Search Results (193)

As a traditional element of Chinese medicine, Hippocampus erectus is well known for promoting adolescent growth, yet its active fractions and underlying molecular mechanisms remain unclear. In this study, the aqueous extract of H. erectus was subjected to in vitro simulated gastrointestinal digestion and ultrafiltration to separate three molecular weight fractions (<10 kDa, 10–30 kDa, >30 kDa). Their chemical profiles were characterized, and osteogenic activities were systematically evaluated using cell assays, a juvenile rat model, and integrated transcriptomics and data-independent acquisition (DIA) proteomics. Results revealed that chemical profiling showed the >30 kDa fraction was mainly composed of hemocyanin subunits, and the 10–30 kDa fraction was enriched in growth-related amino acids and steroid derivatives; functionally, the 10–30 kDa fraction promoted preosteoblast proliferation and early differentiation via enhanced alkaline phosphatase (ALP) activity, while the >30 kDa fraction dominated late osteoblast maturation and mineralization. Both fractions significantly increased rat body and bone length by expanding growth plate proliferative zones and elevating serum insulin-like growth factor-1 (IGF-1)/bone morphogenetic protein-2 (BMP-2) levels. Transcriptomic and proteomic analyses identified vascular endothelial growth factor (VEGF), Wingless-related integration site (Wnt), phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt), and extracellular matrix (ECM)–receptor interaction as potential core regulatory pathways. Integrated multi-omics analysis further confirmed Frizzled-related protein B (Frzb) and AKT1 substrate 1 (Akt1s1) as candidate key regulatory targets enriched in the Wnt and adenosine monophosphate-activated protein kinase (AMPK) signaling pathways. These findings elucidate the multi-fraction, multi-pathway mechanism of H. erectus in promoting skeletal development, providing scientific evidence for its traditional use and a theoretical basis for growth-promoting functional food development. Full article

Background: Prenatal cannabinoid exposure (PCE) causes neurodevelopmental impairments affecting learning and memory; however, the receptor-level interactions underlying these cognitive deficits remain poorly understood. This study investigated whether a moderate dose of prenatal Δ⁹-tetrahydrocannabinol (THC) exposure alters the biophysical properties of synaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which are critical mediators of excitatory neurotransmission and synaptic plasticity. Methods: Pregnant Sprague-Dawley rats received a moderate dose (5 mg/kg) of THC or vehicle control via oral gavage throughout gestation and early postnatal development. Single-channel electrophysiological activity of the AMPA receptors (AMPARs) was recorded using patch-clamp techniques on synaptosomal AMPARs reconstituted into artificial lipid bilayers from adolescent offspring. Western blot analysis of GluA1- and GluA2-containing AMPAR subunits and the postsynaptic scaffold protein postsynaptic density 95 (PSD95) was conducted to assess protein levels. Results: Prenatal THC exposure decreased AMPAR open-channel probability, reduced mean open time, increased mean closed time, and altered burst channel activity significantly, without altering GluA1, GluA2, or PSD95 protein levels. Furthermore, the interactive channel-gating activity observed in control synaptosomes was absent in synaptosomes derived from THC-exposed offspring. Conclusions: Prenatal cannabinoid exposure induces early alterations in glutamatergic synaptic function primarily mediated by changes in AMPAR channel kinetics rather than receptor abundance. By identifying AMPAR single-channel dysfunction as a sensitive marker of PCE-induced synaptic disruption, this work provides a mechanistic framework linking prenatal THC exposure to long-term alterations in learning and memory. Full article

Prenatal stress (PNS) predisposes individuals to mental disorders later in life. Adolescence is a period of heightened brain plasticity and vulnerability, when many mental disorders emerge, yet pharmacological strategies remain largely underexplored. In adult PNS rats, lurasidone (LUR) has been shown to reduce PNS-induced risk; however, its effects following adolescent administration remain unclear. To investigate the long-lasting effects of PNS and their modulation following sub-chronic LUR adolescent treatment, a whole-genome expression analysis of the prefrontal cortex (PFC) of adult male PNS rats was performed. Twelve PNS and eleven control rats were randomly assigned to receive vehicle or LUR from postnatal day (PND) 35 to 49 and sacrificed at PND 50. Partek Genomics Suite and Ingenuity Pathway Analysis were used for differential expression and pathway analyses. Within the PFC, PNS induced an upregulation of pathways involved in environmental information processing and in immune system-related pathways, which was reduced after LUR, as observed by IL-8 signaling (z-scores before: 1.34 and after LUR: −2.65). In parallel, LUR administration itself modulated Inositol-related metabolic pathways. Overall, these findings suggest that LUR adolescent treatment may counteract some PNS-induced alterations, supporting adolescence as a critical window for early preventive strategies with translational relevance for stress-related neuropsychiatric disorders. Full article

