bdnf

Alzheimer’s disease (AD) is a brain disorder that slowly destroys memory through the destruction of neurons by activating BDNF/VEGF/FGF7 signaling. The purpose of this study was to investigate the effects of aerobic training and combination of resveratrol and fisetin on brain neurogenesis signaling pathways in Alzheimer’s mice.

In this experimental study, twenty-five C57BL/6J AD mice were randomized into 5 groups, including control, AD, AD+AT, AD+RSV+Fis, and AD+AT+RSV+Fis. The mice of the AD groups became AD by injecting amyloid-beta (Aβ1)-42 into the hippocampus. The AT protocol was five days per week for eight weeks before and after AD induction. RSV and Fis with concentrations of 25 mg/kg and 20 mg/kg were used, respectively. One-way analysis of variance was utilized to compare different groups, and Tukey’s post hoc test was employed at P≤0.05.

AD induction caused a significant decrease in the expression of BDNF/VEGF/FGF7 genes in hippocampal (P=0.001). AT and consumption of RSV+Fis significantly increased BDNF (P=0.001), VEGF (P=0.001), and FGF (P=0.001) in hippocampal.

It seems that AT and RSV+Fis, both alone and simultaneously, can help increase brain neurogenesis in elderly people with AD by increasing the expression of BDNF, VEGF, and FGF7 genes in the brain tissue.

Alzheimer's disease (AD) is a neurodegenerative condition characterized by progressive cognitive deterioration, including deficits in memory and other cognitive functions. Oxidative stress and free radical damage play significant roles in its pathogenesis. This study aimed to investigate the potential anti-inflammatory and neuroprotective effects of Pistacia atlantica gum (administered at doses of 50 and 100 mg/kg for 14 days) in a rat model of AD induced by aluminum chloride (AlCl3). Behavioral changes were assessed using open field, passive avoidance, and elevated plus maze tests. Additionally, nitrite levels, nuclear factor-kappa B (NF-κB), brain-derived neurotrophic factor (BDNF), and immunostaining were evaluated. Administration of P. atlantica gum significantly increased step-through latency in the passive avoidance test (P < 0.01 and P < 0.001), enhanced mobility in the open field test (P < 0.01 and P < 0.001), and reduced anxiety-like behaviors in the elevated plus maze (P < 0.001) compared to the AlCl3 group. Treatment with the gum partially normalized the elevated levels of NF-κB and the decreased levels of BDNF caused by AlCl3 exposure. Our findings suggest that P. atlantica gum administration may alleviate oxidative stress, neuroinflammation, and cognitive impairment in AD rats.

Three physiological processes interact: sleep, learning, and stress. It is essential to understand how stress affects and interacts with the link between sleep, learning, and memory since it has long been recognized that sleep plays a crucial role in memory consolidation and learning. Through naloxone injection in the Baso Lateral Amygdala (BLA), this study intends to shed light on the interactions between stress, learning, and sleep, as well as the function of the opioid system and its impact on Brain-Derived Neurotrophic Factor (BDNF) production in the hippocampus.

Male Wistar rats (n=77) in eleven groups were implanted with electroencephalogram (EEG) and electromyography (EMG) recording electrodes, and the BLA area was bilaterally cannulated. Recordings of Rapid Eye Movement (REM) and Non-Rapid Eye Movement (NREM) sleep and wakefulness steps were made for the three hours prior to and three hours following the implementation of the immobility stress protocol and learning with the Barnes maze for three consecutive days. Also, the animals’ memory was tasted 48 hr later. Before the stress and learning procedure, naloxone was injected into each BLA three times in a row at a dosage of 0.05 μg or 0.1 μg in a volume of 0.5 μl. A molecular biomarker of learning and stress, BDNF, was also examined.

The study demonstrated that the immobility stress model lowers REM and NREM sleep. On the other hand, putting the learning technique into practice results in more REM and NREM sleep, and stress situations do not stop this rise after learning. Naloxone injections in the BLA region also enhance learning and memory, preventing stress-related REM and NREM sleep loss. Additionally, stress lowers BDNF expression in the hippocampal region. BDNF expression rises in the hippocampus throughout the learning process, and naloxone administration in the BLA area also raises BDNF expression in the hippocampus.

Stress generally reduces REM, NREM, and BDNF expression in the hippocampal region. Under stress, using the learning protocol increases REM, NREM sleep, and BDNF. Naloxone injection in BLA improves memory and learning, reducing stress-induced memory loss.

