symptoms. However, despite intense research, the mechanisms of MDD remain substantially unidentified. Quercetin is a powerful flavonoid and could be used as a possible [...] Read more.
Background/Objectives: Major depressive disorder (MDD) is a debilitating illness, and chronic stress is a contributing factor for depressive symptoms. However, despite intense research, the mechanisms of MDD remain substantially unidentified. Quercetin is a powerful flavonoid and could be used as a possible therapeutic strategy for depression. Acknowledging the potential benefits of quercetin, this study investigated its effect alone or in association with the standard drug tranylcypromine (TCP) in a rodent model of chronic restraint stress (CRS). Methods: Adult male rats were subjected to a CRS model consisting of an immobilization session of 4 h daily during 14 consecutive days. Quercetin (50 mg/kg, gavage) was administered for 45 days. TCP (10 mg/kg, gavage) was administered for 14 days. Behavioral tasks were conducted to assess locomotor functions, memory, anhedonia, depression-like behaviors, and anxiety-like behaviors. The activity, gene expression, and protein density of acetylcholinesterase (AChE) were investigated. Results: Behavioral tasks showed that the CRS model effectively induced stable behavioral changes. CRS did not alter locomotor function assessed by the open field test (OFT) or anhedonia behavior assessed by the sucrose preference test (SPT). CRS increased total fecal count, which was prevented by quercetin administration in rats. TCP and the association of quercetin and TCP increased the recognition index in comparison with the CRS group in the novel object recognition (NOR) test and improved the swimming and immobility times in comparison to stressed animals in the forced swim test (FST). All treatments were able to decrease the anxiety index assessed by the elevated plus maze (EPM) test. The activity, gene expression, and protein density of AChE were increased in the CRS model compared to control males. Overall, quercetin and TCP proved to reverse CRS-induced alterations in these parameters. Conclusions: Quercetin mitigated cognitive deficits, behavioral impairments, and neurochemical alterations induced by the CRS model, especially in association with TCP, supporting its potential as a promising therapeutic agent for depression. Full article
(This article belongs to the Special Issue Mental Health: From a Neurobiology Perspective)
Show Figures

Figure 1

23 pages, 17920 KiB  
Article
Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress
by Jiajun Yang, Yifei Jia, Ting Guo, Siqi Zhang, Jin Huang, Huiling Lu, Leyi Li, Jiahao Xu, Gefei Liu and Ke Xiao
Int. J. Mol. Sci. 2025, 26(13), 6063; https://doi.org/10.3390/ijms26136063 - 24 Jun 2025
Viewed by 662
Abstract
Organisms respond to environmental stress primarily through the autonomic nervous system and hypothalamic–pituitary–adrenal (HPA) axis, regulating metabolism, psychological states, and immune function and modulating memory, reward processing, and immune responses. The HPA axis plays a central role in stress response, exhibiting distinct activation [...] Read more.
Organisms respond to environmental stress primarily through the autonomic nervous system and hypothalamic–pituitary–adrenal (HPA) axis, regulating metabolism, psychological states, and immune function and modulating memory, reward processing, and immune responses. The HPA axis plays a central role in stress response, exhibiting distinct activation patterns under acute versus chronic social defeat stress. However, differences in physiological impacts and regulatory pathways between these stress conditions remain understudied. This study integrates RNA sequencing and behavioral analyses to reveal that acute social defeat stress triggers transient anxiety-like behaviors, accompanied by systemic inflammation and immediate-early gene (IEG) activation. In contrast, chronic social defeat stress induces long-term behavioral and physiological alterations, including neurotransmitter imbalance (e.g., reduced GABA and increased glutamate), sustained activation of maladaptive pathways (e.g., IL-17 signaling), and disrupted corticosterone synthesis. These findings highlight the dynamic regulatory role of the HPA axis under varying stress conditions, providing novel insights into mental health disorders such as anxiety and depression. The study identifies potential therapeutic targets to mitigate chronic social defeat stress effects and offers a theoretical foundation for personalized interventions. Full article
(This article belongs to the Section Molecular Neurobiology)
Show Figures

