Brain-derived Neurotrophic Factor Expression In Rats Research Articles

Angelica gigas ameliorate depression-like symptoms in rats following chronic corticosterone injection.

BackgroundRepeated injection of corticosterone (CORT) induces dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depression. We examined the effects of Angelica gigas extract (AGN) treatment in a rat model of depressive and anxiety-like behaviors, induced by chronic CORT exposure.MethodsMale rats received 10, 20, or 50 mg/kg AGN (i.p.) 30 min prior to a daily injection of CORT for 21 consecutive days. Activation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotropin-releasing factor in the hypothalamus.ResultsDaily AGN administration significantly reversed the depression and anxiety-like behavioral abnormalities. It also blocked increases in tyrosine hydroxylase expression in the locus coeruleus, and suppressed the decreased expression levels of brain-derived neurotrophic factor (BDNF) and its receptor TrkB mRNAs in the hippocampus.ConclusionsThese findings indicate that administration of AGN prior to high-dose exogenous CORT significantly improved helpless behaviors, possibly by modulating the central noradrenergic system and regulation of BDNF expression in rats. Thus, AGN may be a useful agent for the treatment or alleviation of psychiatric disorders associated with depression and anxiety disorders.

Knockdown of ventral tegmental area mu-opioid receptors in rats prevents effects of social defeat stress: Implications for amphetamine cross-sensitization, social avoidance, weight regulation and expression of brain-derived neurotrophic factor

Social defeat stress causes social avoidance and long-lasting cross-sensitization to psychostimulants, both of which are associated with increased brain-derived neurotrophic factor (BDNF) expression in the ventral tegmental area (VTA). Moreover, social stress upregulates VTA mu-opioid receptor (MOR) mRNA. In the VTA, MOR activation inhibits GABA neurons to disinhibit VTA dopamine neurons, thus providing a role for VTA MORs in the regulation of psychostimulant sensitization. The present study determined the effect of lentivirus-mediated MOR knockdown in the VTA on the consequences of intermittent social defeat stress, a salient and profound stressor in humans and rodents. Social stress exposure induced social avoidance and attenuated weight gain in animals with non-manipulated VTA MORs, but both these effects were prevented by VTA MOR knockdown. Rats with non-manipulated VTA MOR expression exhibited cross-sensitization to amphetamine challenge (1.0 mg/kg, i.p.), evidenced by a significant augmentation of locomotion. By contrast, knockdown of VTA MORs prevented stress-induced cross-sensitization without blunting the locomotor-activating effects of amphetamine. At the time point corresponding to amphetamine challenge, immunohistochemical analysis was performed to examine the effect of stress on VTA BDNF expression. Prior stress exposure increased VTA BDNF expression in rats with non-manipulated VTA MOR expression, while VTA MOR knockdown prevented stress-induced expression of VTA BDNF. Taken together, these results suggest that upregulation of VTA MOR is necessary for the behavioral and biochemical changes induced by social defeat stress. Elucidating VTA MOR regulation of stress effects on the mesolimbic system may provide new therapeutic targets for treating stress-induced vulnerability to substance abuse.

Antidepressive effect of sodium valproate involving suppression of corticotropin-releasing factor expression and elevation of BDNF expression in rats exposed to chronic unpredicted stress

Sodium valproate (VPA) is an antiepileptic drug and mood stabilizer used to treat bipolar disorders. Recently, other psychiatric uses for VPA have been based on its antidepressive and neuroprotective effects. In the current work, the antidepressive mechanism of VPA was investigated by studying the expression of brain-derived neurotrophic factor (BDNF) and hypothalamic-pituitary-adrenal axis function in rats exposed to a protocol of chronic unpredicted stress (CUS). Male Sprague-Dawley rats were divided into a vehicle-treated control group (no CUS+vehicle), a VPA-treated control group (no CUS+VPA), a vehicle-treated model group (CUS+vehicle), and a VPA-treated model group (CUS+VPA). VPA (300 mg/kg once daily) was administered to rats (no CUS+VPA and CUS+VPA) by an intragastric gavage, whereas the same volume of vehicle was administered to rats in the no CUS+vehicle and CUS+vehicle groups. Rat behavior, serum corticosterone level, and expression of BDNF in the hippocampus and corticotrophin-releasing factor in the hypothalamus were determined. Compared with the CUS+vehicle rats, the CUS+VPA rats showed a significant relief in depression-like behaviors and a decrease in the corticosterone level and corticotropin-releasing factor expression with increasing expression of BDNF. The results suggest that the antidepressive effect of VPA is at least partly related to improving hypothalamic-pituitary-adrenal axis function and elevating the expression of BDNF.

Resveratrol reverses the effects of chronic unpredictable mild stress on behavior, serum corticosterone levels and BDNF expression in rats

Depression is one of the most common neuropsychiatric disorders and has been associated with the neuroendocrine system and alterations in specific brain proteins. Resveratrol is a natural polyphenol enriched in polygonum cuspidatum and has diverse biological activities, including potent antidepressant-like effects. The present study attempts to explore the mechanisms underlying the antidepressant-like action of resveratrol by measuring serum corticosterone levels and the content of brain derived neurotrophic factor (BDNF) in the hippocampus and amygdala of rats exposed to the chronic unpredictable mild stress (CUMS). Male Wistar rats were subjected to the CUMS protocol for a period of 5 weeks to induce depressive-like behavior. Resveratrol treatment (20, 40 and 80mg/kg/i.p. 5 weeks) significantly reversed the CUMS-induced behavioral abnormalities (reduced sucrose preference, increased immobility time and decreased locomotor activity) and the elevated serum corticosterone levels observed in stressed rats. Additionally, 5-weeks of CUMS exposure significantly decreased BDNF levels in the hippocampus and amygdala, and was accompanied by decreased phosphorylation of extracellular signal-regulated kinase (pERK) and cAMP response element-binding protein (pCREB), while resveratrol treatment normalized these levels. All of these effects of resveratrol were essentially identical to that observed with the established antidepressant, desipramine. In conclusion, our study shows that resveratrol exerted antidepressant-like effects in CUMS rats, mediated in part by normalizing serum corticosterone levels while up-regulating pERK, pCREB and BDNF levels in the hippocampus and amygdala.

