The recent investigation was to ascertain whether europinidin could defend rats against scopolamine- tempted deficits in learning and memory. Wistar rats were arbitrarily separated into four clusters and treated as follows: Cluster 1 (normal control) and Cluster 2 (scopolamine-SCOP) received oral administration of 3 ml/kg of 0.5% sodium CMC (vehicle). Clusters 3 and 4 received europinidin (p.o. lower dose-10 and higher-20 mg/kg, respectively) for a 14-day period. The ability to move spontaneously, recall information, and learn were assessed in rats for 15-day, animals were placed for euthanasia, and analyzed for acetylcholine esterase (AChE), choline acetyltransferase (ChAT), antioxidant (CAT, SOD, GSH, and MDA), nitrites, anti-inflammatory (TNF-α, IL-1β, IL-6, and IL-10) and brain-derived neurotrophic factor (BDNF). SCOP caused the animals to lose their memory. SCOP altered the activities of AChE and ChAT, decreased GSH, SOD, and CAT quantity attenuated the levels of IL-10, BDNF, and improved levels of MDA, nitrate, IL-1β, IL-6, and TNF-α in brain tissue. Europinidin effectively reduced the neurobehavioral deficits, oxidative stress, and neuroinflammatory markers affected by SCOP in the treated rats as well as reverted the AChE, ChAT, and BDNF levels back to normal, europinidin lessens the reminiscence impairment affected by scopolamine in rats.

Diets that promote excessive caloric intake, particularly those high in fat and/or sugar, can cause harmful changes in the human body, including the brain. Excess consumption of fat and sugar may impair neuronal function and have both short- and long-term adverse effects. This systematic review examined the influence of high-fat and/or high-sugar dietary patterns on biochemical, molecular, and behavioral changes (PROSPERO protocol number: CRD42024526471). A systematic search was conducted in PubMed, EMBASE, and Scopus, and twenty-eight articles were included for data extraction. The studies indicate that obesogenic and energy-dense dietary patterns induce physiological changes in both the peripheral and central nervous systems, leading to neuronal, functional, and structural adaptations accompanied by biochemical, molecular, and behavioral changes. These adaptations appear to be associated with coordinated changes in gut microbiota composition, glucose and insulin metabolism, and bile acid signaling pathways. These findings support further investigation into strategies for the prevention and treatment of diet-related cognitive impairment. However, additional non-clinical and clinical studies are needed to better elucidate the mechanisms linking energy-dense dietary patterns and excessive caloric intake to these neural changes. An adequate intake of macro- and micronutrients is essential for efficient neuronal function, synaptic activity, and the synthesis of neurotransmitters and protein components [ 4 , 5 ]. A growing body of neuroscientific evidence shows that adult mammal brains can undergo structural and functional remodeling in response to learning or experience [ 6 , 7 ]. This process enables adaptive plasticity in mammalian brains, supporting learning, memory formation, and recovery of neural circuitry after injury, as demonstrated in experimental animal models [ 8 ]. Body weight did not differ among groups; however, sucrose-derived energy intake was higher in both HS group compared to CD [ 24 ] High-sugar diet (HS): 1.5 g/100 g from fat (sunflower oil), 20.4 g/100 g from carbohydrates (fructose), and 9.2 g/100 g from proteins (casein) Standard control diet (CD): 1.5 g/100 g from fat (sunflower oil), 20.4 g/100 g from carbohydrates (cornstarch), and 9.2 g/100 g from proteins (casein) Male Wistar rats Age = ~ 3 weeks-old N = ~ 32 Animals were allocated into three groups and fed either CD for 42 days, HS for 21 days, or HS for 21 days followed by CD for an additional 21 days Several of the alterations in the frontal córtex (BDNF, CML, CEL, acetylcholinesterase activity, dysregulation of neurotransmitter levels) persisted after switching to the control diet, thus pointing to adolescence as a critical phase. The behavioral changes induced by a high-calorie diet, as reported in the systematically selected studies, are presented in Table 2 . While a few studies found no changes in locomotor activity and memory, most studies indicated that a high-calorie diet can cause various cognitive and other changes. Almost all studies described anxiety- and depression-like behaviors in both young and adult, male and female animals following acute or chronic exposure to high-calorie diets. Other effects included decreased exploratory behavior, social interaction and social motivation and recognition; decreased learning and memory and decreased cognitive flexibility; increased passive stress coping; cognitive impairment, and trace fear conditioning. In addition, the offspring of mothers exposed to a high-fat and/or high-sugar diet exhibited anxious and/or depression-like behaviors. The mothers also showed increased passive stress coping, spent more time away from the nest, and were less likely to nest-build. Table 2 Behavioral changes induced by a high-calorie diet, as reported in the systematically selected studies Diet Type of Alteration Alteration Reference HFD Behavioral ↓ exploratory behavior in female offspring ↑ active coping strategy in female and male offspring [ 20 ] HFD Behavioral and Social Dams ↑ time spent away from the nest ↓ the frequency of nest building ↑ passive stress coping F1 offspring ↑ anxiety- and depressive-like behaviors ↑ passive stress coping ↓ social interaction [ 21 ] HFD Behavioral and Cognitive ↓ learning and memory in F1, The hippocampus was the most frequently examined structure in the studies included in this systematic review. Changes described include increases and decreases in the expression of various molecules such as BDNF and inflammatory markers, including TNF-α, IL-1β, and IL-6. Changes were also described in the hypothalamus, prefrontal cortex, substantia nigra , striatum, and microglia. Some authors did not isolate specific structures for dosages but also showed changes in the general structure of the brain, and others provided results on plasma changes, such as changes in corticosterone levels. The detrimental effects of consuming foods high in saturated fat, sodium, sugar, and easily assimilated carbohydrates appear to be due not only to their very low nutritional value but also to their tendency to promote non-homeostatic behaviors characterized by repetitive and excessive consumption of foods, which can alter gut-brain communication and the links between taste perception and nutrient response [ 51 , 52 ]. Ultimately, it can lead to a reduction in specific biomarkers such as BDNF [ 14 , 63 , 64 ] and result in acute and long-term changes associated with significant alterations in brain reward circuitry, contributing to the development of anxiety and depression-like behaviors in animal models [ 65 , 66 ]. Metabolic abnormalities such as decreased expression of glucose transporters and alterations in insulin metabolism can also cause neuronal changes at the morphological and physiological level, reflected in a reduction in short- and long-term potentiation response and a decrease in specific markers of synaptic neuronal plasticity [ 59 , 67 ].