Background/Objectives: The study investigated the potential of mixed fruits and berries (MFB) as a dietary intervention to mitigate cafeteria (CAF) diet-induced gut microbiome dysbiosis and hepatic dysfunction associated with metabolic syndrome and steatohepatitis (MASH) in an adolescent rat model. Methods: Forty-eight adolescent male Sprague-Dawley rats (n = 3 cages per group (two rats per cage)) were divided into eight experimental groups, where NC received the normal AIN-93G basal diet, PC received the CAF diet and normal AIN-93G basal diet, T₁ and T₂ received MFB supplementation (3% and 6% levels) without CAF exposure, P₁ and P₂ received a MFB (3% and 6% levels) supplementation initiated at the onset of CAF feeding, and I₁ and I₂ received MFB supplementation initiated 2 weeks after CAF feeding. After 6 weeks, cecal 16S rRNA, hepatic histopathology, Oil Red O staining, and metabolic dysfunction-associated steatotic liver disease (MASLD)-related biomarkers (liver enzymes, alanine aminotransferase (ALT), and aspartate aminotransferase (AST)) were analyzed. Results: AST: ALT ratio was the highest in the PC group (3.63, p < 0.05) compared to the MFB groups. Oil Red O staining showed lower hepatic lipid accumulation, and histological analysis demonstrated a marked reduction in portal inflammatory cell infiltration in MFB. Alpha diversity (Simpson Index) decreased in PC (Kruskal–Wallis, p = 0.043). CAF increased Lactobacillus johnsonii (+75%, p < 0.05), while reducing L. murinus and L. intestinalis (~90%, p < 0.05). MFB supplementation restored Bifidobacterium Pseudolongum and increased Akkermansia muciniphila levels in the P₂, I₁, and I₂ groups (~20-fold, p < 0.05). Bacteroides dorei was present in all groups except the PC group. These bacteria presented a positive correlation with key SCFAs. Conclusions: The results from this study indicated that MFB supplementation modulated gut microbiota composition and enhanced SCFA production, thereby strengthening intestinal barrier integrity and reducing gut-derived inflammation. Collectively, these effects attenuated hepatic lipid accumulation and inflammation, highlighting the potential of MFB to restore gut–liver axis homeostasis disrupted by CAF-induced dysbiosis in adolescent rats. Full article

The cannabinoid 1-receptor (CB1R) is found in particularly high levels in the hippocampus (HPC). Increased CB1R density and binding are observed in patients with schizophrenia, and epidemiological studies suggest that regular cannabis use during adolescence is a risk factor for the disease. CB1R was shown to interfere with neuronal network oscillations and to impair sensory gating and memory function. Neuronal oscillations are essential in multiple cognitive functions, and their impairment was documented in neurological and psychiatric diseases. The aim of this study was to investigate how adolescent pre-treatment with the CB1R-selective agonist CP-55940 may lead to abnormalities in theta synchronization in adulthood. Rats were pre-treated with CP-55940 or vehicle during adolescence (daily injections in PND 32–36 or PND 42–46). They were then tested in adulthood (PND over 70) under urethane anesthesia. Hippocampal theta rhythm was elicited by brainstem stimulation at five intensity levels 1 hour before and up to 5 h after injection. We found a significant decrease in elicited theta power after CP-55940 in adult rats, which was aggravated further in rats pre-treated in adolescence with the CB1R agonist. The effect was significantly larger in rats pre-treated during early adolescence (PND 32–36) compared to the group pre-treated during late adolescence (PND 42–46). We conclude that (1) exposure to cannabis during adolescence leads to increased sensitivity to CB1R agonist in adulthood, and (2) early adolescence, a critical period for development of HPC networks generating theta rhythms, is particularly prone to this sensitivity. Full article

