Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression.

RATIONALE: Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed light on the distinctive features of its antidepressant effects. OBJECTIVES: We set out to assess the behavioral impact of acute and prolonged PSI administration on WKY and WIS rats, employing Novel Object Recognition (NORT), Social Interaction (SI), and Forced Swimming Test (FST). Our secondary objectives involved exploring strain-specific alterations in neuroplasticity-related parameters, including brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated protein (Arc). METHODS: Conducting post-acute and extended assessments after a single PSI administration, we applied behavioral tests and biochemical analyses to measure serum BDNF levels and neuroplasticity-related parameters in the prefrontal cortex. Statistical analyses were deployed to discern significant differences between the rat strains and assess the impact of PSI on behavioral and biochemical outcomes. RESULTS: Our findings uncovered significant behavioral disparities between WKY and WIS rats, indicating passive behavior and social withdrawal in the former. PSI demonstrated pronounced pro-social and antidepressant effects in both strains, each with its distinctive temporal trajectory. Notably, we identified strain-specific variations in BDNF-related signaling and observed the modulation of Arc expression in WKY rats. CONCLUSIONS: Our study delineated mood-related behavioral nuances between WKY and WIS rat strains, underscoring the antidepressant and pro-social properties of PSI in both groups. The distinct temporal patterns of observed changes and the identified strain-specific neuroplasticity alterations provide valuable insights into the TRD phenotype and the mechanisms underpinning the efficacy of PSI.

The Neuroprotective Effects of Oroxylum indicum Extract in SHSY-5Y Neuronal Cells by Upregulating BDNF Gene Expression under LPS Induced Inflammation.

The brain-derived neurotrophic factor (BDNF) plays a crucial role during neuronal development as well as during differentiation and synaptogenesis. They are important proteins present in the brain that support neuronal health and protect the neurons from detrimental signals. The results from the present study suggest BDNF expression can be increase up to ~8-fold by treating the neuroblastoma cells SHSY-5Y with an herbal extract of Oroxylum indicum (50 µg/mL) and ~5.5-fold under lipopolysaccharides (LPS)-induced inflammation conditions. The Oroxylum indicum extract (Sabroxy) was standardized to 10% oroxylin A, 6% chrysin, and 15% baicalein. In addition, Sabroxy has shown to possess antioxidant activity that could decrease the damage caused by the exacerbation of radicals during neurodegeneration. A mode of action of over expression of BDNF with and without inflammation is proposed for the Oroxylum indicum extract, where the three major hydroxyflavones exert their effects through additive or synergistic effects via five possible targets including GABA, Adenoside A2A and estrogen receptor bindings, anti-inflammatory effects, and reduced mitochondrial ROS production.

Up-regulation of systemic and local BDNF in non-allergic Nasal Polyps in China.

Objective: Although the role of brain-derived neurotrophic factor (BDNF) in allergic rhinitis and/or nasal polyps (NPs) development has been studied, the contribution of BDNF in non-allergic NPs has not been evaluated yet. This study was to investigate the possible role of BDNF in non-allergic NPs pathogenesis. Methods: The study was carried out at The Second Hospital of Shandong University from December 2020 to November 2021. The non-allergic NPs patients (n=26) and the control group (n=22) were included. Lund-Mackay CT scores, nasal endoscopy scores, and pulmonary function testing were evaluated before surgery. Tissue and serum levels of BDNF, eosinophil cationic protein (ECP), and cytokeratins 5 (CK5) were assessed between different groups. Result: The BDNF level in serum and tissue, CK5 count, and eosinophil infiltration in tissue were higher in non-allergic NPs. The eosinophils infiltration, ECP mRNA expression level, as well as BDNF mRNA level were increased in the BDNFhigh subgroup compared with BDNFlow subgroup. Significantly negative correlations between BDNF count and the situation of airway obstruction were found in non-allergic NPs. Conclusion: BDNF may have both local and systemic effects in non-allergic NPs pathogenesis. BDNF may be a possible therapeutic target or an indicator for eosinophilic NPs management.