One hypothesis to account for the onset and severity of neurological disorders is the loss of trophic support. Indeed, changes in the levels and activities of brain-derived neurotrophic factor (BDNF) occur in numerous neurodegenerative and neuropsychiatric diseases. A deficit promotes vulnerability whereas a gain of function facilitates recovery by enhancing survival, synapse formation and synaptic plasticity. Implementation of 'BDNF therapies', however, faces numerous methodological and pharmacokinetic issues. Identifying BDNF mimetics that activate the BDNF receptor or downstream targets of BDNF signaling represent an alternative approach. One mechanism that shows great promise is to study the interplay of BDNF and glucocorticoid hormones, a major class of natural steroid secreted during stress reactions and in synchrony with circadian rhythms. While small amounts of glucocorticoids support normal brain function, excess stimulation by these steroid hormones precipitates stress-related affective disorders. To date, however, because of the paucity of knowledge of underlying cellular mechanisms, deleterious effects of glucocorticoids are not prevented following extreme stress. In the present review, we will discuss the complementary roles shared by BDNF and glucocorticoids in synaptic plasticity, and delineate possible signaling mechanisms mediating these effects.

Brain-derived neurotrophic factor (BDNF) is one of the most studied neurotrophins in the mammalian brain, essential not only to the development of the central nervous system but also to synaptic plasticity. BDNF is present in various brain areas, but highest levels of expression are seen in the cerebellum and hippocampus. After birth, BDNF acts in the cerebellum as a mitogenic and chemotactic factor, stimulating the cerebellar granule cell precursors to proliferate, migrate and maturate, while in the hippocampus BDNF plays a fundamental role in synaptic transmission and plasticity, representing a key regulator for the long-term potentiation, learning and memory. Furthermore, the expression of BDNF is highly regulated and changes of its expression are associated with both physiological and pathological conditions. The purpose of this review is to provide an overview of the current state of knowledge on the BDNF biology and its neurotrophic role in the proper development and functioning of neurons and synapses in two important brain areas of postnatal neurogenesis, the cerebellum and hippocampus. Dysregulation of BDNF expression and signaling, resulting in alterations in neuronal maturation and plasticity in both systems, is a common hallmark of several neurodevelopmental diseases, such as autism spectrum disorder, suggesting that neuronal malfunction present in these disorders is the result of excessive or reduced of BDNF support. We believe that the more the relevance of the pathophysiological actions of BDNF, and its downstream signals, in early postnatal development will be highlighted, the more likely it is that new neuroprotective therapeutic strategies will be identified in the treatment of various neurodevelopmental disorders.