Figure 1

19 pages, 269 KiB  
Article
Understanding High-Risk Behavior in Mexican University Youth: Links Between Sexual Attitudes, Substance Use, and Mental Health
by Gustavo A. Hernández-Fuentes, Osiris G. Delgado-Enciso, Jessica C. Romero-Michel, Verónica M. Guzmán-Sandoval, Mario Del Toro-Equihua, José Guzmán-Esquivel, Gabriel Ceja-Espíritu, Mario Ramírez-Flores, Margarita L. Martinez-Fierro, Idalia Garza-Veloz, Fabian Rojas-Larios, Karla B. Carrazco-Peña, Rosa Tapia-Vargas, Ana C. Espíritu-Mojarro and Iván Delgado-Enciso
Healthcare 2025, 13(12), 1473; https://doi.org/10.3390/healthcare13121473 - 19 Jun 2025
Viewed by 753
Abstract
Background/Objectives: Sexual attitudes, particularly those on the erotophilia (positive openness) to erotophobia (negative fear) scales, play a critical role in shaping behaviors and health decisions. While associations between sexual behavior and substance use have been documented, limited research has explored how sexual attitudes [...] Read more.
Background/Objectives: Sexual attitudes, particularly those on the erotophilia (positive openness) to erotophobia (negative fear) scales, play a critical role in shaping behaviors and health decisions. While associations between sexual behavior and substance use have been documented, limited research has explored how sexual attitudes relate to mental health and substance use among Latin American university populations. This study aimed to examine the associations among erotophilic attitudes, mental health symptoms (anxiety and depression), substance use risk, and sexual behaviors in Mexican university students. Methods: A cross-sectional observational study was conducted between 2019 and 2023 with 1475 undergraduate students aged 17–25 years. Participants completed the Revised Sexual Opinion Survey (R-SOS) to assess sexual attitudes, the Hospital Anxiety and Depression Scale (HADS) for mental health evaluation, and adapted items from the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) to measure substance use risk. Erotophilic attitudes were defined as R-SOS scores ≥ 70. Statistical tests included the Kolmogorov–Smirnov test for normality, t-tests or Mann–Whitney U tests for group comparisons, Fisher’s exact test for categorical variables, and Spearman’s correlations. Multivariate binary logistic regression was used to calculate adjusted odds ratios (AdORs) and 95% confidence intervals (CIs), with a significance level of p < 0.05. Results: Erotophilic students were more likely to be male, older, initiate sexual activity earlier, and report a greater number of sexual partners. Erotophilia was positively associated with anxiety and tobacco, alcohol and marijuana use, and negatively associated with depressive symptoms. Multivariate analysis indicated that erotophilia was independently associated with male sex, age ≥ 20, higher anxiety, lower depression, low socioeconomic status, and increased risk of tobacco and marijuana use. Lower rates of consistent condom use were also reported among erotophilic individuals. Conclusions: Erotophilia may serve as a behavioral risk marker linked to anxiety symptoms and increased substance use, but not to depression. These findings highlight the need for integrated interventions addressing sexual health, substance use, and mental well-being in university populations. Full article
17 pages, 1134 KiB  
Article
Psychological Care Needs and Mental Health Service Use Among Adults with Diabetes: Evidence from the Diabetes, Distress, and Disparities (3D) Study
by Briana Mezuk, Kara M. Mannor, Rebecca Hebert, Lauren Kouassi, Bella Flores, Emma Spring and Alejandro Rodríguez-Putnam
Healthcare 2025, 13(12), 1427; https://doi.org/10.3390/healthcare13121427 - 14 Jun 2025
Viewed by 725
Abstract
Background/Objectives: Mental disorders and diabetes-related distress (DRD) are under-addressed aspects of person-centered diabetes care. This study examines the burden of depression, anxiety, and DRD among adults with type 1 (T1D), latent autoimmune diabetes in adults (LADA), type 2 (T2D), and gestational diabetes (GD), [...] Read more.
Background/Objectives: Mental disorders and diabetes-related distress (DRD) are under-addressed aspects of person-centered diabetes care. This study examines the burden of depression, anxiety, and DRD among adults with type 1 (T1D), latent autoimmune diabetes in adults (LADA), type 2 (T2D), and gestational diabetes (GD), and explores their experiences and barriers in receiving mental health services. Methods: This study uses quantitative data from the 2023/24 Diabetes, Distress, and Disparities (3D) Study, which is based at a large US medical center. The 3D Study consists of 573 adults with diabetes (51.3% with T1D or LADA, 43.5% with T2D, and 4.4% with current/past GD). Mental health assessments included the Patient Health Questionnaire-9 (depression), Generalized Anxiety Disorder-7 (anxiety), and Problem Areas in Diabetes-11 (DRD). Logistic regression was used to examine the prevalence of mental health concerns and behavioral service use. Results: Overall, 14.5% had clinically significant depression, 8.0% had anxiety, and 23.6% had elevated DRD. Symptoms of depression, anxiety, and DRD had a positive, non-linear relationship with poor glycemic control. Approximately 30% of those with clinically significant emotional health concerns did not receive any behavioral health services in the past 12 months. Black adults were less likely to receive behavioral health treatment than non-Hispanic Whites (Odds Ratio = 0.24, 95% CI: 0.07–0.77). Common reasons for not receiving behavioral health services included not knowing where to go, cost, and lack of accessible providers. Conclusions: Gaps in addressing the emotional health needs of people with diabetes persist. Healthcare systems need to integrate addressing psychosocial factors as part of person-centered diabetes care. Full article
Show Figures