The aim of this study is to investigate the possible role of the hippocampal BDNF-PI3K-AKT signaling pathway in the antidepressant-like activity of ellagic acid (EA) in mice.

Male BALB/C mice were divided into 5 groups; vehicle (0.1 ml/day), sertraline (5mg/kg), EA (1 mg/kg), EA+BKM120 (PI3K inhibitor), EA+MK2206 (AKT inhibitor). EA, sertraline and vehicle were injected intraperitoneally for 14 days. Locomotor activity was determined by open field test. The tail suspension test was used to detect the antidepressant-like effect. After behavioral tests, hippocampal tissue was obtained and Western blot analyzes were performed for BDNF and pAKT1. 

Sertraline and EA provided a reduction in immobility time in the tail suspension test when compared with the control group. BKM120 and MK2206 administration reversed this effect of EA. No statistical difference was found between groups in terms of locomotor activity. EA treatment caused an increase in hippocampal BDNF and pAKT1 levels in mice. While inhibitory agent administrations did not affect the increase of BDNF induced by EA, MK2206 administration reversed the increase in pAKT1 observed with EA.

It has shown that EA has an antidepressant-like effect in mice without changing locomotor activity, and this effect may be mediated by the BDNF-PI3K-AKT signaling pathway.

Alzheimer's disease (AD) is associated with a marked reduction in brain-derived neurotrophic factor (BDNF) and fibronectin 1 (Fn1). This study investigates the effects of fisetin supplementation combined with high-intensity interval training (HIIT) on these neurogenesis markers in an aged mouse model of AD.  In this experimental study, 30 aged C57BL/6 mice (weight: 30 g) with AD were randomly assigned to one of the five groups: (1) Control, (2) AD, (3) AD + Fisetin, (4) AD + HIIT, and (5) AD + HIIT + Fisetin. Alzheimer's disease was induced in the AD groups by injecting amyloid-beta (Aβ1-42) into the hippocampus. The HIIT protocol consisted of a 10-minute warm-up at 50-55% VO2 max, followed by seven intervals, each comprising 4 minutes at 80-90% VO2 max and 3 minutes at 65-75% VO2 max. Fisetin was administered at 20 mg/kg for eight weeks. Data were analyzed using one-way ANOVA with a significance level of P ≤ 0.05.  Significant differences were observed in BDNF, Fn1, and Aβ gene expression levels across the five groups of aged mice (p < 0.001). BDNF and Fn1 expression were significantly reduced in the AD groups compared to the healthy controls (p < 0.001). However, their expression levels increased significantly in the AD + Training + Fisetin, AD + Training, and AD + Fisetin groups compared to the AD-only group (p < 0.001). The AD + Training + Fisetin group exhibited the highest expression levels, followed by the AD + Training and AD + Fisetin groups (p < 0.001). Aβ expression was significantly reduced in all intervention groups, with the AD + Training + Fisetin group showing the most substantial decrease (p < 0.001).  Combining HIIT and fisetin supplementation may promote cerebral neurogenesis in AD by reducing Aβ levels and enhancing BDNF and Fn1 gene expression. Notably, the combined intervention of HIIT and fisetin exhibits a more significant effect than either HIIT or fisetin alone, with HIIT being more effective than fisetin as a standalone treatment. Thus, the combination of HIIT and fisetin appears to be the most effective complementary approach for managing this disease.

Methamphetamine is a commonly abused drug, and its neurotoxic effects have increased in recent years. There is growing evidence that buprenorphine, a widely used drug for pain management, reduces the harmful effects of addiction and is effective in treating opioid dependence.

This study aimed to investigate the interaction between methamphetamine and buprenorphine on analgesia and the expression of BDNF and CREB genes in the spinal cords of rats.

In this study, 56 male Wistar rats (200 ± 50 g) were randomly assigned to eight groups: Control, sham, methamphetamine, two buprenorphine groups, two methamphetamine + buprenorphine groups, and a deprivation group. A one-way ANOVA test was used to analyze the data.

Intraperitoneal injection of methamphetamine (10 mg/kg) induced analgesia (P < 0.05) and increased CREB gene expression in the lumbar spinal cord (P < 0.01), whereas buprenorphine alone (6 and 10 mg/kg) did not induce significant analgesia or alter BDNF gene expression in the spinal cord. Pharmacological interactions revealed that buprenorphine (6 and 10 mg/kg, i.p.) enhanced the analgesic effect of methamphetamine. Additionally, while the lower dose of buprenorphine reduced methamphetamine's effect on CREB gene expression (P < 0.05), the higher dose potentiated the effect of methamphetamine on BDNF gene expression (P < 0.01) without significantly affecting CREB gene expression.