psychological stress decreases BDNF expression, which has detrimental effects on hippocampal volume and can lead to depression. As a physical stressor, aerobic The neurobiological effects of physical exercise involve possible interrelated effects on brain structure, brain function, and cognition. Research in humans has demonstrated that consistent aerobic exercise (e.g., 30 minutes every day) may induce improvements in certain cognitive functions, neuroplasticity and behavioral plasticity; some of these long-term effects may include increased neuron gro The "stress hormone", cortisol, is a glucocorticoid that binds to glucocorticoid receptors. Psychological stress induces the release of cortisol from the adrenal gland by activating the hypothalamic–pituitary–adrenal axis (HPA axis). Short-term increases in cortisol levels are associated with adaptive cognitive improvements, such as enhanced inhibitory control; however, excessively high exposure or prolonged exposure to high levels of cortisol causes impairments in cognitive control and has neurotoxic effects in the human brain. For example, chronic psychological stress decreases BDNF expression, which has detrimental effects on hippocampal volume and can lead to depression. As a physical stressor, aerobic exercise stimulates cortisol secretion in an intensity-dependent manner; however, it does not result in long-term increases in cortisol production since this exercise-induced effect on cortisol is a response to transient negative energy balance. Aerobic exercise increases physical fitness and lowers neuroendocrine (i.e., HPA axis) reactivity and therefore reduces the biological response to psychological stress in humans (e.g., reduced cortisol release and attenuated heart rate response). Exercise also reverses stress-induced decreases in BDNF expression and signaling in the brain, thereby acting as a buffer against stress-related diseases like depression. Glutamate, one of the most common…

Icariin, a major bioactive flavonoid extracted from Epimedium species, has demonstrated promising neuroprotective and antidepressant-like effects in preclinical research. However, the magnitude and consistency of these effects remain unclear due to substantial methodological heterogeneity across studies. Therefore, we conducted a systematic review and meta-analysis to evaluate the antidepressant efficacy of icariin in rodent models of depression. Literature searches were performed in Scopus, PubMed and Embase up to May 2025, following PRISMA 2020 guidelines. Twenty-three studies were included in the qualitative synthesis, and thirteen provided sufficient data for quantitative analysis. icariin administration significantly improved anhedonia-like behavior in the sucrose preference test (SPT), with a pooled Hedges’ g of 2.26 (95% CI: 1.56–2.96), and markedly reduced immobility in the forced swim test (FST), with a pooled Hedges’ g of 3.64 (95% CI: 2.65–4.64), indicating strong and robust antidepressant-like effects. Both findings were comparable in magnitude to conventional antidepressants. Meta-regression revealed that longer duration of depression model induction was associated with stronger behavioral improvement, whereas dose did not significantly predict efficacy. Mechanistic evidence suggests that icariin acts through multi-target neuroprotective pathways, including enhancement of BDNF-mediated neuroplasticity, inhibition of neuroinflammation, and regulation of HPA-axis dysfunction. Although methodological variability, male-biased animal selection, and pharmacokinetic limitations were identified, the overall evidence supports icariin as a promising antidepressant candidate for further translational investigation.