Figure 1

28 pages, 13615 KiB  
Article
The Anti-Parkinsonian A2A Receptor Antagonist Istradefylline (KW-6002) Attenuates Behavioral Abnormalities, Neuroinflammation, and Neurodegeneration in Cerebral Ischemia: An Adenosinergic Signaling Link Between Stroke and Parkinson’s Disease
by Michael G. Zaki, Elisabet Jakova, Mahboubeh Pordeli, Elina Setork, Changiz Taghibiglou and Francisco S. Cayabyab
Int. J. Mol. Sci. 2025, 26(12), 5680; https://doi.org/10.3390/ijms26125680 - 13 Jun 2025
Viewed by 1598
Abstract
Stroke, the third leading cause of death worldwide, is a major cause of functional disability. Cerebral ischemia causes a rapid elevation of adenosine, the main neuromodulator in the brain. The inhibition of adenosine A2A receptors (A2ARs) has been introduced as a potential target [...] Read more.
Stroke, the third leading cause of death worldwide, is a major cause of functional disability. Cerebral ischemia causes a rapid elevation of adenosine, the main neuromodulator in the brain. The inhibition of adenosine A2A receptors (A2ARs) has been introduced as a potential target in neurodegenerative disorders involving extracellular adenosine elevation. Istradefylline, a selective A2AR antagonist, has been approved for Parkinson’s disease (PD) adjunctive therapy and showed neuroprotective effects in PD and Alzheimer’s disease. However, the role of A2ARs in post-stroke neuronal damage and behavioral deficits remains unclear. We recently showed that A2AR antagonism prevented the adenosine-induced post-hypoxia synaptic potentiation of glutamatergic neurotransmission following the hypoxia/reperfusion of hippocampal slices. Here, we investigated the potential neuroprotective effects of istradefylline in male Sprague-Dawley rats subjected to pial vessel disruption (PVD) used to model a small-vessel stroke. Rats were treated with either a vehicle control or istradefylline (3 mg/kg i.p.) following PVD surgery for three days. Istradefylline administration prevented anxiety and depressive-like behaviors caused by PVD stroke. In addition, istradefylline significantly attenuated ischemia-induced cognitive impairment and motor deficits. Moreover, istradefylline markedly reduced hippocampal neurodegeneration, as well as GFAP/Iba-1, TNF-α, nNOS, and iNOS levels after PVD, but prevented the downregulation of anti-inflammatory markers TGF-β1 and IL-4. Together, these results suggest a molecular link between stroke and PD and that the anti-PD drug istradefylline displays translational potential for drug repurposing as a neuroprotective agent for cerebral ischemic damage. Full article
Show Figures

Figure 1

18 pages, 5566 KiB  
Article
Multi-Strain Probiotics Alleviate Food Allergy-Induced Neurobehavioral Abnormalities by Regulating Gut Microbiota and Metabolites
by Shouxun Hu, Luanluan Li, Chunyan Zhou, Yue Zhang and Xiaodan Yu
Nutrients 2025, 17(12), 1955; https://doi.org/10.3390/nu17121955 - 8 Jun 2025
Viewed by 1125
Abstract
Background and aim: Neurobehavioral changes associated with food allergies have been reported, but the therapeutic effects of probiotics have not been fully explored. Our study aimed to investigate the impact of multi-strain probiotics on neurobehavioral outcomes and to elucidate the underlying mechanism via [...] Read more.
Background and aim: Neurobehavioral changes associated with food allergies have been reported, but the therapeutic effects of probiotics have not been fully explored. Our study aimed to investigate the impact of multi-strain probiotics on neurobehavioral outcomes and to elucidate the underlying mechanism via the microbiota-gut-brain axis. Methods: C57BL/6J Male mice were randomly divided into the following three groups: (1) control group; (2) OVA-sensitized group; (3) OVA-sensitized group treated with multi-strain probiotics (OVA + P). Anaphylactic reactions and behavioral abnormalities were assessed by histological, immunological, and behavioral analyses. To further elucidate the underlying mechanisms, the prefrontal cortex was collected for microglial morphological analysis, while serum and fecal samples were obtained for untargeted metabolomic profiling and 16S rDNA-based gut microbiota analysis, respectively. Results: Multi-strain probiotics significantly alleviated anaphylactic reactions in OVA-sensitized mice, as evidenced by reduced serum IgE levels, decreased Th2 cytokines, and reduced epithelial damage. Meanwhile, neurobehavioral symptoms were alleviated, including anxiety-like and depression-like behaviors, repetitive behaviors, social avoidance, and impaired attention. Mechanistically, probiotics administration suppressed production of inflammatory cytokines (TNF-α, IL-1β and IL-6) and inhibited activation of M1 microglia in the prefrontal cortex, which might contribute to neuron recovery. Furthermore, multi-omics analysis revealed that amino acid metabolism restoration in OVA + P mice, particularly carboxylic acids and derivatives, which was remarkably correlated with alterations in gut microbiota and behaviors related to FA. Conclusions: Gut microbiota and its amino acid metabolites mediate the therapeutic effects of multi-strain probiotics on FA-induced behavioral abnormalities. These effects occur alongside the suppression of neuroinflammation and microglial activation in the prefrontal cortex. Our findings highlight the neuroimmune regulatory role of the gut-microbiota-brain axis and support the potential use of probiotics as an intervention for FA-induced brain dysfunctions. Full article
(This article belongs to the Section Prebiotics and Probiotics)
Show Figures

Figure 1

Back to TopTop