[Tongdu Tiaoshen acupuncture for subjective tinnitus:a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of Tongdu Tiaoshen acupuncture (acupuncture for promoting the circulation of the governor vessel and regulating the spirit) for subjective tinnitus, and explore its potential mechanism. METHODS: A total of 92 patients with subjective tinnitus were randomly divided into an acupuncture group (46 cases, 5 cases dropped out) and a medication group (46 cases, 2 cases dropped out). The acupuncture group received Tongdu Tiaoshen acupuncture at Shuigou (GV 26), Yintang (GV 24+), Shenting (GV 24), Baihui (GV 20), Fengfu (GV 16), Dazhui (GV 14) and Zhongzhu (TE 3), Tinghui (GB 2), Yifeng (TE 17) on the affected side, 30 min each time, once every other day, 3 times a week. The medication group was orally administered ginkgo biloba leaves tablets (40 mg each time) and mecobalamin tablets (0.5 mg each time), 3 times a day. Both groups were treated for 4 weeks. The scores of tinnitus severity, tinnitus loudness visual analogue scale (VAS) and depression anxiety stress scale-21(DASS-21) before and after treatment were observed in the two groups, serum level of brain-derived neurotrophic factor (BDNF) before and after treatment in the two groups was detected, and the clinical effect was evaluated in the two groups. RESULTS: After treatment，the scores of tinnitus severity, tinnitus loudness VAS and DASS-21 were decreased compared with those before treatment in the two groups (P<0.01), and the scores in the acupuncture group were lower than those in the medication group (P<0.05). After treatment, the serum level of BDNF was decreased compared with that before treatment in the two groups (P<0.01), and the serum level of BDNF in the acupuncture group was lower than that in the medication group (P<0.05). The total effective rate of the acupuncture group was 82.9% (34/41), which was higher than 70.5% (31/44) in the medication group (P<0.05). CONCLUSION: Tongdu Tiaoshen acupuncture could improve the severity of tinnitus, tinnitus loudness and negative emotion in patients with subjective tinnitus. Its mechanism may be related to the regulation of serum level of BDNF and thus affect auditory central plasticity.

[Brain-derived neurotrophic factor in the acute and early recovery period of ischemic stroke: the role of nocturnal hypoxemia]. / Mozgovoi neirotroficheskii faktor pri ishemicheskom insul'te v ostrom i rannem vosstanovitel'nom periodakh: rol' nochnoi gipoksemii.

OBJECTIVE: To study the relationship between brain-derived neurotrophic factor (BDNF) and the severity of nocturnal hypoxemia in patients in the acute and early recovery period of ischemic stroke (IS). MATERIAL AND METHODS: We enrolled 44 patients (27 men, 17 women), aged 18-85 years, in the acute phase of IS. At 3-month follow-up, 35 people were examined (21 men and 14 women). In the acute period, in addition to routine diagnostic procedures, respiratory monitoring was carried out, and the serum level of BDNF was measured by enzyme-linked immunosorbent assay. BDNF level was also evaluated at 3-month follow-up visit. Neurological status and its dynamics in the acute period of stroke were assessed as part of the clinical routine according to the National Institutes of Health Stroke Scale (NIHSS) at admission and discharge. RESULTS: We found a direct correlation between the duration of hypoxemia with SpO2 less than 90% (r=0.327, p=0.035) and less than 85% (r=0.461, p=0.003) and BDNF level in the acute phase of IS. BDNF level in the acute period of IS was negatively correlated with the minimum saturation value (r=-0.328, p=0.034). There was a direct relationship between BDNF level in the early recovery period and the duration of hypoxemia with SpO2 less than 85% (r=-0.389, p=0.028). A regression model showed that BDNF level was associated with the minimum SpO2 level. No significant associations were found with indicators of sleep-disordered breathing severity, such as the apnea-hypopnea index and the oxygen desaturation index. CONCLUSION: The severity of nocturnal hypoxemia is associated with the increase in BDNF levels both in the acute and recovery periods of IS, regardless of the presence of concomitant breathing disorders during sleep.

Features of Remyelination after Transplantation of Olfactory Ensheathing Cells with Neurotrophic Factors into Spinal Cord Cysts.

