Activation of brain‐derived neurotrophic factor signaling in the basal forebrain reverses acute sleep deprivation‐induced fear memory impairments

Abstract

Introduction:The mechanisms underlying sleep deprivation-induced memory impairments and relevant compensatory signaling pathways remain elusive. We tested the hypothesis that increased brain-derived neurotrophic factor (BDNF) expression in the basal forebrain following acute sleep deprivation was a compensatory mechanism to maintain fear memory performance. Methods: Adult male Wistar rats were deprived of 6-hr total sleep from the beginning of the light cycle. The effects of sleep deprivation on BDNF protein expression and activation of downstream tropomyosin receptor kinase B (TrkB)/phospholipase C-γ1 (PLCγ1) signaling in the basal forebrain and fear memory consolidation were examined. BDNF or selective downstream TrkB receptor antagonist ANA-12 was further injected into the basal forebrain bilaterally to observe the changes in fear memory consolidation in response to modulation of the BDNF/TrkB signaling. Results: Six hours of sleep deprivation-induced both short-and long-term fear memory impairments. Increased BDNF protein expression and TrkB and PLCγ1 phosphorylation in the basal forebrain were observed after sleep deprivation. Microinjection of BDNF into the basal forebrain partly reversed fear memory deficits caused by sleep deprivation, which were accompanied by increased BDNF protein levels and TrkB/PLCγ1 activation. After ANA-12 microinjection, sleep deprivation-induced activation of the BDNF/TrkB pathway was inhibited and impairments of fear memory consolidation were further aggravated. Conclusions: Acute sleep deprivation induces compensatory increase of BDNF expression in the basal forebrain. Microinjection of BDNF into the basal forebrain mitigates the fear memory impairments caused by sleep deprivation by activating TrkB/ PLCγ1 signaling.

Investigating the effect of crocin on memory deficits induced by total sleep deprivation (TSD) with respect to the BDNF, TrkB and ERK levels in the hippocampus of male Wistar rats

“…Studies have shown that SD can disrupt memory consolidation via altering the hippocampal expression of genes related to synaptic plasticity and memory such as BDNF (Karabulut et al, 2019). BDNF expression is associated with the sleep debt of rats (Ma et al, 2020). It has been shown that 24 hours of RSD reduces BDNF and TrkB levels in the hippocampus and disrupts spatial memory performance of rats in the Morris water maze apparatus (Mahboubi et al, 2019).…”

Is SARS-CoV-2 a Risk Factor of Bipolar Disorder?—A Narrative Review

“…Rapid eye movement (REM) sleep disturbances can relieve symptoms of depression or cause mania. At the same time, after REM sleep deprivation, there is a sudden and short elevation in the BDNF level [ 129 , 130 , 151 , 152 , 153 ].…”

Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner

“…This suggests a need for more intricately designed studies, whereby brain regions of interest are temporarily deactivated during a selected memory maintenance time-frame (e.g., for a 2 week period following CFC, but not during the memory recall period). Another potential experiment that could assess the functional role of these markers in fear maintenance would be to administer ANA-12, an antagonist for the BDNF receptor TrKB (Ma et al, 2020 ). If microinjection of ANA-12 into the pre-limbic cortex altered the maintenance of fear memory, then a functional role for BDNF could be confirmed.…”