Acquiring new experiences, especially in adolescence, shapes behavioral responses to life’s challenges. The absence of novelty-related experiences in laboratory rats raises concerns about their behavioral development and the reproducibility of research. This study examined changes in behavioral responses to novelty from early and late adolescence to adulthood, as well as the long-term effects of prior novelty exposure. To assess maturational differences, seven early adolescent, nine late adolescent, and seven adult male Wistar Han rats were tested once in a behavioral battery consisting of the novel arena, novel object exploration, light/dark box, and elevated plus maze. To evaluate the influence of prior experience, early and late adolescent groups were retested once more in adulthood. Late adolescents showed consistent patterns across spatial tasks, displaying increased anxiety-like behavior and reduced exploratory and risk-assessment activity. Early adolescents exhibited variable behaviors, resembling adult or late adolescent profiles depending on the task. Novelty exposure during adolescence produced subtle long-term effects, including reduced discomfort in mildly aversive environments, while late adolescent experience increased thigmotaxis in adulthood. Overall, adolescent responses to novelty were influenced more by spatial than nonspatial environmental features. These findings highlight stage-specific sensitivity to novelty, the influence of adolescent experience, and the potential reuse of experienced animals. Full article

Alcohol’s chronic neurotoxic and degenerative effects mediate alcohol-related brain damage (ARBD), which is marked by neurobehavioral, cognitive, and motor deficits. Major underlying abnormalities include impairments in signaling through the insulin and insulin-like growth factor (IGF) pathways, which regulate energy metabolism. This study examined the potential role of dysregulated incretin network-related mechanisms as mediators of ARBD and evaluated a non-invasive serum exosome (S-EV)-based approach for detecting brain abnormalities. Frontal lobe tissue and S-EVs isolated from Long–Evans adolescent rats maintained for 2 weeks on control or 24% ethanol (caloric) containing liquid diets (n = 8/group) were analyzed using multiplex magnetic bead-based enzyme-linked immunosorbent assays (ELISAs). ARBD was associated with significantly reduced insulin, C-peptide, glucagon, ghrelin, leptin, GIP, and amylin levels in the frontal lobe and/or S-EV samples. In contrast, chronic ethanol exposure had no significant effects on PP, PYY, or GLP-1, and it did not increase proinflammatory cytokine expression. Chronic ethanol feeding broadly affected (primarily inhibiting) the expression of metabolic hormones linked to insulin/IGF signaling. The reductions in GIP and amylin suggest potential targets for therapeutic intervention to enhance brain energy metabolism via insulin networks. On the other hand, the findings suggest that GLP-1 receptor agonists may have limited efficacy in remediating the effects of ARBD. Finally, the results support the use of non-invasive S-EV assays to detect and guide treatment for metabolic brain dysfunction in ARBD. Full article

Nicotinamide adenine dinucleotide (NAD⁺) serves as a critical cofactor in redox reactions and metabolic transformations catalyzed by NAD-dependent enzymes and is essential for bacterial survival and virulence. The biosynthesis of NAD⁺ in the cariogenic pathogen Streptococcus Sobrinus (S. sobrinus), a pivotal participant in oral cavities of children and adolescents with a history of caries, has yet to be explored. Bioinformatics, genetics, and biochemical techniques were used to identify NAD⁺ biosynthesis pathways and corresponding regulator in S. Sobrinus. S. sobrinus lacks de novo NAD⁺ synthesis pathway but comprises NA and Nam salvage pathway I (PncA-PncB-NadD-NadE) and PnuC-NadR salvage pathway III. NiaY and PnuC were involved in the salvage pathways. N-terminal domain of SsNrtR regulator was identified as DNA-binding domain binding to the pnuC and pncB probe, and addition of ADP-ribose reversed the binding of SsNrtR to the target promoters to regulate NAD⁺ salvage pathways. C-terminal domain of SsNrtR was non-catalytic, consistent with loss of Nudix motif conservation. Furthermore, the abrogation of niaR compromised multiple pathogenic traits, including cellular proliferation, acidogenesis, and the architecture/mechanical integrity of biofilms. Consequently, this mutant exhibited attenuated virulence in a rat caries model. Our findings conclusively demonstrate that SsNrtR-mediated regulation of NAD⁺ homeostasis is a critical determinant of the cariogenic potential of S. sobrinus. This study identifies SsNrtR as a previously uncharacterized NAD⁺-responsive regulator that integrates metabolic homeostasis with the control of virulence in Streptococcus sobrinus. These findings elucidate a novel metabolic–virulence regulatory axis in this species and position SsNrtR as a promising target for the development of anti-caries interventions. Full article