This paper shows for the first time that co-transplantation of human olfactory ensheathing cells with neurotrophin-3 into spinal cord cysts is more effective for activation of remyelination than transplantation of cells with brain-derived neurotrophic factor and a combination of these two factors. The studied neurotrophic factors do not affect proliferation and migration of ensheathing cells in vitro. It can be concluded that the maximum improvement of motor function in rats receiving ensheathing cells with neurotrophin-3 is largely determined by activation of remyelination.

The effect of olanzapine on spatial memory impairment, depressive-like behavior, pain perception, and BDNF and synaptophysin expression following childhood chronic unpredictable mild stress in adult male and female rats.

Chronic unpredictable mild stress (CUMS) method has been introduced as a rodent model of depression. On the other hand, olanzapine, as an antipsychotic, can induce antidepressant and antipsychotic effects. Also, olanzapine may improve cognitive functions. Both CUMS and olanzapine can also affect the expression level of brain-derived neurotrophic factor (BDNF) and synaptophysin, the molecular factors involved in synaptic function, and learning and memory. In this study, we investigated the effect of olanzapine on locomotor activity (using open field test), pain threshold (using hot plate), depressive-like behavior (using forced swim test), spatial learning and memory (using Morris water maze), and BDNF and synaptophysin hippocampal expression (using real-time PCR) in both male and female CUMS rats. CUMS was performed for three consecutive weeks. Olanzapine was also injected intraperitoneally at the dose of 5 mg/kg. Our data showed that olanzapine can reverse the effects of CUMS on behavioral functions and BDNF and synaptophysin expression levels in the hippocampus of both males and females. It was also shown that olanzapine effects on spatial memory, pain perception, and BDNF and synaptophysin level were stronger in females than males. In conclusion, we suggested that the therapeutic effects of olanzapine in CUMS rats may be closely related to the function of BDNF and synaptophysin. Also, the therapeutic effects of olanzapine may be stronger in females. Therefore, and for the first time, we showed that there may be a sex difference in the effects of olanzapine on behavioral and molecular changes following CUMS.

Potentiation of antidepressant effects: NPY1R agonist and ketamine synergy enhances TrkB signaling and neurogenesis in the ventral hippocampus.

BACKGROUND: Major Depressive Disorder (MDD) poses a significant challenge to global health, with current treatments often limited by efficacy and onset delays. This study explores the synergistic antidepressant-like effects of an NPY1R agonist and Ketamine, targeting their neurobiological interactions within the ventral hippocampus. RESEARCH DESIGN AND METHODS: Utilizing a preclinical model, this study administered Neuropeptide Y receptor 1 (NPY1R) agonist and Ketamine, both separately and in combination, through intracerebroventricular (icv) and intranasal (i.n.) routes. The Forced Swimming Test (FST) was employed to assess antidepressant-like activity, while in situ Proximity Ligation Assay and immunohistochemistry were used to examine NPY1R/TrkB heteroreceptor complexes and BDNF expression in the ventral dentate gyrus (DG), along with neurogenesis markers. RESULTS: The combined treatment significantly reduced immobility in the FST, indicative of enhanced antidepressant-like effects, correlated with increased formation of NPY1R/TrkB complex and brain-derived neurotrophic factor (BDNF) expression in the ventral DG. These molecular alterations were associated with increased neurogenesis. CONCLUSIONS: The coadministration of an NPY1R agonist and Ketamine in a rodent model demonstrated potentiated antidepressant responses through synergistic neurobiological pathways, including TrkB signaling and hippocampal neurogenesis. This indicates a novel therapeutic strategy for MDD, warranting further clinical investigation to fully understand its implications.

Interaction effect of crocin and citalopram on memory and locomotor activity in rats: an insight into BDNF and synaptophysin levels in the hippocampus.

