Despite the growing interest in cell- and exosome-based therapies for neurological diseases including Alzheimer's disease (AD), there is still a gap in the investigation of more effective treatments i Show more
Despite the growing interest in cell- and exosome-based therapies for neurological diseases including Alzheimer's disease (AD), there is still a gap in the investigation of more effective treatments in terms of efficacy, safety, and durability of effect. This study aimed to compare the therapeutic potential of astrocyte cells and their derived exosomes (AS-Exos) in restoring cognitive function in a mouse model of AD. AD model was induced by bilateral electrical lesioning of the nucleus basalis of Meynert (NBM). Astrocytes were isolated from neonatal rat brains, and AS-Exos were harvested from astrocyte-conditioned media using an AnaCell extraction kit. Seven days after lesion induction, astrocytes and AS-Exos were stereotaxically injected into the NBM. Four weeks later, behavioral assessments (passive avoidance and locomotor activity), electrophysiological recordings (EEG), and biochemical measurements of hippocampal brain-derived neurotrophic factor (BDNF) and acetylcholine (ACh) levels were performed. AS-Exos were confirmed as cup-shaped vesicles (30-150 nm) expressing the exosomal surface markers CD9, CD63, and CD81. NBM lesions significantly reduced step-through latency (STL), hippocampal BDNF and ACh levels, and disrupted EEG oscillatory patterns. Treatment with AS-Exos markedly improved STL and produced greater increases in hippocampal BDNF and ACh levels compared with AD and AD+saline groups. EEG analysis also revealed enhanced beta, alpha, and gamma power, with the most robust normalization observed in the AS-Exos group. AS-Exos demonstrated superior biochemical and electrophysiological benefits compared with astrocyte transplantation and provided equal or greater improvement in behavioral outcomes. These findings highlight AS-Exos as a promising cell-free therapeutic strategy for alleviating cognitive deficits associated with AD. Show less
The transport of pharmaceutical compounds into aquatic ecosystems poses a significant environmental threat, particularly due to the presence of drugs that cannot be completely removed during wastewate Show more
The transport of pharmaceutical compounds into aquatic ecosystems poses a significant environmental threat, particularly due to the presence of drugs that cannot be completely removed during wastewater treatment processes. Diclofenac (DCF), one of the most widely used nonsteroidal anti-inflammatory drugs worldwide, is among the pharmaceuticals frequently detected in aquatic environments due to its high consumption levels and persistence in the environment. It is known that this compound causes neurotoxicity, behavioral disorders, and physiological stress responses in aquatic organisms even at low concentrations. This study aimed to determine the effects of diclofenac exposure on oxidative stress, circadian rhythm, and behavioral parameters in zebrafish larvae. For this purpose, zebrafish embryos and early-stage larvae were exposed to DCF at concentrations of 0.5, 2.5, and 12.5 μg/L for 120 h. Subsequently, to investigate the effect of DCF on oxidative stress, SOD, CAT, GPX, and AChE enzyme activities and gene expression levels were analyzed. To examine its effects on behavior and circadian rhythm, thigmotaxis and locomotor activity analyses were performed. Additionally, to determine the molecular-level effects of behavioral changes, the expression levels of the bdnf, 5ht4, crhr, bmal1, per, and gnat2 genes were analyzed. Overall, our findings indicate that DCF affects behavioral activity, neurotransmitter metabolism, oxidative stress response, circadian rhythm, and retina-related molecular regulators in zebrafish larvae in a multilevel manner. These results highlight the potential risks of pharmaceutical contaminants on neurodevelopmental processes in aquatic ecosystems and demonstrate that even environmental doses can produce complex responses in biological systems. Show less
Exercise is a potent modulator of mental health, with accumulating evidence highlighting its ability to produce structural and functional changes in the brain. This review synthesizes findings across Show more
Exercise is a potent modulator of mental health, with accumulating evidence highlighting its ability to produce structural and functional changes in the brain. This review synthesizes findings across neurobiological, molecular, and systemic domains to explain how exercise improves outcomes in mood, anxiety, and stress-related disorders. We examine how exercise stimulates brain-derived neurotrophic factor (BDNF), regulates monoaminergic systems (serotonin, dopamine, norepinephrine), modulates inflammatory and oxidative stress pathways, and promotes neurogenesis and synaptic plasticity. The review also explores systemic mechanisms including the gut-brain axis, myokine signaling (e.g., irisin, cathepsin B), and the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, we discuss how exercise influences key psychological mechanisms, including emotion regulation, self-efficacy, and cognitive reappraisal, offering a translational bridge between physiology and psychotherapy. Understanding these overlapping mechanisms can guide clinicians in prescribing exercise as an evidence-based adjunct or standalone therapy for mental health disorders. This model of exercise as medicine has the potential to enhance both accessibility and efficacy of mental health care. Implications for clinical integration, mechanistic research, and policy development are discussed. Show less