Alzheimer's disease (AD) is a progressive neurodegenerative disease with amyloid-beta (Aβ) plaques, tau tangles, neuroinflammation, and oxidative stress, and it causes cognitive impairment and neuronal loss. The pharmacological treatment is of limited effectiveness, therefore the interest in novel approaches such as intermittent fasting (IF). IF, a nutritional regimen of periodic caloric restriction, has shown a potential to modulate neurodegenerative alterations by metabolic and molecular mechanisms. This review presents the implications of IF in the etiopathogenesis of AD, specifically in controlling brain-derived neurotrophic factor (BDNF). BDNF is a major neurotrophin that plays a key role in synaptic plasticity, neuronal survival, and cognition. Evidence indicates that BDNF is drastically decreased in AD, therefore enhancing disease progression. IF enhances BDNF expression via mechanisms such as improved mitochondrial function, increased ketone body production, and reduced systemic inflammation. Preclinical studies indicate that IF not only upregulates BDNF but also alleviates key AD pathologies, including Aβ deposition and tau hyperphosphorylation. Additionally, clinical data highlight the cognitive benefits of IF and its role in modulating metabolic health, although studies specifically linking IF, BDNF and AD in humans remain limited. This review underscores the need for further research to determine optimal IF protocols and clarify its long-term impact on AD progression. IF's ability to modulate BDNF and other neuroprotective pathways positions it as a promising non-pharmacological intervention for AD management. By bridging metabolic health and neuroprotection, IF offers potential therapeutic synergy for mitigating AD's complex etiopathogenesis.

Associations between sleep disturbance and working memory (WM) vary across tasks and outcome measures. This study examined behavioral and electrophysiological correlates of subjective sleep disturbance during verbal working memory (VWM) and spatial working memory (SWM) in university students. Sixty-one participants were classified using Pittsburgh Sleep Quality Index (PSQI) scores into a sleep disturbance group (n = 28) and a normal sleep group (n = 33) and completed separate verbal and spatial 2-back tasks with event-related potential (ERP) recording. After adjustment for depression, anxiety, and stress, the sleep disturbance group showed lower VWM accuracy (ACC) (mean difference = -3.89 percentage points, 95% CI [-6.83, -0.96]) and discrimination sensitivity (d'). VWM false alarm rates (FAR) were also higher, although the absolute difference was small. Higher PSQI scores were associated with lower VWM ACC and d' and higher FAR. The sleep disturbance group showed lower VWM P3 amplitude averaged across the analyzed electrode sites and longer P3 peak latency at Oz. No significant group-related effects were detected for VWM median reaction time or N2 measures, or for SWM behavioral and ERP measures. These findings link subjective sleep disturbance to lower ACC and discrimination during verbal updating, accompanied by differences in later task-related electrophysiological processing. Future longitudinal and intervention studies with matched tasks and objective sleep measures could clarify the temporal and causal relationships underlying these associations.

Athletes have to cope with psychosocial and physiological stressors, requiring recovery to ensure subsequent performance. According to the undoing-hypothesis, positive emotions (PE) may enhance psychophysiological recovery. The present two studies investigated the undoing hypothesis and its benefits for athletes' cognitive (Study 1; n = 60) and motor (Study 2; n = 30) performance. After a combined psychosocial-physiological stressor, participants either completed a five-minute PE induction (music; imagination exercise) or were assigned to a resting condition. Emotions, perceived stress-recovery, and physiological parameters (e.g., heart rate, heart rate variability, cortisol) were assessed. In Study 1, inhibition and cognitive flexibility were measured once. In Study 2, hand force and jump height were measured using a pre-posttest design. Due to the lack of psychological stress responses and successful PE induction, no conclusions could be drawn regarding the undoing hypothesis. Nevertheless, the present study provides valuable methodological insights into the challenges of testing the undoing hypothesis in athletes. These insights can inform the design and implementation of future studies and thereby contribute to advancing research on the undoing hypothesis in athletic populations.