Selective serotonin reuptake inhibitors (SSRIs) are widely used drugs for the treatment of depression. Citalopram is one of the most prescribed SSRIs that is useful for the treatment of depression, obsessive-compulsive disorder, and anxiety disorders. On the other hand, crocin (active constitute of saffron) has pro-cognitive and mood enhancer effects. Also, both citalopram and crocin affect the function and expression of brain-derived neurotrophic factor (BDNF) and synaptophysin, two molecular factors that are involved in cognitive functions and mood. In the present study, we aim to investigate the interaction effect of citalopram and crocin on rats' performance in the open field test (locomotor activity and anxiety-like behavior) and the shuttle box (passive avoidance memory). Citalopram was injected at the doses of 10, 30, and 50 mg/kg, and crocin was injected at the dose of 50 mg/kg; all administrations were intraperitoneal. Real-time PCR was used to assess the expression level of BDNF and synaptophysin in the hippocampus. The results showed that citalopram (30 and 50 mg/kg) impaired passive avoidance memory and decreased BDNF and synaptophysin expression in the hippocampus, while crocin reversed memory impairment, and BDNF and synaptophysin expression in the hippocampus of rats received citalopram 30 mg/kg. Also, crocin partially showed these effects in rats that received citalopram 50 mg/kg. The results of the open field test were unchanged. In conclusion, we suggested that BDNF and synaptophysin may be involved in the effects of both citalopram and crocin.

Enhancing Cognitive Functions and Neuronal Growth through NPY1R Agonist and Ketamine Co-Administration: Evidence for NPY1R-TrkB Heteroreceptor Complexes in Rats.

This study investigates the combined effects of the neuropeptide Y Y1 receptor (NPY1R) agonist [Leu31-Pro34]NPY at a dose of 132 µg and Ketamine at 10 mg/Kg on cognitive functions and neuronal proliferation, against a backdrop where neurodegenerative diseases present an escalating challenge to global health systems. Utilizing male Sprague-Dawley rats in a physiological model, this research employed a single-dose administration of these compounds and assessed their impact 24 h after treatment on object-in-place memory tasks, alongside cellular proliferation within the dorsal hippocampus dentate gyrus. Methods such as the in situ proximity ligation assay and immunohistochemistry for proliferating a cell nuclear antigen (PCNA) and doublecortin (DCX) were utilized. The results demonstrated that co-administration significantly enhanced memory consolidation and increased neuronal proliferation, specifically neuroblasts, without affecting quiescent neural progenitors and astrocytes. These effects were mediated by the potential formation of NPY1R-TrkB heteroreceptor complexes, as suggested by receptor co-localization studies, although further investigation is required to conclusively prove this interaction. The findings also highlighted the pivotal role of brain-derived neurotrophic factor (BDNF) in mediating these effects. In conclusion, this study presents a promising avenue for enhancing cognitive functions and neuronal proliferation through the synergistic action of the NPY1R agonist and Ketamine, potentially via NPY1R-TrkB heteroreceptor complex formation, offering new insights into therapeutic strategies for neurodegenerative diseases.

Comparing the effect of fluoxetine, escitalopram, and sertraline, on the level of BDNF and depression in preclinical and clinical studies: a systematic review.

Brain-derived neurotrophic factor (BDNF) dysfunction is one of the most important mechanisms underlying depression. It seems that selective serotonin reuptake inhibitors (SSRIs) improve depression via affecting BDNF level. In this systematic review, for the first time, we aimed to review the effect of three SSRIs including fluoxetine, escitalopram, and sertraline, on both depression and BDNF level in preclinical and clinical studies. PubMed electronic database was searched, and 193 articles were included in this study. After reviewing all manuscripts, only one important difference was found: subjects. We found that SSRIs induce different effects in animals vs. humans. Preclinical studies showed many controversial effects, while human studies showed only two effects: improvement of depression, with or without the improvement of BDNF. However, most studies used chronic SSRIs treatment, while acute SSRIs were not effectively used and evaluated. In conclusion, it seems that SSRIs are reliable antidepressants, and the improvement effect of SSRIs on depression is not dependent to BDNF level (at least in human studies).

Brain-derived neuerotrophic factor and related mechanisms that mediate and influence progesterone-induced neuroprotection.