The findings suggest that buprenorphine may enhance the analgesic effects of acute methamphetamine administration and modulate gene expression in the lumbar spinal cord of male Wistar rats.

Melissa officinalis (MO) hydroalcoholic extract has shown neuroprotective effects. We assess the possible therapeutic effects of Melissa officinalis extract (MOE) on blood biochemical and Brain-Derived Neurotrophic Factor (BDNF) levels as well as neurobehavioral consequences of high-fat-diet (HFD)-induced obese rats. Eighty male Wistar rats weighing between 180 and 220 g were divided into two groups at the beginning of the experiment and fed with normal diet (ND) or HFD for 5 weeks. Then, each group was divided into four subgroups (10 rats in each group) and treated daily with MOE (50, 100, 150 mg/kg, intraperitoneal) or vehicle for another two weeks. At the end of the experiments, fasting blood glucose (FBG), blood lipid profile, and serum brain-derived neurotrophic factor (BDNF) levels were measured. The sucrose preference test (anhedonia and depression), open field test (locomotor), elevated plus maze (anxiety), Y-maze (working memory), and Morris water maze test (spatial memory) were done. Feeding with HFD for 7 weeks caused obesity, anhedonia, anxiety, depression and learning and memory disorders in rats and a decrease in serum BDNF level. Administration of MOE at 100 or 150 mg/kg to HFD-fed rats decreased weight gain, FBG, and serum levels of total low-density lipoprotein cholesterol and increased serum BDNF levels. It also improved changes in locomotor activity, anxiety, depression, and learning and memory in HFD-fed rats. The results show that MOE has a therapeutic effect on model rats with HFD-induced metabolic and neurobehavioral abnormalities through regulation of BDNF secretion.

Traumatic brain injury (TBI) remains a primary cause of mortality and is a significant contributor to various impairments, including somatosensory and cognitive deficits. The prevention and management of injuries require regular daily exercise. In this research, we examined the impact of eight weeks of aerobic exercise on neurological outcomes, brain water content (BWC), blood-brain barrier (BBB) permeability, electrophysiological characteristics, and concentrations of brain-derived neurotrophic factor (BDNF) in an experimental model of TBI.

Sixty-four male Wistar rats were divided into four groups: Control, Training, TBI, and Training-TBI. TBI was induced using the Marmarou method. After TBI induction, eight weeks of aerobic exercise were performed using a five-line animal treadmill. Then, the rats’ memory and learning were assessed using the Morris water maze. Electrodes were implanted in the skulls of anesthetized rats for single-unit recording. Neurological scores, BWC, BBB permeability, and cerebral tissue BDNF concentrations were measured 48 hours after exercise. Statistical analysis was conducted using one-way ANOVA, followed by Tukey’s post hoc test for multiple comparisons. P values < 0.05 were considered statistically significant.

Aerobic exercise significantly reversed the decrement of neurological scores, the neuronal firing rate of the hippocampus, increments of BWC, cognition deficits, and cerebral tissue Evans blue concentration after TBI compared with control. It also increased cerebral tissue BDNF, which had significantly decreased in TBI.

Our results suggest that through BDNF increment, aerobic exercise exerts neuroprotective effects on memory impairment and the decrement of neuronal firing rate caused by TBI.

Prenatal stress (PS) can adversely affect cognitive and psychological functions in the offspring. This study aimed to determine the effect of PS and extremely low-frequency electromagnetic field (ELF-EMF) on spatial memory, serum corticosterone, brain-derived neurotrophic factor (BDNF) concentrations, and hippocampal BDNF levels in adult male offspring. 

Female Wistar rats were randomly divided into four groups (n=6): Control, Stress, ELF-EMF (exposure to ELF-EMF), and S+EMF (simultaneous exposure to stress and the ELF-EMF) groups. Animals received interven-tions for 21 days before and 21 days during pregnancy (a total of 42 days). On the offspring’s 90th postnatal day (PND), spatial memory was tested using Morris Water Maze, serum Corticosterone and BDNF levels were measured by the ELISA method, and hippocampal BDNF levels were measured by Western blotting. 