Binge drinking is defined as consuming a large amount of alcohol in a short period of time, whereas hangover is a cluster of unpleasant mental symptoms and physical signs that typically manifest the next day after binge drinking. Binge drinking is a prevalent pattern of alcohol consumption, especially in adolescents, with dualistic effects on social behavior. While some studies demonstrate that a single episode of binge drinking enhances sociability and preference for social novelty, other studies indicate that repeating cycles of binge drinking and hangover can lead to persistent negative affect and consequently social withdawal. This is an integrative narrative review synthesizing human studies and animal models of binge drinking (also known as alcohol intoxication) and hangover (also known as alcohol withdrawal). The major databases consulted were PubMed, Scopus, and Web of Science. The search terms used were “binge drinking” or “hangover”and “social behavior” or “social brain” in combination with “rats”, “mice” or “humans”. Finding the missing link between structural and functional changes in the social brain in the context of binge drinking and hangover is crucial for developing novel therapeutic strategies for alcohol intoxication and withdrawal. This review focuses on changes in hypothalamic neurohormones and extrahypothalamic neurotransmitters in these states, and concludes with the statement that targeting neuropeptides such as corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP) and their receptors, which are involved in both binge drinking and social behavior, may prevent repeated cycles of binge drinking and hangover from spiraling into alcohol addiction and, ultimately, social isolation. Full article

Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with neurodevelopmental toxicity, yet the effects of exposure during adolescence and adulthood remain underexplored. This scoping review evaluates the neurotoxic outcomes of post-weaning PCB exposure in rodent models. A comprehensive literature search was conducted across PubMed, Embase, and Scopus. Studies were screened according to PRISMA guidelines. Articles were included if they reported neurotoxic or behavioral outcomes in mice or rats exposed to PCBs during post-weaning stages. Thirty-five studies met the inclusion criteria, encompassing a variety of PCB congeners and mixtures administered via oral, inhalation, or intraperitoneal routes. Reported neurotoxic outcomes included histological and morphological brain changes, oxidative stress, disrupted calcium signaling, altered neurotransmitter systems, apoptosis, and gene expression alterations. These outcomes were assessed using diverse methodological approaches, including immunohistochemistry, biochemical assays, and gene expression profiling. Behavioral outcomes affected by PCB exposure included locomotion, anxiety-like behavior, learning and memory, motor coordination, and cognitive flexibility. Effects were often exposure-specific and sex-dependent, with limited female-focused studies and integrative molecular-behavioral assessments. These findings highlight the broad neurotoxic potential of PCBs following adolescent or adult exposure and underscore the need for further mechanistic, sex-specific research to inform health risk assessment and regulatory policy. Full article

Malnutrition during adolescence can cause metabolic diseases later in life. This study examined the short- and long-term effects of undernutrition during adolescence on body composition, glucose homeostasis and redox balance. Male (n = 32) and female (n = 32) Wistar rats were fed a rodent chow reduced by 50% (FR50) of the amount consumed by control rats (CONT) from 30 to 60 days and then fed ad libitum until 120 days of age. Half of the rats were euthanized at 60 and the other half at 120 days old. At 60 and 120 days old, glucose and insulin tolerance test; skeletal muscle, visceral fat, liver and interscapular brown adipose tissue (iBAT) weights; and oxidative stress marker levels in the liver and iBAT were evaluated. The FR50 male (FR50-M) and female (FR50-F) rats exhibited a lean phenotype and high insulin sensitivity at 60 days of age (p < 0.05), but at 120 days of age, they exhibited an obese phenotype with high insulin sensitivity (p < 0.05). An increase in liver GSH was observed as only a short-term effect (p < 0.05). At 120 days of age, only male rats displayed increased iBAT GSH levels (p < 0.05) and reduced CAT activity (p < 0.01). In summary, undernutrition during adolescence affects body composition, glucose homeostasis and redox status equally in males and females but causes long-term impairment of the redox status of iBAT only in male rats. Full article

The response of the hypothalamic–pituitary–thyroid (HPT) axis to energy demands is perturbed by previous chronic stress perceived during the neonatal or adult periods. We examined the effects of chronic variable stress (CVS) during adolescence on the responses of the HPT axis and target tissues of adult rats to 14 days of voluntary wheel running (Ex) or pair-feeding (PF) to match the reduced food intake of exercised rats. CVS increased the expression of Gr in the paraventricular nucleus (PVN) and of Npy in the mediobasal hypothalamus (MBH) in males; serum corticosterone concentration increased (1.5×), MBH Dio2 and PVN Trh decreased (40%) in both sexes, serum fT4 increased only in males, while T3 and fT3 increased (2×) in females. Exercise decreased Cort and increased PVN Trh expression only in males. In both sexes, it increased MBH Pomc and Dio2 (2×), skeletal muscle Dio2 and Pgc1a (2×), inguinal and perigonadal white adipose tissue (WAT) Adrb3, Dio2, Pparg, Hsl (1.5×), and brown adipose tissue Adrb3, Dio2, and Ucp1. All exercise-induced changes were repressed in CVS-Ex, except Hsl in inguinal WAT of both sexes, or BAT Dio2 in females, which, in contrast, was stimulated (1.5×). PF had lower values than sedentary in most parameters. These results support the idea that adolescent stress affects adult metabolic and neuroendocrine responses to exercise in a sex-specific manner. Full article