Historically, progesterone has been studied significantly within the context of reproductive biology. However, there is now an abundance of evidence for its role in regions of the central nervous system (CNS) associated with such non-reproductive functions that include cognition and affect. Here, we describe mechanisms of progesterone action that support its brain-protective effects, and focus particularly on the role of neurotrophins (such as brain-derived neurotrophic factor, BDNF), the receptors that are critical for their regulation, and the role of certain microRNA in influencing the brain-protective effects of progesterone. In addition, we describe evidence to support the particular importance of glia in mediating the neuroprotective effects of progesterone. Through this review of these mechanisms and our own prior published work, we offer insight into why the effects of a progestin on brain protection may be dependent on the type of progestin (e.g., progesterone versus the synthetic, medroxyprogesterone acetate) used, and age, and as such, we offer insight into the future clinical implication of progesterone treatment for such disorders that include Alzheimer's disease, stroke, and traumatic brain injury.

Periodontal tissue regeneration with cementogenesis after application of brain-derived neurotrophic factor in 3-wall inflamed intra-bony defect.

OBJECTIVE: The purpose of this study is to investigate regenerative process by immunohistochemical analysis and evaluate periodontal tissue regeneration following a topical application of BDNF to inflamed 3-wall intra-bony defects. BACKGROUND: Brain-derived neurotrophic factor (BDNF) plays a role in the survival and differentiation of central and peripheral neurons. BDNF can regulate the functions of non-neural cells, osteoblasts, periodontal ligament cells, endothelial cells, as well as neural cells. Our previous study showed that a topical application of BDNF enhances periodontal tissue regeneration in experimental periodontal defects of dog and that BDNF stimulates the expression of bone (cementum)-related proteins and proliferation of human periodontal ligament cells. METHODS: Six weeks after extraction of mandibular first and third premolars, 3-wall intra-bony defects were created in mandibular second and fourth premolars of beagle dogs. Impression material was placed in all of the artificial defects to induce inflammation. Two weeks after the first operation, BDNF (25 and 50 µg/mL) immersed into atelocollagen sponge was applied to the defects. As a control, only atelocollagen sponge immersed in saline was applied. Two and four weeks after the BDNF application, morphometric analysis was performed. Localizations of osteopontin (OPN) and proliferating cell nuclear antigen (PCNA)-positive cells were evaluated by immunohistochemical analysis. RESULTS: Two weeks after application of BDNF, periodontal tissue was partially regenerated. Immunohistochemical analyses revealed that cells on the denuded root surface were positive with OPN and PCNA. PCNA-positive cells were also detected in the soft connective tissue of regenerating periodontal tissue. Four weeks after application of BDNF, the periodontal defects were regenerated with cementum, periodontal ligament, and alveolar bone. Along the root surface, abundant OPN-positive cells were observed. Morphometric analyses revealed that percentage of new cementum length and percentage of new bone area of experimental groups were higher than control group and dose-dependently increased. CONCLUSION: These findings suggest that BDNF could induce cementum regeneration in early regenerative phase by stimulating proliferation of periodontal ligament cells and differentiation into periodontal tissue cells, resulting in enhancement of periodontal tissue regeneration in inflamed 3-wall intra-bony defects.

Intracerebroventricular BDNF infusion may reduce cerebral ischemia/reperfusion injury by promoting autophagy and suppressing apoptosis.

Here, it was aimed to investigate the effects of intracerebroventricular (ICV) Brain Derived Neurotrophic Factor (BDNF) infusion for 7 days following cerebral ischemia (CI) on autophagy in neurons in the penumbra. Focal CI was created by the occlusion of the right middle cerebral artery. A total of 60 rats were used and divided into 4 groups as Control, Sham CI, CI and CI + BDNF. During the 7-day reperfusion period, aCSF (vehicle) was infused to Sham CI and CI groups, and BDNF infusion was administered to the CI + BDNF group via an osmotic minipump. By the end of the 7th day of reperfusion, Beclin-1, LC3, p62 and cleaved caspase-3 protein levels in the penumbra area were evaluated using Western blot and immunofluorescence. BDNF treatment for 7 days reduced the infarct area after CI, induced the autophagic proteins Beclin-1, LC3 and p62 and suppressed the apoptotic protein cleaved caspase-3. Furthermore, rotarod and adhesive removal test times of BDNF treatment started to improve from the 4th day, and the neurological deficit score from the 5th day. ICV BDNF treatment following CI reduced the infarct area by inducing autophagic proteins Beclin-1, LC3 and p62 and inhibiting the apoptotic caspase-3 protein while its beneficial effects were apparent in neurological tests from the 4th day.