Peony glycosides reverse the effects of corticosterone on behavior and brain BDNF expression in rats

Repeated injections of corticosterone (CORT) induce the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depressive-like behavior. This study aimed to examine the antidepressant-like effect and the possible mechanisms of total glycosides of peony (TGP) in the CORT-induced depression model in rats. The results showed that the 3-week CORT injections induced the significant increase in serum CORT levels in rats. Repeated CORT injections also caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Moreover, it was found that brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus and frontal cortex were significantly decreased in CORT-treated rats. Treatment of the rats with TGP significantly suppressed the depression-like behavior and increased brain BDNF levels in CORT-treated rats. The results suggest that TGP produces an antidepressant-like effect in CORT-treated rats, which is possibly mediated by increasing BDNF expression in the hippocampus and frontal cortex.

Regulation of extracellular serotonin levels and brain-derived neurotrophic factor in rats with high and low exploratory activity

Serotonin (5-HT) system has a significant role in anxiety- and depression-related states and may be influenced by brain-derived neurotrophic factor (BDNF). This study examined extracellular 5-HT levels and expression of BDNF in rats with persistently low or high levels of exploratory activity (LE and HE, respectively). Baseline extracellular levels of 5-HT as assessed by in vivo microdialysis in conscious animals were similar in both groups in medial prefrontal cortex (PFC) and dentate gyrus (DG). No differences were found in parachloroamphetamine-induced 5-HT release in either region. However, LE animals had significantly higher levels of 5-HT transporter (5-HTT) binding in PFC and a larger increase in extracellular 5-HT levels after administration of citalopram (1 μM) into this area by retrograde dialysis. No difference in 5-HTT levels was found in hippocampus, while perfusion with citalopram was accompanied by a greater increase in extracellular 5-HT in the HE group in this brain region. LE-rats had higher levels of BDNF mRNA in the PFC but not hippocampus. In contrast, levels of nerve growth factor mRNA were similar in these brain regions of LE- and HE-rats. The differential regulation of 5-HT-ergic system in LE- and HE-rats in PFC and hippocampus may form the basis for their distinct anxiety-related behaviours.

Modulation of BDNF expression by electrical stimulation in hindlimb muscles of rats

AbstractTo evaluate the effects of electrical stimulation of the sciatic nerve on brain‐derived neurotrophic factor (BDNF) expression in the soleus and medial gastrocnemius muscles, we investigated temporal changes in BDNF protein and mRNA expression following electrical stimulation, and the optimal electrical stimulus paradigm for increasing BDNF expression in rats. The sciatic nerve was electrically stimulated with three different paradigms: 1 ms/40 Hz/30 min, 1 ms/40 Hz/40 Hz/5 min and 1 ms/1 Hz/30 min. Levels of BDNF protein and mRNA increased gradually over time after electrical stimulation in both muscles. Of the three stimulus paradigms, electrical stimulation at 1 ms/40 Hz/30 min produced the highest levels of BDNF protein and mRNA in both muscles, whereas stimulation at 1 ms/40 Hz/5 min produced the lowest expression levels. These results suggest that electrical stimulation could enhance neuronal plasticity by increasing BDNF production and paradigms of the stimulus can modulate the level of BDNF production.

Sex-specific effects of in utero manipulation of GABA A receptors on pre- and postnatal expression of BDNF in rats

Exposure to diazepam (DZ) during the last week of in utero development in rats induces neurobehavioral effects that do not become apparent in exposed animals until young adult ages. Some of the effects are sex specific. This study evaluated the hypothesis that late gestational exposure to DZ, a positive modulator of GABA(A) receptors, affects the developmental appearance of brain-derived neurotrophic factor (BDNF), an effect that could be linked to the later consequences of the exposure. Pregnant Long-Evans rats were injected with DZ (2.5 mg/kg) over gestation days 14-20, and their male and female offspring were evaluated for levels of BDNF mRNA and protein in the cerebral cortex and hypothalamus at fetal day 20 and at postnatal ages spanning birth to young adulthood. The effects of the exposure were sex and region specific. At fetal day 20 the expression of BDNF was reduced by about 20% in the hypothalamus of males only. The early exposure affected postnatal expression of BDNF in the hypothalamus only modestly, influencing the age-related profile in both sexes. Postnatal development of BDNF in the cerebral cortex was significantly affected by the in utero exposure in males only with mRNA levels lower in the exposed group and protein levels higher during juvenile ages. At adulthood, both levels were lower in DZ-exposed males. GABA serves a role as a trophic factor during early development, and these results suggest that manipulation of GABA(A) receptors during early development could interact with the developmental action of other trophic factors thereby leading to altered neural organization and later neurobehavioral dysfunction.