Search Results (398)

Background: Diabetes mellitus is associated with worse outcomes after cardiac arrest. Hyperglycemia, diabetes treatments and other long-term sequalae may contribute to this association. We sought to determine the acute effect of diabetes on the return of spontaneous circulation (ROSC) and post-arrest cardiac function in a rat cardiac arrest model. Methods: Eighteen male Wistar rats were utilized, and 12 underwent the induction of type II diabetes for 10 weeks through a high-fat diet and the injection of streptozotocin. The carotid artery flow and femoral arterial pressure were measured. Seven minutes of asphyxial cardiac arrest was induced. An external cardiac compression was performed via an automated piston. Post-ROSC, epinephrine was titrated to a mean arterial pressure (MAP) of 70 mmHg. Data was analyzed using the Mann–Whitney test. The significance was set at p ≤ 0.05. Results: The rate of the ROSC was significantly lower in animals with diabetes, 50% compared to 100% in non-diabetics. Additionally, it took significantly longer to achieve the ROSC in diabetics, p = 0.034. In animals who survived, the cardiac function was reduced, as indicated by an increased epinephrine requirement, p = 0.041, and a decreased cardiac output at the end of the experiment, p = 0.017. The lactate, venous and arterial pressures, heart rate and carotid flow did not differ between groups at 2 h. Conclusions: Diabetes negatively affects the survival from cardiac arrest. Here, the critical difference was the rate of the conversion to a life-sustaining rhythm and the achievement of the ROSC. The post-ROSC cardiac function was depressed in diabetic animals. Interventions targeted at improving defibrillation success may be important in diabetics. Full article

The balance between physiological, psychological, and environmental factors often shapes human experience. In recent years, research has drawn attention to the gut microbiota as a significant contributor to brain function and emotional regulation. This narrative review examines how changes in gut microbiota may relate to depression. We selected studies that explore the link between intestinal dysbiosis and mood, focusing on mechanisms such as inflammation, vagus nerve signaling, HPA axis activation, gut permeability, and neurotransmitter balance. Most of the available data come from animal models, but findings from human studies suggest similar patterns. Findings are somewhat difficult to compare due to differences in measurement procedures and patient groups. However, several microbial shifts have been observed in people with depressive symptoms, and trials with probiotics or fecal microbiota transplant show potential. These results remain limited. We argue that these interventions deserve more attention, especially in cases of treatment-resistant or inflammation-driven depression. Understanding how the gut and brain interact could help define clearer subtypes of depression and guide new treatment approaches. Full article

The gut microbiota and its interaction with the nervous system through the gut–brain axis (MGB) have been the subject of growing interest in biomedical research. It has been proposed that modulation of microbiota using probiotics could offer a promising therapeutic alternative for mood regulation and the treatment of anxiety and depression disorders. The findings indicate that several probiotic strains, such as Lactobacillus and Bifidobacterium, have demonstrated anxiolytic and antidepressant effects in pre and clinical studies. These effects seem to be mediated by the regulation of the hypothalamic–pituitary–adrenal axis (HPA), the synthesis of neurotransmitters such as serotonin (5-HT) and Gamma-amino-butyric acid (GABA), as well as the modulation of systemic inflammation. However, the lack of standardization in dosing and strain selection, in addition to the scarcity of large-scale clinical studies, limit the applicability of these findings in clinical therapy. Additional research is required to establish standardized therapeutic protocols and better understand the role of probiotics in mental health. The aim of this narrative review is to discuss the relationship between the gut microbiota and the MGB axis in the context of anxiety and depression disorders, the underlying neurobiological mechanisms, as well as the preclinical evidence for the effect of probiotics in modulating these disorders. In this way, an exhaustive search was carried out in scientific databases including PubMed, ScienceDirect, Scopus, and Web of Science. Preclinical research evaluating the effects of different probiotic strains in animal models during chronic treatment was selected, excluding those studies that did not provide access to the full text. Full article