tiRNA-Gly-GCC-001 in major depressive disorder: Promising diagnostic and therapeutic biomarker.

BACKGROUND AND PURPOSE: In major depressive disorder (MDD), exploration of biomarkers will be helpful in diagnosing the disorder as well as in choosing a treatment and predicting the treatment response. Currently, tRNA-derived small ribonucleic acids (tsRNAs) have been established as promising non-invasive biomarker candidates that may enable a more reliable diagnosis or monitoring of various diseases. Herein, we aimed to explore tsRNA expression together with functional activities in MDD development. EXPERIMENTAL APPROACH: Serum samples were obtained from patients with MDD and healthy controls, and small RNA sequencing (RNA-Seq) was used to profile tsRNA expression. Dysregulated tsRNAs in MDD were validated by quantitative real-time polymerase chain reaction (qRT-PCR). The diagnostic utility of specific tsRNAs and the expression of these tsRNAs after antidepressant treatment were analysed. KEY RESULTS: In total, 38 tsRNAs were significantly differentially expressed in MDD samples relative to healthy individuals (34 up-regulated and 4 down-regulated). qRT-PCR was used to validate the expression of six tsRNAs that were up-regulated in MDD (tiRNA-1:20-chrM.Ser-GCT, tiRNA-1:33-Gly-GCC-1, tRF-1:22-chrM.Ser-GCT, tRF-1:31-Ala-AGC-4-M6, tRF-1:31-Pro-TGG-2 and tRF-1:32-chrM.Gln-TTG). Interestingly, serum tiRNA-Gly-GCC-001 levels exhibited an area under the ROC curve of 0.844. Moreover, tiRNA-Gly-GCC-001 is predicted to suppress brain-derived neurotrophic factor (BDNF) expression. Furthermore, significant tiRNA-Gly-GCC-001 down-regulation was evident following an 8-week treatment course and served as a promising baseline predictor of patient response to antidepressant therapy. CONCLUSION AND IMPLICATIONS: Our current work reports for the first time that tiRNA-Gly-GCC-001 is a promising MDD biomarker candidate that can predict patient responses to antidepressant therapy.

Fasting, a Potential Intervention in Alzheimer's Disease.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the onset of symptoms, typically occurring later in life, and significant deficits in cognitive functions including learning, memory, speech, and behavior. Ongoing research endeavors seek to explore methods for preventing and treating AD, as well as delving into the molecular mechanisms underlying existing and novel therapeutic approaches encompassing exercise, diet, and drug regimens for individuals with AD or those at risk of developing AD. Among these interventions, dietary interventions have garnered increasing attention due to their potential in addressing the disease. Eating is among the most fundamental of human daily activities, and controlled dietary practices, such as fasting, have gained prominence as essential clinical methods for disease prevention and treatment. Research findings indicate that fasting holds promise in effectively alleviating and improving the cognitive decline associated with age or as consequence of disease. The clinical efficacy of fasting in addressing AD and related disorders might be grounded in its influence on various molecular mechanisms, including neuroinflammation, glial cell activation, insulin resistance, autophagy regulation, nerve regeneration, the gut microbiome, and accumulations of amyloid-ß and tau proteins. The present study reviews possible molecular mechanisms underpinning the therapeutic effects of fasting in patients with AD, as well as in models of the disorder, to establish a theoretical basis for using fasting as a viable approach to treat AD.

Chronic REM sleep deprivation leads to manic- and OCD-related behaviors, and decreases hippocampal BDNF expression in female rats.

