scholarly journals Chronic Mild Stress Modulates Activity-Dependent Transcription of BDNF in Rat Hippocampal Slices

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Raffaella Molteni ◽  
Andrea C. Rossetti ◽  
Elisa Savino ◽  
Giorgio Racagni ◽  
Francesca Calabrese
Keyword(s):  
Intracellular Signaling ◽  
Ex Vivo ◽  
Hippocampal Slices ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Mrna Levels ◽  
Bdnf Expression ◽  
Bdnf Mrna ◽  
Activity Dependent ◽  
Bdnf Transcription

Although activity-dependent transcription represents a crucial mechanism for long-lasting experience-dependent changes in the hippocampus, limited data exist on its contribution to pathological conditions. We aim to investigate the influence of chronic stress on the activity-dependent transcription of brain-derived neurotrophic factor (BDNF). Theex vivomethodology of acute stimulation of hippocampal slices obtained from rats exposed to chronic mild stress (CMS) was used to evaluate whether the adverse experience may alter activity-dependent BDNF gene expression. CMS reduces BDNF expression and that acute depolarization significantly upregulates total BDNF mRNA levels only in control animals, showing that CMS exposure may alter BDNF transcription under basal conditions and during neuronal activation. Moreover, while the basal effect of CMS on total BDNF reflects parallel modulations of all the transcripts examined, isoform-specific changes were found after depolarization. This different effect was also observed in the activation of intracellular signaling pathways related to the neurotrophin. In conclusion, our study discloses a functional alteration of BDNF transcription as a consequence of stress. Being the activity-regulated transcription a critical process in synaptic and neuronal plasticity, the different regulation of individual BDNF promoters may contribute to long-lasting changes, which are fundamental for the vulnerability of the hippocampus to stress-related diseases.

scholarly journals A novel enhancer that regulates Bdnf expression in developing neurons

2021 ◽  
Author(s):  
Emily Brookes ◽  
Ho Yu Alan Au ◽  
Wazeer Varsally ◽  
Christopher Barrington ◽  
Suzana Hadjur ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Neuronal Development ◽  
Nuclear Periphery ◽  
Mrna Levels ◽  
Bdnf Expression ◽  
Bdnf Mrna ◽  
Enhancer Activity ◽  
Mediated Effects ◽  
Developing Neurons ◽  
Activity Dependent

Brain derived neurotrophic factor (BDNF) is a critical secreted peptide that promotes neuronal differentiation and survival, and its downregulation is implicated in many neurological disorders. Here, we investigated the regulation of the mouse Bdnf gene in cortical neurons and identified a novel enhancer that promotes the expression of many Bdnf transcript variants during differentiation, increasing total Bdnf mRNA levels. Enhancer activity contributes to Bdnf-mediated effects on neuronal clustering and activity-dependent dendritogenesis. During Bdnf activation, enhancer-promoter contacts increase, and the region moves away from the repressive nuclear periphery. Our findings suggest that changes in nuclear structure may contribute to the expression of essential growth factors during neuronal development.

scholarly journals Haloperidol and aripiprazole impact on the BDNF and glucocorticoid receptor levels in the rat hippocampus and prefrontal cortex: effect of the chronic mild stress

2021 ◽  
Vol 55 (3) ◽  
pp. 153-162
Author(s):  
Jana Osacka ◽  
Romana Koprdova ◽  
Andrej Tillinger ◽  
Zdenko Pirnik ◽  
Alexander Kiss
Keyword(s):  
Prefrontal Cortex ◽  
Weight Gain ◽  
Glucocorticoid Receptor ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Typical Antipsychotic ◽  
Mrna Levels ◽  
Frozen Sections ◽  
Bdnf Mrna ◽  
The Brain

Abstract Objective. Changes in the brain derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR) expression in the prefrontal cortex (PFC) and hippocampus (HIP) are associated with psychiatric diseases and stress response. Chronic mild stress (CMS) may alter BDNF as well as GR levels in both the PFC and the HIP. The aim of the present study was to find out whether chronic treatment with a typical antipsychotic haloperidol (HAL) and an atypical antipsychotic aripiprazole (ARI) may modify the CMS effect on the BDNF and GR expression in the above-mentioned structures. Methods. The rats were exposed to CMS for 3 weeks and from the 7th day of CMS injected with vehicle (VEH), HAL (1 mg/kg) or ARI (10 mg/kg) for 4 weeks. BDNF and GR mRNA levels were established in the PFC and the HIP by Real Time PCR, whereas, PFC and HIP samples were obtained by punching them from 500 µm thick frozen sections. C-Fos immunoreactivity was analyzed in the PFC and the HIP on 30 µm thick paraformaldehyde fixed sections. Weight gain and corticosterone (CORT) levels were also measured. Results. The CMS and HAL suppressed the BDNF and GR mRNA levels in the PFC. In the HIP, CMS elevated BDNF mRNA levels that were suppressed by HAL and ARI treatments. The CMS decreased the c-Fos immunoreactivity in the PFC in both HAL- and ARI-treated animals. In the HIP, HAL increased the c-Fos immunoreactivity that was again diminished in animals exposed to CMS. Stressed animals gained markedly less weight until the 7th day of CMS, however, later their weight gain did not differ from the unstressed ones or was even higher in CMS+HAL group. Un-stressed HAL and ARI animals gained less weight than the VEH ones. Neither CMS nor HAL/ARI affected the plasma CORT levels. Conclusion. The present data indicate that HAL and ARI in the doses 1 mg/kg or 10 mg/kg, respectively, does not modify the effect of the CMS preconditioning on the BDNF and GR mRNA levels in the PFC or the HIP. However, HAL seems to modify the CMS effect on the HIP activation.