Clinical and animal studies suggest that multiple brain systems are involved in mediating reward-motivated and related emotional behavior including the consumption of commonly used drugs and palatable food, and there is evidence that the repeated ingestion of or exposure to these rewarding substances may in turn stimulate these brain systems to produce an overconsumption of these substances along with co-occurring emotional disturbances. To understand this positive feedback loop, this review focuses on a specific population of hypothalamic peptide neurons expressing melanin-concentrating hormone (MCH), which are positively related to dopamine reward and project to forebrain areas that mediate this behavior. It also examines neurons expressing the peptide hypocretin/orexin (HCRT) that are anatomically and functionally linked to MCH neurons and the molecular systems within these peptide neurons that stimulate their development and ultimately affect behavior. This report first describes evidence in animals that exposure in adults and during adolescence to rewarding substances, such as the drugs alcohol, nicotine and cocaine and palatable fat-rich food, stimulates the expression of MCH as well as HCRT and their intracellular molecular systems. It also increases reward-seeking and emotional behavior, leading to excess consumption and abuse of these substances and neurological conditions, completing this positive feedback loop. Next, this review focuses on the model involving embryonic exposure to these rewarding substances. In addition to revealing a similar positive feedback circuit, this model greatly advances our understanding of the diverse changes that occur in these neuropeptide/molecular systems in the embryo and how they relate, perhaps causally, to the disturbances in behavior early in life that predict a later increased risk of developing substance use disorders. Studies using this model demonstrate in animals that embryonic exposure to these rewarding substances, in addition to stimulating the expression of peptide neurons, increases the intracellular molecular systems in neuroprogenitor cells that promote their development. It also alters the morphology, migration, location and neurochemical profile of the peptide neurons and causes them to develop aberrant neuronal projections to forebrain structures. Moreover, it produces disturbances in behavior at a young age, which are sex-dependent and occur in females more than in males, that can be directly linked to the neuropeptide/molecular changes in the embryo and predict the development of behavioral disorders later in life. These results supporting the close relationship between the brain and behavior are consistent with clinical studies, showing females to be more vulnerable than males to developing substance use disorders with co-occurring emotional conditions and female offspring to respond more adversely than male offspring to prenatal exposure to rewarding substances. It is concluded that the continued consumption of or exposure to rewarding substances at any stage of life can, through such peptide brain systems, significantly increase an individual’s vulnerability to developing neurological disorders such as substance use disorders, anxiety, depression, or cognitive impairments. Full article

In the last several decades, a number of animal models of neurological diseases have been proposed and validated to one degree or another. This review focuses on the olfactory bulbectomized rodent as a model of major depression, a disorder that, because of its prevalence, has been called the “common cold” of neurological diseases, though the disability it causes is far more profound. After describing the method, a brief history of this model and the various validity claims made for it are discussed. Though a legion of physiological and biochemical sequelae of bulbectomy and other animal models of depression have been reported, the focus of this review is behavioral. Therefore, the neurochemical and molecular aspects of the depression models mentioned in this review will not be explored in depth. Lastly, unresolved questions posed by the bulbectomy model are considered along with its utility in the study of other neurological diseases and its future prospects. Full article