Anxiety disorder risk is influenced by both adverse environmental factors and genetic background. We previously described high-avoidance animal (HAA) and low-avoidance animal (LAA) strains of male Hatano rats that may provide robust models for assessing interactions between genetic background and environment driving anxiety disorder pathogenesis. We examined the potential of environmental enrichment (EE), a non-pharmacological approach, to suppress trait anxiety disorders by comparing anxiety-related behaviors and physiological metrics between HAA and LAA lines exposed to EE or standard housing. At 4 weeks of age, 10-12 male rats from each strain were assigned to EE or standard conditions. EE for 4-5 weeks significantly (p = 0.0002 by Tukey-Kramer's test) reduced anxiety-related behaviors in LAAs in the elevated plus maze test, but had no similar anxiolytic effect in HAAs. In contrast, EE for 11 weeks significantly (p = 0.0072 by Tukey-Kramer's test) reduced passive avoidance memory retention in HAAs, but not in LAAs. Real-time quantitative PCR revealed upregulated expression of Bdnf exons 1, 3, and 4 in the hippocampus of LAAs following EE, while the same treatment increased the expression of Bdnf exon 3 in the hippocampus of HAAs. Alternatively, EE did not alter mRNA expression levels of the BDNF receptor TrkB and the glucocorticoid receptor in hippocampus, or influence plasma corticosterone, prolactin, and testosterone concentrations. These findings have potential clinical implications for anxiety disorders, suggesting that effects of EE may vary depending on an individual's genetic background and underlying biological characteristics.

Disruptions along the brain-gut-microbiota axis significantly contribute to Alzheimer's disease (AD) pathogenesis. This study evaluated the therapeutic potential of a multi-strain probiotic mixture in mitigating cognitive decline, neuroinflammation, and amyloid pathology in an AD rat model. In the present study, after induction of AD in rats by oral administration of AlCl3 (50 mg/kg) for 28 days, followed by oral treatment with a probiotic mixture (10[9] log CFU/ml) for 42 days. Behavioral assessments were conducted during the final week. Hippocampal tissues were obtained for histopathological and gene expression analyses and fecal samples were subjected to full-length 16S rRNA gene sequencing via Oxford Nanopore approach. Probiotics significantly improved AD-induced deficits in locomotor activity, exploratory behavior, and spatial recognition memory. Histological analysis revealed marked reductions in hippocampal β-amyloid deposition and substantial restoration of colonic mucosal barrier integrity. Microbiota profiling showed that probiotics reversed dysbiosis, significantly enriching beneficial genera (Blautia, Clostridium, Eubacterium). Blautia abundance was strongly negatively correlated with NF-κB expression. Mechanistically, probiotics suppressed neuroinflammation by down-regulating pro-inflammatory cascades TNF-α, NLRP3, IL-1β, and NF-κB activation. Furthermore, treatment suppressed amyloidogenic processing via decreased APP mRNA and enhanced Aβ clearance through upregulation of LRP1 and modulation of AGER. These findings provide integrative evidence that probiotics exert neuroprotective and immunomodulatory effects, supporting their translational potential as a preventive strategy against AD-related cognitive decline.

Parkinson's disease (PD) is a chronic neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and reduced striatal dopamine concentrations. In addition to its characteristic motor manifestations, PD is associated with nonmotor complications, including cardiovascular autonomic dysfunction, orthostatic and postprandial hypotension, and blood pressure instability. The lower prevalence of PD in women has prompted investigation into the potential protective effects of female sex hormones. In this study, we evaluated cardiovascular function, autonomic modulation, cardiac and vascular morphology, and apoptosis in ovariectomized female rats with 6-OHDA-induced parkinsonism treated with estradiol. Wistar rats underwent bilateral ovariectomy and received estradiol (1 mg/kg) or almond oil as the vehicle for 13 consecutive days. Seven days after ovariectomy, 6-OHDA or SHAM vehicle was infused bilaterally into the SNpc. Six days later, the animals underwent femoral artery catheterization, and mean arterial pressure (MAP) and heart rate (HR) were recorded after 24 h. The 6-OHDA lesion reduced striatal dopamine concentrations by more than 50%, confirming the induction of parkinsonism. No significant group differences were detected in MAP, HR, autonomic variability, or baroreflex sensitivity. However, parkinsonism reduced left ventricular wall thickness, increased apoptosis in both ventricles, and decreased cardiac and aortic collagen content. Estradiol increased left ventricular wall thickness and partially attenuated ventricular apoptosis and the parkinsonism-associated alteration in aortic elastin. These findings indicate that 6-OHDA-induced parkinsonism produces cardiac and aortic structural alterations that are not reflected in basal cardiovascular or autonomic measurements and, estradiol may modulate selected cardiac alterations. Although the underlying mechanisms and translational relevance require further investigation, our findings suggest potential clinical relevance for postmenopausal women with Parkinson's disease.