<h4>Background</h4>Alzheimer disease (AD) is the most common cause of dementia in the world with the prevalence expected to increase threefold to 152.8 million people by 2050. The current medications provide a short-term ameliorative effect, and this requires development of disease-modifying treatments, which address the biological pathogenesis.<h4>Methods</h4>This review assesses the changing neuropharmacological environment offering a critical analysis of anti-amyloid monoclonal antibodies and investigates the so-called expanding frontier of non-amyloid targets. It also examines the approaches of clinical trials and the trend of biomarker-based patient selection and precision medicine.<h4>Results</h4>Although β-site APP-cleaving enzyme 1 (BACE1) and secretase inhibitors did not achieve success in clinical trials because of mechanism-based toxicity and cognitive impairment, new monoclonal antibodies such as lecanemab and donanemab have shown high amyloid plaque clearance and reduced cognitive deterioration. Nevertheless, the treatments are associated with amyloid-related imaging abnormalities (ARIA). In addition to amyloid, studies are focusing on tau hyperphosphorylation, neuroinflammation through triggering receptor on myeloid cells 2 (TREM2) and NLR family pyrin domain containing 3 (NLRP3) and growth factor-mediated synaptic plasticity through brain-derived neurotrophic factor (BDNF).<h4>Conclusions</h4>AD treatment has entered the new era that demands a paradigm shift from monotherapies to multi-target cocktails. The future lies in precision neuropharmacology, where genetic stratification and individual biomarker analysis are used to provide the correct treatment at the most appropriate biological stage.

<h4>Background</h4>The complex pathophysiology of ischemic stroke (IS) involves initial injury followed by secondary cascades and endogenous repair. This review systematically explores how electroacupuncture (EA) precisely modulates these processes.<h4>Methods</h4>We systematically searched and summarized all papers related to EA treatment for stroke using the China National Knowledge Infrastructure (CNKI) and PubMed databases.<h4>Results</h4>We detail EA's key mechanisms in reducing initial and secondary damage, including the suppression of inflammatory responses (e.g., NF-κB, inflammasomes, gut-brain axis), mitigation of oxidative stress (Nrf2/HO-1), attenuation of excitotoxicity (NMDAR, GLT-1), and inhibition of diverse forms of regulated cell death (apoptosis, pyroptosis, ferroptosis). Critically, EA also actively promotes vital repair mechanisms by enhancing cerebral blood flow, protecting blood-brain barrier integrity, promoting angiogenesis (VEGF, HIF, Notch, Wnt pathways), and fostering extensive neural regeneration and plasticity (neurogenesis, neurotrophic factors, myelination, synaptic changes, network reorganization) at molecular, cellular, and network levels. These well-documented mechanistic actions provide a strong scientific basis for the observed clinical benefits of EA in improving major poststroke sequelae, encompassing motor, cognitive, language, and emotional deficits.<h4>Conclusions</h4>The review highlights the potential for enhanced outcomes through combined therapy approaches and identifies future research avenues leveraging advanced technologies like multi-omics and AI for personalized precision EA. EA stands as a scientifically grounded, multi-target therapy improving stroke recovery.

<h4>Aims</h4>This study aimed to address the lack of comprehensive reviews on the comorbidity between depression and type 2 diabetes mellitus (T2DM) by investigating their complex connections and identifying emerging research trends.<h4>Methods</h4>We conducted an in-depth review combining macro bibliometric analysis and micro content interpretation of literature. Based on the bibliometric analysis of 3,986 papers in Web of Science Core Collection and 238 clinical trials in PubMed published between 2016 and 2025, the institutions, countries, authors and keywords were investigated, and the research maps were drawn by bibliometric software such as VOSviewer, Citespace and Bibliometrix. Meanwhile, micro interpretation entails in-depth content analysis of key articles to develop personal insights.<h4>Results</h4>The analysis identified 3,986 relevant papers and 238 clinical trials, revealing a consistent overall growth in research volume. Key contributing entities and potential future research hotspots are mapped, such as the link between comorbidity and Parkinson's disease and obesity. Also, our micro-interpretation identified the comorbidity mechanism through hypothalamic pituitary adrenal axis (HPA axis) and Brain derived neurotrophic factor (BDNF) and integrated treatment strategy of depression and T2DM.<h4>Conclusion</h4>The results of the study outlined the evolving knowledge and research focus in this field. This study provides a comprehensive review of the comorbidity of depression and T2DM, emphasizing the mechanism and treatment of the comorbidity. The current research focus is on the HPA axis and BDNF, and the integrated treatment idea to solve depression and T2DM at the same time has the potential to change in chronic disease management and clinical practice.