Dose-related effects of venlafaxine on pCREB and brain-derived neurotrophic factor (BDNF) in the hippocampus of the rat by chronic unpredictable stress

Background: The molecular pathogenesis of depression and psychopharmacology of antidepressants remain elusive. Recent hypotheses suggest that changes in neurogenesis and plasticity may underlie the aetiology of depression. The hippocampus is affected by depression and shows neuronal remodelling during adulthood.Objective: The present study on the adult rat hippocampus, was to evaluate the dose-related effects of chronic venlafaxine on the expression of brain-derived neurotrophic factor (BDNF) and phosphorylated cyclic-AMP response element binding protein (pCREB).Methods: Sprague-Dawley rats were exposed to a variety of chronic unpredictable stressors (CUSs) to establish a depression model. Rats were treated for either 14 or 28 days with venlafaxine (5 and 10 mg/kg, respectively). The hippocampal expression of pCREB and BDNF mRNA and protein was assessed by using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction (RT-PCR).Results: Rats subjected to CUS procedure consumed less sucrose solution compared with non-stressed rats. The CUS influenced exploratory activity resulting in a reduction of the motility counts. Chronic low dose (5 mg/kg, 14 and 28 days), but not high dose (10 mg/kg, 14 and 28 days) of venlafaxine treatment increased the expression of pCREB and BDNF mRNA and protein in the CUS rat hippocampus.Conclusion: Neuronal plasticity-associated proteins such as pCREB and BDNF play an important role both in stress-related depression and in antidepressant effect.

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Stressor-Specific Regulation of Distinct Brain-Derived Neurotrophic Factor Transcripts and Cyclic AMP Response Element-Binding Protein Expression in the Postnatal and Adult Rat Hippocampus

Neuropsychopharmacology ◽

10.1038/sj.npp.1301276 ◽

2006 ◽

Vol 32 (7) ◽

pp. 1504-1519 ◽

Cited By ~ 121

Author(s):

Amrita Nair ◽

Krishna C Vadodaria ◽

Sunayana B Banerjee ◽

Madhurima Benekareddy ◽

Brian G Dias ◽

...

Keyword(s):

Cyclic Amp ◽

Protein Expression ◽

Neurotrophic Factor ◽

Brain Derived Neurotrophic Factor ◽

Rat Hippocampus ◽

Response Element ◽

Adult Rat ◽

Element Binding Protein ◽

Cyclic Amp Response Element ◽

Specific Regulation

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Brain-derived neurotrophic factor enhances spontaneous sleep in rats and rabbits

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1999.276.5.r1334 ◽

1999 ◽

Vol 276 (5) ◽

pp. R1334-R1338 ◽

Cited By ~ 18

Author(s):

Tetsuya Kushikata ◽

Jidong Fang ◽

James M. Krueger

Keyword(s):

Growth Factors ◽

Neurotrophic Factor ◽

Brain Temperature ◽

Brain Derived Neurotrophic Factor ◽

Normal Brain ◽

Sprague Dawley ◽

Sleep Regulation ◽

Bdnf Mrna ◽

Sprague Dawley Rats ◽

Intracerebroventricular Injections

Various growth factors are involved in sleep regulation. Brain-derived neurotrophic factor (BDNF) belongs to the neurotrophin family; it and its receptors are found in normal brain. Furthermore, cerebral cortical levels of BDNF mRNA have a diurnal variation and increase after sleep deprivation. Therefore, we investigated whether BDNF would promote sleep. Twenty-four male Sprague-Dawley rats (320–380 g) and 25 male New Zealand White rabbits (4.5–5.5 kg) were surgically implanted with electroencephalographic (EEG) electrodes, a brain thermistor, and a lateral intracerebroventricular cannula. The animals were injected intracerebroventricularly with pyrogen-free saline and, on a separate day, one of the following doses of BDNF: 25 or 250 ng in rabbits; 10, 50, or 250 ng in rats. The EEG, brain temperature, and motor activity were recorded for 23 h after the intracerebroventricular injections. BDNF increased time spent in non-rapid eye movement sleep (NREMS) in rats and rabbits and REMS in rabbits. Current results provide further evidence that various growth factors are involved in sleep regulation.

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Antidepressant-Like Effects and Cognitive Enhancement of Coadministration of Chaihu Shugan San and Fluoxetine: Dependent on the BDNF-ERK-CREB Signaling Pathway in the Hippocampus and Frontal Cortex

BioMed Research International ◽

10.1155/2020/2794263 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Lijing Yan ◽

Xia Xu ◽

Zhenyu He ◽

Sheng Wang ◽

Linlin Zhao ◽

...

Keyword(s):

Cognitive Function ◽

Frontal Cortex ◽

Signaling Pathway ◽

Low Dose ◽

Antidepressant Effect ◽

Control Group ◽

High Dose ◽

Mild Stress ◽

Sprague Dawley ◽

Bdnf Mrna

Background. Fluoxetine (FLU) is the first-line and widely used medication for depression; however, FLU treatment is almost ineffective in 30%-40% of patients with depression. In addition, there are some problems in FLU treatment, such as delayed efficacy, large side effects, and poor tolerance. Chaihu Shugan San (CSS) is a classic and effective antidepressant Chinese herbal medicine that has been used in China for thousands of years. CSS or coadministration of CSS and FLU has become one of the most recommended methods in the treatment of depression in China. However, the specific pathways of CSS and coadministration of CSS and FLU for antidepressant are still unclear. Objective. This study was designed to evaluate the antidepressant effects of CSS and coadministration of CSS and FLU. Methods. The chronic unpredictable mild stress (CUMS) rat model was used to simulate depression. 120 healthy adult male Sprague-Dawley (SD) rats were randomly divided into seven groups: the control group, CUMS group, low-dose CSS group, high-dose CSS group, FLU group, coadministration of low-dose CSS and FLU group, and coadministration of high-dose CSS and FLU group. The rats in different groups were given different interventions. Then, the depression-like behavior and cognitive function were evaluated by the sucrose preference test (SPT), forced swimming test (FST), open field test (OFT), and Y-maze test. What is more, the antidepressant mechanism of CSS and coadministration of CSS and FLU were studied through BDNF mRNA, ERK mRNA, CREB mRNA, BDNF, p-ERK/ERK, and p-CREB/CREB levels in the hippocampus and frontal cortex by Western blot and RT-PCR. Results. Compared with the CUMS group, CSS and coadministration of CSS and FLU could alleviate the depressive symptoms and improve cognitive function in CUMS rats (p<0.05); CSS and coadministration of CSS and FLU could increase the expression of BDNF, p-CREB/CREB, p-ERK/ERK, and BDNF mRNA, CREB mRNA, and ERK mRNA in the hippocampus and frontal cortex (p<0.05). Besides, the high-dose CSS combined with the fluoxetine group was significantly better than the fluoxetine group and CSS group (p<0.05). Discussion and Conclusion. Finally, we found that both CSS and coadministration of CSS and FLU play an antidepressant role, which may be due to the regulation of the BDNF/ERK/CREB signaling pathway in the hippocampus and frontal cortex. Among them, the coadministration of CSS and FLU can enhance the antidepressant effect of CSS or FLU alone, and the underlying mechanism needs further investigation.

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