BACKGROUND: Rapid-eye movement (REM) sleep deprivation (SD) can induce manic-like behaviors in rodents. On the other hand, lithium, as one of the oldest drugs used in neuropsychiatric disorders, is still one of the best drugs for the treatment and control of bipolar disorder. In this study, we aimed to investigate the role of chronic short-term REM SD in the induction of manic-like behaviors in female rats. METHODS: The rats were exposed to REM SD for 14 days (6 hours/day). Lithium was intraperitoneally injected at the doses of 10, 50, and 100 mg/kg. RESULTS: REM SD induced hyperactivity and OCD-like behavior, and decreased anxiety, depressive-like behavior, and pain subthreshold. REM SD also impaired passive avoidance memory and decreased hippocampal brain-derived neurotrophic factor (BDNF) expression level. Lithium at the doses of 50 and 100 mg/kg partly and completely abolished these effects, respectively. However, lithium (100 mg/kg) increased BDNF expression level in control and sham REM SD rats with no significant changes in behavior. CONCLUSIONS: Chronic short-term REM SD may induce a mania-like model and lead to OCD-like behavior and irritability. In the present study, we demonstrated a putative rodent model of mania induced by chronic REM SD in female rats. We suggest that future studies should examine behavioral and mood changes following chronic REM SD in both sexes. Furthermore, the relationship between manic-like behaviors and chronic REM SD should be investigated.

YTHDF2 as a Mediator in BDNF-Induced Proliferation of Porcine Follicular Granulosa Cells.

In female mammals, the proliferation and apoptosis of granulosa cells (GCs) are critical in determining the fate of follicles and are influenced by various factors, including brain-derived neurotrophic factor (BDNF). Previous research has shown that BDNF primarily regulates GC proliferation through the PI3K/AKT, NF-kB, and CREB tumour pathways; however, the role of other molecular mechanisms in mediating BDNF-induced GC proliferation remains unclear. In this study, we investigated the involvement of the m6A reader YTH domain-containing family member 2 (YTHDF2) in BDNF-stimulated GC proliferation and its underlying mechanism. GCs were cultured in DMEM medium supplemented with varying BDNF concentrations (0, 10, 30, 75, and 150 ng/mL) for 24 h. The viability, number, and cell cycle of GCs were assessed using the CCK-8 assay, cell counting, and flow cytometry, respectively. Further exploration into YTHDF2's role in BDNF-stimulated GC proliferation was conducted using RT-qPCR, Western blotting, and sequencing. Our findings indicate that YTHDF2 mediates the effect of BDNF on GC proliferation. Additionally, this study suggests for the first time that BDNF promotes YTHDF2 expression by increasing the phosphorylation level of the ERK1/2 signalling pathway. This study offers a new perspective and foundation for further elucidating the mechanism by which BDNF regulates GC proliferation.

Association between Brain-Derived Neurotrophic Factor and Lipid Profiles in Acute Ischemic Stroke Patients.

Ischemic stroke, the most prevalent form of stroke, leads to neurological impairment due to cerebral ischemia and affects 55-90% of the population. Brain-derived neurotrophic factor (BDNF) plays a crucial role in the central nervous system and regulates cardiometabolic risk factors, including lipids. This single-center study aimed to explore the relationship between lipid profiles and BDNF levels in 90 patients who had experienced AIS for the first time. The results show that the high BDNF group (≥3.227 ng/mL) had significantly higher HbA1C and TG levels; ratios of TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C; and percentage of hyperlipidemia (60%) as well as lower levels of HDL-C, with an OR of 1.903 (95% CI: 1.187-3.051) for TG/HDL-C, 1.975 (95% CI: 1.188-3.284) for TC/HDL-C, and 2.032 (95% CI: 1.113-3.711) for LDL-C/HDL-C. Plasma BDNF levels were found to be significantly positively correlated with TG and negatively with HDL-C, with OR values of 1.017 (95% CI: 1.003-1.030) and 0.926 (95% CI: 0.876-0.978), respectively. TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C ratios are associated with BDNF levels in AIS patients. The results also indicate that, in AIS patients, higher BDNF levels are associated with lower HDL and higher TG concentrations.