Background/Objectives: Neuronal oscillations play a key role in the symptoms of Parkinson’s disease (PD). This study investigates the effects of random synaptic inputs, their correlations, and the interaction with synaptic dynamics and spike timing-dependent plasticity (STDP) on the membrane potential and firing patterns of subthalamic nucleus (STN) neurons, both in healthy and PD-affected states. Methods: We used a modified Hodgkin–Huxley model with a Langevin stochastic framework to study how synaptic conductance, random input fluctuations, and STDP affect STN neuron firing and membrane potential, including sensitivity to refractory period and synaptic depression variability. Results: Our results show that random inputs significantly affect the firing patterns of STN neurons, both in healthy cells and those with PD under DBS treatment. STDP, along with random refractory periods and fluctuating input currents, increases the irregularity of inter-spike intervals (ISIs) in output neuron spike trains. Sensitivity analyses highlight the key role of synaptic depression and refractory period variability in shaping firing patterns. Combining random inputs with STDP boosts the correlation between neuron activities. Furthermore, at fixed input noise levels, the model’s output closely matches experimental firing rate and ISI variability data from PD patients and animals, with statistical tests confirming significant effects of STDP on firing regularity. Conclusions: The findings suggest that the stochastic dynamics of STN neurons, combined with STDP, are crucial for shaping neuronal firing patterns in both healthy and PD-affected states. These insights improve our understanding of how noise and plasticity contribute to neural function and dysfunction, with implications for PD symptom management. Full article

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

Behavioral stress is a recognized triggering factor for systemic diseases, including psychiatric disorders. The stress response is subjected to circadian regulation and many factors shape the susceptibility to its maladaptive consequences, including the biological sex. Accordingly, circadian dysregulation of the stress response, often occurring in a sexually dimorphic manner, is typically associated with psychiatric disorders. However, the interaction between stress, sex, circadian phases, and behavior is still largely unknown. Here, we used the chronic restraint stress (CRS) model in male and female mice to assess the impact of sex and circadian phases on the behavioral consequences of chronic stress. Animals were stressed either in the light or dark phase, and anxious-/depressive-/anhedonic-like behaviors were assessed. Associated transcriptional changes in clock genes were measured in the prefrontal cortex. A significant interaction of stress, sex, and circadian phase was found in most of the parameters evaluated, with no behavioral response to stress in males stressed in the dark phase, and an exaggerated response in females stressed in the dark phase compared to the light phase. We also found some molecular changes in corticosterone serum levels and expression of clock genes in the prefrontal cortex. Full article

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

Anxiety disorders, as common neurological diseases in clinical practice, often coexist with depression. Epidemiological surveys indicate that approximately 85% of patients with depression exhibit significant anxiety symptoms. This comorbid state not only exacerbates clinical symptoms but also leads to treatment resistance and prolonged disease duration. This study innovatively developed a compound aromatic plant essential oil (EO) formulation with remarkable anxiolytic and antidepressant effects and systematically elucidated its mechanism of action. The study found that the essential oil formulation, administered via inhalation, could significantly improve behavioral abnormalities in animals subjected to the chronic unpredictable mild stress (CUMS) model, specifically manifesting as (1) the reversal of stress-induced weight gain retardation; (2) a significant increase in sucrose preference; (3) an increase in the total distance of spontaneous activity; and (4) the prolongation of exploration time in the open arms of the elevated plus maze. Neuropathological examinations confirmed that the formulation could effectively protect the structural integrity of hippocampal neurons and alleviate CUMS-induced neural damage. In terms of mechanism of action, the study revealed that the formulation regulates the neurotransmitter system through multiple targets: (1) the upregulation of serotonin (5-HT) and γ-aminobutyric acid (GABA) levels; (2) the downregulation of glutamate (GLU) concentration; and (3) key targets identified via network pharmacological analysis, such as ESR1, STAT3, and PPARG. These findings provide molecular-level evidence for understanding the neuromodulatory effects of aromatic essential oils. Pharmaceutical formulation studies showed that the oil-in-water (O/W) type compound essential oil microemulsion, prepared using microemulsification technology, has a uniform particle size and excellent stability, maintaining stable physicochemical properties at room temperature for an extended period, thus laying a foundation for its clinical application. This study not only validates the practical value of traditional medicine but also provides new ideas for the development of novel anxiolytic and antidepressant drugs, achieving an organic integration of traditional experience and modern technology. Full article