PS did not affect spatial memory in the adult male offspring; however, it significantly (P<0.05) increased se-rum corticosterone levels compared to the control and EMF groups. Simultaneous induction of stress with ELF-EMF disrupted the memory acquisition phase. Serum and hippocampal BDNF levels increased signifi-cantly (P<0.05) in the EMF group compared to the stress group. 

Based on our findings, PS can increase serum corticosterone levels without affecting spatial memory. Howev-er, induction of ELF-EMF with stress has a destructive effect on spatial memory with no change in the corti-costerone levels. Compared to stress, prenatal exposure to ELF-EMF increases serum and hippocampal BDNF levels. Further studies are needed to determine the underlying mechanisms of these findings.

Adult neurogenesis, the process of generating new neurons, continues throughout life. Unfortunately, this process is insufficient in pathological conditions and needs to be promoted. Crocin, the active component of saffron, affects neurogenesis in vivo and in vitro. We aimed to investigate the enhancing effects of crocin on the neurogenesis of adipose-derived mesenchymal stem cells in the presence of retinoic acid, as well as the molecular pathways involved. 

Differentiation capacities and stemness potential of harvested ADSCs were evaluated by differentiating into osteocytes and adipocytes, and expression of mesenchymal CD markers by flow cytometry. The optimum dose of crocin was assessed with an MTT assay. Crocin, retinoic acid, CREB/BDNF, and Notch inhibitors and their combination were added to the culture medium. Jag1, Hes1, Notch, and BDNF gene expression were analyzed by RT-PCR on days 7, 14, and 21, while CREB, DCX, SOX2, and NeuN expression were analyzed by immunofluorescence.

Expression of mesenchymal CD markers as well as adipogenic and osteogenic differentiation confirmed the origin and properties of ADSCs. The optimal dose of crocin was 1 mM. Crocin significantly (P<0.05) increased, while inhibitors (DATP&Naphthol) significantly (P<0.05) decreased Jag1, Hes1, Notch, and BDNF expression. Immunofluorescent assessments showed that expression of DCX, BDNF, NeuN, and Sox2 proteins increased significantly (P<0.05) after crocin administration and decreased significantly (P<0.05) after inhibitor administration.

Crocin can be used as an enhancer for neural differentiation of MSCs in vitro in the presence of retinoic acid. The mechanism is proposed through Notch and CREB/BDNF signaling pathways.

Maternal separation (MS) is a well-characterized model of early life stress, based on the postnatal disruption of the mother-infant interaction. Studies on rodents have demonstrated that MS, as an early adverse life event, leads to spatial memory deficits and lasting changes in brain plasticity. Here, we review data from animal studies regarding the impact of MS on long-term potentiation (LTP). Evidence shows that animal models are useful for evaluating the effects of MS on LTP. Overall, studies suggest that MS impairs LTP.

 Chlorpyrifos (CPF) is an insecticide and has a wide range of applications in the world. The purpose of this research was to investigate the effect of 4-week aerobic exercise and eugenol supplementation on the brain-derived neurotrophic factor/phosphoinositide 3-kinase (BDNF/PI3K) pathway on the skeletal muscle of male rats poisoned with CPF.

 Overall, 12-week-old female rats were used in this experimental research. The rats were randomly divided into 7 groups (8 rats in each group), including healthy control, toxic control, poison solvent, corn oil solvent, poisoned+eugenol, poisoned+aerobic exercise, and poisoned+aerobic exercise+eugenol. Moderate training in the range of 50%-60% VO2max, including 5 training sessions per week (treadmill). Poisoning was performed with CPF poison with a dose of 3 mg/kg. The dose of eugenol was determined to be 250 mg/kg. Finally, a one-way analysis of variance and Tukey’s post hoc test were employed to check the difference between groups.

 The expression of PI3K and BDNF in the poisoned control group was lower than that in the healthy control group (P=0.049 and P=0.001, respectively). In addition, the expression of PI3K and BDNF was higher in the poisoned+eugenol+exercise group compared to the poisoned control group (P=0.009 and P=0.03, respectively). The corn solvent group also had a higher PI3K and BDNF expression in comparison to the poisoned control group (P=0.025 and P=0.01, respectively). Eventually, there was no significant difference among other groups.

 Exercise and eugenol increased PI3K and BDNF expression. It is thought that exercise and consumption of eugenol in poisoned rats reduces damage and improves muscle function and the BDNF/PI3K signaling pathway.