Methamphetamine addiction leads to profound cognitive and emotional impairments through persistent neuroinflammatory and neurodegenerative processes. Recent advances suggest that platelet-derived exosomes possess the potential to promote neurorepair and functional recovery. However, the therapeutic efficacy of exosomes may be influenced by time-of-day administration, given that neural plasticity, blood-brain barrier function, and exosomal dynamics are strongly modulated by diurnal rhythms. Understanding how treatment timing across the daily cycle modulates the neuroprotective and behavioral effects of platelet-derived exosomes is critical to optimizing their therapeutic potential in addiction-related neuropsychiatric disorders. Accordingly, the present study was designed and implemented to evaluate the impact of time-of-day administration in improving the effects of platelet-derived exosomes (pExo) on methamphetamine-induced neurotoxicity. In this study, sixty adult male Wistar rats were divided into five groups and subjected to chronic methamphetamine exposure and subsequent pExo treatment during either the active or the rest phase. Spatial learning and memory were assessed using the Morris water maze, whereas anxiety-like behavior was evaluated through the elevated plus maze and grooming behavior tests. Furthermore, hippocampal indices of cell death, apoptosis, neurogenesis, and neuroinflammation were analyzed. The results demonstrated time-of-day-dependent efficacy of pExo, with administration during the Rest-phase-onset significantly enhancing spatial memory performance (p<0.05), whereas treatment during the active-phase-onset more effectively attenuated anxiety-like behaviors. Moreover, pExo delivery in the Rest-phase-onset led to a greater reduction in apoptosis and a more pronounced induction of neurogenesis relative to the active-phase-onset. However, no significant difference was observed in the expression of Iba1, a marker of neuroinflammation, between the two groups (p=0.35). These findings reveal a time-of-day-dependent modulation of pExo therapy efficacy, suggesting that aligning treatment administration with the rest-activity cycle could optimize neurorestorative outcomes. This time-tailored therapeutic approach may open new avenues for enhancing neural recovery and reducing relapse risk in individuals with substance use disorders.

The consumption of human milk oligosaccharides (HMOs), a key component of breast milk, during early life has been shown to have long-lasting impacts on metabolic processes, immune system function, and nervous system development. The long-term effects of early-life HMO supplementation on behaviours that are associated with metabolic processes, such as food preferences and food choices, and mental health conditions, such as anxiety and depression, are less clear. The present study examined the effects of post-weaning supplementation with two common HMOs, 2'-fucosyllactose (2'FL) and 3'sialyllactose (3'SL), on anxiety-like behavior, sucrose consumption, food preference, and glutamate receptor gene expression in adulthood in Sprague-Dawley rats. We also assessed whether HMO supplementation could attenuate any changes in glutamate receptor gene expression or behavior associated with a high-fat/sucrose (HFS) diet. The present study demonstrated that the effects of HMO supplementation are both sex and dose-dependent, with changes in glutamate receptor gene expression in the nucleus accumbens (NAc) representing the most prominent changes. Effects on sucrose intake were modest and sex-specific, with H/HFS females consuming less sucrose than H/AIN females on the first, but not second, day of testing. This effect was most evident in females that received the high-HMO diet before the HFS challenge and was accompanied by lower GluR1 and GluR2 gene expression in the NAc. Rats fed a HFS diet displayed a preference for palatable food, regardless of early HMO exposure, which may be the result of changes to incentive salience or "wanting" for palatable foods. The findings of this study show a potential link between early-life HMO supplementation, behaviour, and the expression of genes related to synaptic plasticity.