Tactical athletes and military personnel engaged in intense exercise need to consume enough quality protein in their diet to maintain protein balance and promote recovery. Plant-based protein sources contain fewer essential amino acids (EAAs), while pork loin contains a higher concentration of EAAs and creatine than most other animal protein sources. This study aimed to determine whether the ingestion of plant-based or pork-based military-style meals ready-to-eat (MREs) affects recovery from and subsequent Army Combat Fitness Test (ACFT) performance. Methods: Twenty-three (n = 23) University Corps of Cadets members participated in a randomized, double-blind, placebo-controlled, and crossover-designed study. Diets were prepared by a dietitian, food scientist, and chef to have similar taste, appearance, texture, and macronutrient content. The chef also labeled the meals for double-blind administration. Participants refrained from intense exercise for 48 h before reporting to the lab in a fasted condition with a 24 h urine sample. Participants donated a blood sample, completed questionnaires and cognitive function tests, and consumed a pre-exercise meal. After four hours, participants performed the ACFT according to military standards. Participants were fed three MREs daily while returning to the lab in a fasted condition at 0600 with 24 h urine samples after 24, 48, and 72 h of recovery. On day 3, participants repeated the ACFT four hours after consuming an MRE for breakfast. Participants resumed normal training and returned to the lab after 2–3 weeks to repeat the experiment while consuming the alternate diet. Data were analyzed using general linear model statistics with repeated measures and percent changes from baseline with 95% confidence intervals. Results: Results revealed that 3 days were sufficient for participants to replicate ACFT performance. However, those consuming the pork-based diet experienced less muscle soreness, urinary urea excretion, cortisol, inflammation, and depression scores while experiencing a higher testosterone/cortisol ratio and appetite satisfaction. There was also evidence of more favorable changes in red and white blood cells. Conversely, blood lipid profiles were more favorably changed when following a plant-based diet. Conclusions: These findings suggest that protein quality and the availability of creatine in the diet can affect recovery from intense military-style exercise. Minimally, plant-based MREs should include 6–10 g/d of EAA and 2–3 g/d of creatine monohydrate to offset dietary deficiencies, particularly in military personnel following a vegetarian diet. Registered clinical trial #ISRCTN47322504. Full article

Chronic stress can lead to nervous system dysfunction and depression-like behaviors in animals. Gypenosides can improve chronic stress-induced neuronal damage, but the protective mechanism remains poorly understood. This study aims to investigate the effect and mechanism of gypenosides on chronic stress-induced neuronal ferroptosis. Therefore, we established a chronic stress-induced neuronal damage model in vitro using corticosterone to induce PC12 cell injury. We demonstrated that ferroptosis inhibitors DFO and Ferrostatin-1 alleviated corticosterone-induced cell death in PC12 cells by reducing iron accumulation, lipid peroxidation, and increasing cell viability. Meanwhile, gypenosides attenuated ferroptosis agonist Erastin-induced ferroptosis in PC12 cells. Then, gypenosides ameliorated corticosterone-induced ferroptosis in PC12 cells. In terms of molecular mechanisms, gypenosides decreased the expression of Hepcidin and DMT1, and increased the expression of Ferritin and FPN1, thereby improving corticosterone-induced iron homeostasis disorders and iron accumulation. Moreover, gypenosides improved corticosterone-induced lipid peroxidation by inhibiting GLS2 expression, upregulating the expression of SLC7A11 and glutathione peroxidase 4, and reducing glutamate accumulation and GSH depletion. Gypenosides also reduced corticosterone-induced release of inflammatory cytokines, the expression of TNFR1, and the phosphorylation of NF-κB and p53 in PC12 cells. These findings indicate that gypenosides attenuate corticosterone-induced ferroptosis by inhibiting TNF-α/NF-κB signaling pathway in PC12 cells. Full article