scholarly journals Deficiency in Androgen Receptor Aggravates the Depressive-Like Behaviors in Chronic Mild Stress Model of Depression

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1021 ◽  
Author(s):  
Hung ◽  
Huang ◽  
Chang ◽  
Kang
Keyword(s):  
Androgen Receptor ◽  
Chronic Mild Stress ◽  
Mapk Signaling ◽  
Mild Stress ◽  
Therapeutic Approaches ◽  
Bdnf Expression ◽  
Bdnf Mrna ◽  
Major Depressive ◽  
Mouse Hippocampus ◽  
The Brain

While androgen receptor (AR) and stress may influence the development of the major depressive disorder (MDD), the detailed relationship, however, remains unclear. Here we found loss of AR accelerated development of depressive-like behaviors in mice under chronic mild stress (CMS). Mechanism dissection indicated that AR might function via altering the expression of miR-204-5p to modulate the brain-derived neurotrophic factor (BDNF) expression to influence the depressive-like behaviors in the mice under the CMS. Adding the antiandrogen flutamide with the stress hormone corticosterone can additively decrease BDNF mRNA in mouse hippocampus mHippoE-14 cells, which can then be reversed via down-regulating the miR-204-5p expression. Importantly, targeting this newly identified AR-mediated miR-204-5p/BDNF/AKT/MAPK signaling with small molecules including 7,8-DHF and fluoxetine, all led to alter the depressive-like behavior in AR knockout mice under CMS exposure. Together, results from these preclinical studies conclude that decreased AR may accelerate the stress-induced MDD via altering miR-204-5p/BDNF/AKT/MAPK signaling, and targeting this newly identified signaling may help in the development of better therapeutic approaches to reduce the development of MDD.

Expression of the BDNF gene in the developing visual system of the chick

Development ◽  
1994 ◽  
Vol 120 (6) ◽  
pp. 1643-1649 ◽  
Author(s):  
K.H. Herzog ◽  
K. Bailey ◽  
Y.A. Barde
Keyword(s):  
Visual System ◽  
Ganglion Cells ◽  
Mrna Levels ◽  
Retinal Ganglion ◽  
Bdnf Gene ◽  
Bdnf Mrna ◽  
Optic Stalk ◽  
Copy Numbers ◽  
Activity Dependent

Using a sensitive and quantitative method, the mRNA levels of brain-derived neurotrophic factor (BDNF) were determined during the development of the chick visual system. Low copy numbers were detected, and BDNF was found to be expressed in the optic tectum already 2 days before the arrival of the first retinal ganglion cell axons, suggesting an early role of BDNF in tectal development. After the beginning of tectal innervation, BDNF mRNA levels markedly increased, and optic stalk transection at day 4 (which prevents subsequent tectal innervation) was found to reduce the contralateral tectal levels of BDNF mRNA. Comparable reductions were obtained after injection of tetrodotoxin into one eye, indicating that, already during the earliest stages of target encounter in the CNS, the degree of BDNF gene expression is influenced by activity-dependent mechanisms. BDNF mRNA was also detected in the retina itself and at levels comparable to those found in the tectum. Together with previous findings indicating that BDNF prevents the death of cultured chick retinal ganglion cells, these results support the idea that the tightly controlled expression of the BDNF gene might be important in the co-ordinated development of the visual system.

Chronic mild stress induces widespread decreases in thyroid hormone α1 receptor mRNA levels in brain—Reversal by imipramine

2009 ◽  
Vol 34 (2) ◽  
pp. 281-286 ◽  
Author(s):  
Edward J. Stein ◽  
Nylson G. da Silveira Filho ◽  
Danilo C. Machado ◽  
Débora C. Hipólide ◽  
Karen Barlow ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Chronic Mild Stress ◽  
Mild Stress ◽  
Mrna Levels ◽  
Receptor Mrna

Differential Expression of MicroRNAs and miR-206-Mediated Downregulation of BDNF Expression in the Rat Fetal Brain Following Maternal Hypothyroidism

2018 ◽  
Vol 50 (09) ◽  
pp. 696-703 ◽  
Author(s):  
Qian Xing ◽  
Zhongyan Shan ◽  
Yun Gao ◽  
Jingyuan Mao ◽  
Xiu Liu ◽  
...  
Keyword(s):  
Real Time ◽  
Fetal Brain ◽  
Mirna Expression Profile ◽  
Control Group ◽  
Mrna Levels ◽  
Neonatal Rats ◽  
Bdnf Expression ◽  
Bdnf Mrna ◽  
Significant Difference ◽  
Brain Tissues

