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

Abstract

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). The ex vivo methodology 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.

Chronic exposure to air pollution implications on COVID-19 severity

“…This interplay is aimed to protect the body from immune system dysregulation and minimize tissue damage from associative systemic inflammation [7] , [8] , [10] , [11] . Chronic activation of the HPA axis affects the release of glucocorticoids and contributes to immune dysfunction as immune response is signified by glucocorticoid release [7] , [12] , [13] , [14] , [15] .…”

Chronic Stress Exposure Reduces Parvalbumin Expression in the Rat Hippocampus through an Imbalance of Redox Mechanisms: Restorative Effect of the Antipsychotic Lurasidone

“…We have previously shown that CMS is able to induce depressive-like behaviors such as anhedonia (Rossetti et al, 2016) as well as cognitive impairment (Calabrese et al, 2017), which are associated with alterations in key molecular players for psychiatric disorders (Luoni et al, 2014; Calabrese et al, 2016b; Molteni et al, 2016). We also investigated the effect of a chronic treatment with lurasidone in counteracting the CMS-induced alterations in rat hippocampus.…”

The potential role of exercise in chronic stress-related changes in AMPA receptor phenotype underlying synaptic plasticity

“…Glutamatergic synapses that lack AMPAR current― known as “silent synapses”―are not able to achieve sufficient depolarization (excitation) despite containing functional N-methyl-D-aspartate (NMDA) receptors 27 . In addition to NMDA receptor-dependent Ca2+ influx, AMPAR-dependent synaptic Ca2+ influx is required for NMDA receptor-mediated LTP 14 - 15 , 28 . Additionally, enhanced LTP expression has been observed in mice with genetic deletion of GluR2 29 , 30 .…”

“…Chronic stress-induced abnormalities in synaptic plasticity are modulated by corticosterone, neurotrophins, oxidative stress, and various neurotransmitters 8 , 11 , 12 , 13 . For example, chronic mild stress has been shown to reduce hippocampal transcription of hippocampal brain-derived natriuretic factor (BDNF), which reached basal levels in an isoform-specific manner by KCl-treated depolarization, suggesting that neurotrophins differentially regulate activity-dependent transcription of BDNF 14 .…”

“…In particular, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPAR) is a fast ligand-gated cation channel. AMPAR-dependent synaptic influx of cations, especially Ca2+, plays a critical role in synaptic plasticity 14 - 16 . Diverse chronic stress leads to abnormal synaptic function of AMPAR, including AMPAR-mediated excitation in the synapse 17 - 19 .…”