The bed nucleus of the stria terminalis (BNST) is a heterogeneous and complex limbic forebrain structure, which plays an important role in drug addiction and anxiety. Dynorphin and kappa-opioid receptors (DYN/KOR) comprise a crucial neural system involved in modulating stress-induced drug and alcohol addiction. Previous studies have highlighted the BNST as a brain region with a strong DYN/KOR expression. However, no research has been conducted on the adolescent plasticity of this system. In the present study, we used 20- and 60-day-old Wistar rats to reveal the adolescent dynamics and possible sex differences of the DYN/KOR system in certain BNST nuclei associated with addiction behavior. We found a low expression of DYN in neuronal perikarya and a significant increase in DYN-containing nerve fibers in the lateral posterior and lateral dorsal nuclei of the rat BNST. In addition, an enhanced expression of KORs was observed in the examined BNST subnuclei with some sex differences favoring females, thus highlighting the importance of considering critical developmental differences between sexes in research. The dynamics of the DYN/KOR system observed in this study may help to explain the increased vulnerability of adolescents for developing drug and alcohol addiction. Full article

Background/Objectives: The hippocampus is an essential part of the central nervous system (CNS); it plays a significant role in social–cognitive memory processing. Prenatal exposure to valproic acid (VPA) can lead to impaired hippocampal functions. In this study, we evaluated the effect of plumbagin (PLB) as a natural product on spatial learning and memory, neuro-morphological changes, and inflammation levels in a VPA-induced autism model during adolescence. Methods: Pregnant Wistar rats received a single intraperitoneal (i.p.) injection of VPA (600 mg/kg) or saline on gestational day 12.5. The male offspring were then categorized and assigned to five groups: Saline+DMSO-, VPA+DMSO-, and VPA+PLB-treated groups at doses of 0.25, 0.5, or 1 mg/kg. Spatial learning and memory were evaluated using the Morris water maze. Histopathological evaluations of the hippocampus were performed using Nissl and hematoxylin–eosin staining, as well as immunofluorescence. The pro-inflammatory cytokine levels were also quantified by quantitative real-time PCR. Results: The findings revealed that a VPA injection on gestational day 12.5 is associated with cognitive impairments in male pups, including a longer escape latency and traveled distance, as well as decreased time spent in the target quadrant. Treatment with PLB significantly enhanced the cognitive function, reduced dark cells, and ameliorated neuronal–morphological alterations in the hippocampus of VPA-exposed rats. Moreover, PLB was found to reduce astrocyte activation and the expression levels of pro-inflammatory cytokines. Conclusions: These findings suggest that PLB partly mitigates VPA-induced cognitive deficits by ameliorating hippocampal inflammation levels. Full article

Prenatal cannabis exposure (PCE) has been associated with altered prefrontal cortex (PFC) activity and connectivity in adulthood, potentially increasing the risk of psychopathology later in life. This risk is thought to involve a complex interplay between the endocannabinoid and dopaminergic systems. We investigated the transcriptional regulation of genes associated with these systems in an animal model of PCE during adolescence, focusing on DNA methylation and specific microRNAs (miRNAs). Our study revealed increased mRNA levels of dopamine D1 and D2 receptors (Drd1 and Drd2) in the PFC, with a notable effect on Drd2 in male offspring. Notably, we observed a consistent reduction in Drd2 DNA methylation levels in PCE male rats. Both Drd1 and Drd2 expressions were regulated by selective miRNAs. Accordingly, we found changes in the excitability of PFC pyramidal neurons in male adolescent PCE offspring, along with alterations in the Netrin-1/DCC guidance cue system. Our findings highlight PCE-induced modifications of the PFC dopaminergic system while maintaining stable gene expression of the endocannabinoid system in male offspring. Changes in this complex interaction during sensitive developmental periods like adolescence might lead to sex-dependent divergent behavioral outcomes induced by PCE. Full article