AbstractTo investigate the mechanism responsible for the neurological alterations, miRNA expression profile and brain-derived neurotrophic factor (BDNF) were evaluated in brain tissues of fetal or neonatal rats and from maternal rats with hypothyroidism. Ninety female Wistar rats were divided into a control and a hypothyroid group, which were mated. Brain samples of the offspring were obtained at maternal embryonic day (E) E13 and E17 as well as postnatal day (P) P0 and P7, and the hippocampus and cortex were separated at P7. BDNF mRNA at E13 was tested by real-time PCR and protein expression by Western blot. Luciferase assays were used to confirm that miR-206 targets the 3′-untranslated region (3′-UTR) of BDNF. In the brain tissues of fetal and neonatal rats from maternal rats with hypothyroidism, differentiation miRNAs profile were found at E13, E17, P0, and P7. Compared with the control group, miR-206 levels in the hypothyroidism group were increased by 3.1-fold by micro-array, and were higher as measured by SYBR green real-time qRT–PCR (p<0.01). There was no significant difference in the BDNF mRNA levels at E13 between the hypothyroidism group and the control group (1.767±0.477 vs. 1.798±0.462, respectively; p>0.05), but pro-BDNF and mature BDNF protein levels in the hypothyroid group at E13 were significantly lower than those in the control group (p<0.05). miR-206 targeted 3′-UTR of BDNF. Our data highlight the role of miR-206 as a post-transcriptional inhibitor of BDNF at E13 in pregnant hypothyroid rats.

scholarly journals Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus

2018 ◽  
Vol 115 (15) ◽  
pp. E3549-E3558 ◽  
Author(s):  
John Marshall ◽  
Xiao-zhong Zhou ◽  
Gang Chen ◽  
Su-qing Yang ◽  
Ya Li ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Adaptor Protein ◽  
Chronic Mild Stress ◽  
Mapk Signaling ◽  
Mild Stress ◽  
Limbic Structure ◽  
Double Knockout ◽  
Bdnf Expression ◽  
Functional Studies

Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 and Gαi3 subunits of heterotrimeric G proteins are down-regulated in the hippocampus, a key limbic structure associated with major depressive disorder. We provide evidence that Gαi1 and Gαi3 (Gαi1/3) are required for the activation of TrkB downstream signaling pathways. In mouse embryonic fibroblasts (MEFs) and CNS neurons, Gαi1/3 knockdown inhibited BDNF-induced tropomyosin-related kinase B (TrkB) endocytosis, adaptor protein activation, and Akt–mTORC1 and Erk–MAPK signaling. Functional studies show that Gαi1 and Gαi3 knockdown decreases the number of dendrites and dendritic spines in hippocampal neurons. In vivo, hippocampal Gαi1/3 knockdown after bilateral microinjection of lentiviral constructs containing Gαi1 and Gαi3 shRNA elicited depressive behaviors. Critically, exogenous expression of Gαi3 in the hippocampus reversed depressive behaviors in CMS mice. Similar results were observed in Gαi1/Gαi3 double-knockout mice, which exhibited severe depressive behaviors. These results demonstrate that heterotrimeric Gαi1 and Gαi3 proteins are essential for TrkB signaling and that disruption of Gαi1 or Gαi3 function could contribute to depressive behaviors.

scholarly journals Nicotine induces chromatin remodelling through decreases in the methyltransferases GLP, G9a, Setdb1 and levels of H3K9me2

2013 ◽  
Vol 16 (5) ◽  
pp. 1129-1138 ◽  
Author(s):  
Kayla A. Chase ◽  
Rajiv P. Sharma
Keyword(s):  
Gene Expression ◽  
Mrna Expression ◽  
Human Lymphocyte ◽  
Histone H3 ◽  
Lymphocyte Culture ◽  
Mrna Levels ◽  
Bdnf Mrna ◽  
Epigenetic Effects ◽  
Cortical Neuronal Culture ◽  
Bdnf Transcription

Abstract Studies examining the epigenetic effects of nicotine are limited, but indicate that nicotine can promote a transcriptionally permissive chromatin environment by increasing acetylation of histone H3 and H4. To further explore nicotine-induced histone modifications, we measured histone methyltransferase (HMT) mRNA expression as well as total and promoter-specific H3K9me2 levels. Following administration of nicotine, HMT mRNA and H3K9me2 levels were examined in mouse primary cortical neuronal culture and cortex extracted from mice injected intraperitoneally, as well as in human lymphocyte culture. Furthermore, Bdnf/BDNF mRNA levels were examined as an epigenetically regulated read-out of gene expression. There was a significant decrease of the HMT GLP, G9a and Setdb1 mRNA expression in the nicotine-treated tissue examined, with significant decreases seen in both total and promoter-specific H3K9me2 levels. Increasing doses of nicotine resulted in significant decreases in Bdnf/BDNF promoter specific H3K9me2 binding, leading to enhanced Bdnf/BDNF transcription. Taken together, our data suggest that nicotine reduces markers of a restrictive epigenomic state, thereby leading to a more permissive epigenomic environment.

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