Background and Objectives: Depression is a multifactorial mental health disorder involving inflammation, oxidative stress, neuroplasticity deficits, and metabolic dysfunction. Emerging research suggests that vitamin K, beyond its classical roles in coagulation and bone metabolism, may influence neurobiological processes relevant to mood regulation. This systematic review evaluates the association between vitamin K and depressive symptoms and explores potential underlying mechanisms. Materials and Methods: A systematic search was conducted across PubMed, Scopus, Cochrane Library, ScienceDirect, and Google Scholar, following PRISMA 2020 guidelines. Eligible studies included human or animal research examining associations between vitamin K status (dietary intake or serum levels) and depression-related outcomes. Fourteen studies met the inclusion criteria: eleven observational studies, one randomized controlled trial (RCT), and two preclinical animal studies. Results: Most observational studies reported an inverse association between vitamin K intake or serum levels and depressive symptoms across diverse populations. One small RCT demonstrated modest improvements in depression scores following vitamin K2 (menaquinone-7) supplementation in women with polycystic ovary syndrome. Two preclinical studies using non-depression models reported behavioral improvements and reduced oxidative stress following vitamin K2 administration. Conclusions: While preliminary findings suggest a potential role for vitamin K in pathways relevant to depression, the current evidence is limited by cross-sectional designs, lack of isoform-specific analyses, and the absence of depression-focused preclinical models. Mechanisms including inflammation reduction, oxidative stress modulation, sphingolipid regulation, and vitamin K-dependent protein signaling (e.g., GAS6 and osteocalcin) were discussed based on indirect evidence and require further investigation in depression-specific contexts. Full article

Background: In addition to behavioral and biochemical abnormalities, a parafunction associated with temporomandibular joint disorders (TMDs) resulted in stress-induced depression in rats. Exploring how chronic stress influences molar wear in rodents provides insights into the understanding of depression, TMD, and oral health. This study aimed to conduct a three-dimensional (3D) analysis of first molar wear in an animal model of depression by comparing molar attrition and cusp variation between stressed male rats and control groups. Methods: After obtaining a validated model of depression in male rats, we obtained 3D scans of lower molars to analyze wear patterns. The 3D analysis was applied to quantify cusps’ volume and the difference in first molar cusp morphological structure. The data were then compared to identify significant morphological differences between groups side by side. Results: The analysis revealed the reduction of cusps’ volume in the depression groups. Rats exposed to depression exhibited significantly greater occlusal table wear than their control counterparts (p < 0.05). Conclusions: As dentistry moves towards greater digital imaging, understanding the impact of psychological factors on TMD becomes increasingly necessary. This study shows that stress-induced depression in rats can result in significant tooth wear, as investigated using a 3D dental scanner. Full article

Non-alcoholic fatty liver disease (NAFLD) has been associated with depression and inadequate response to antidepressants. While ketamine has demonstrated efficacy in treating depression, its impact on pre-existing liver injury and depression remains unclear. This study aimed to evaluate the effects of ketamine treatment in a murine model of depression and liver damage, considering age-related differences. Young and aged male C57BL/6N mice were submitted to chronic unpredictable mild stress (CUMS) and methionine–choline-deficient (MCD) diet to induce depressive-like behavior and NAFLD. Behavioral testing (sucrose preference test, open field test, novel object recognition test, Crawley’s sociability test) were used to assess ketamine’s (50 mg/kg) effect on behavior. Hepatic ultrasonography was utilized to evaluate liver status. The cortical and hippocampal NeuN+, GFAP+, and Iba1+ signals were quantified for each animal. Ketamine administration proved effective in relieving anhedonia and anxiety-like behavior, regardless of liver damage. Although ketamine treatment did not improve memory in animals with liver damage, it enhanced sociability, particularly in aged subjects. The acute administration of ketamine did not affect the severity of liver injury, but seems to affect astrogliosis and neuronal loss. Although animal models of depression only replicate certain clinical features of the condition, they remain valuable for evaluating the complex and varied effects of ketamine. By applying such models, we could demonstrate ketamine’s therapeutic versatility, and also indicate that responses to the treatment may differ across different age groups. Full article