Dataset Information

Molecular mechanism of resilience in stress-related disorders

ABSTRACT: Stress resilience is a dynamic process whereby an individual can withstand stressful events while still maintaining normal, physiological functioning. Resilience is inferred from an observed level of cognitive performance higher than expected in the face of a demonstrated stressful event. The neural rewiring that leads to stress resilience resides in structural and functional synaptic plasticity. The importance of studying stress resilience has become more evident in the last years, considering the frequency and variety of stressors that humans have to cope with and the attendant stress-related disorders, and especially now more than ever due to the COVID-19 worldwide crisis. The molecular basis for stress resilience and the factors that modulate it are important research areas in neuropsychiatry and contemporary neuroscience.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Monika Zareba-Koziol

LAB HEAD: Jakub Wlodarczyk

PROVIDER: PXD026590 | Pride | 2025-05-06

REPOSITORIES: Pride

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Publications

Stress resilience is an active and multifactorial process manifested by structural, functional, and molecular changes in synapses.

Bączyńska E E Zaręba-Kozioł M M Ruszczycki B B Krzystyniak A A Wójtowicz T T Bijata K K Pochwat B B Magnowska M M Roszkowska M M Figiel I I Masternak J J Pytyś A A Dzwonek J J Worch R R Olszyński K H KH Wardak A D AD Szymczak P P Labus J J Radwańska K K Jahołkowski P P Hogendorf A A Ponimaskin E E Filipkowski R K RK Szewczyk B B Bijata M M Włodarczyk J J

Neurobiology of stress 20241022

Stress resilience is the ability of neuronal networks to maintain their function despite the stress exposure. Using a mouse model we investigate stress resilience phenomenon. To assess the resilient and anhedonic behavioral phenotypes developed after the induction of chronic unpredictable stress, we quantitatively characterized the structural and functional plasticity of excitatory synapses in the hippocampus using a combination of proteomic, electrophysiological, and imaging methods. Our result ...[more]

PMID: 39524934

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Project description:Although sex differences in the brain are prevalent, the knowledge about mechanisms underlying sex-related effects on normal and pathological brain functioning is rather poor. It is known that female and male brains differ in size and connectivity. Moreover, those differences are related to neuronal morphology and activity, synapse molecular organization, synaptic plasticity, and molecular signalling pathways. Among different processes assuring proper synapse function are posttranslational modifications, and among them, S-palmitoylation emerges as a crucial mechanism underlying synaptic integrity. Protein S-palmitoylation (S-PALM) refers to the covalent attachment of palmitic acid (C16:0) to cysteine residue(s) via the formation of a thioester bond. Protein S-PALM is governed by a family of PATs, also known as DHHC proteins. Here we focused on the sex-related functional importance of DHHC7 acyltransferase. Under physiological conditions, DHHC7 emerges of particular interest because it palmitoylates various synaptic proteins involved in the regulation of cellular polarity and proliferation as well as in stress and anxiety-related pathology. Moreover, DHHC7 is responsible for S-PALM of sex steroid receptors. Functionally, S-PALM of these receptors regulates their trafficking to the plasma membrane as well as their rapid responses to sex steroid hormones. Using mass spectrometry-based method PANIMoni we identified sex-dependent differences in the S-palmitoylation of synaptic proteins, potentially involved in the regulation of passive membrane properties and excitability (e.g. potassium voltage-gated channels), synaptic transmission (e.g. subunits of glutamate or kainate receptors, voltage-dependent calcium channels) as well as signalling proteins involved in structural plasticity of dendritic spines (e.g. G-proteins and Rab GTPase). Furthermore, to determine a mechanistic source for sex-dependent changes in protein S-palmitoylation we used synaptoneurosomes from DHHC-7 knock-out -/- (DHHC7 KO) female and male mice. Our data showed sex-dependent action of DHHC-7 acyltransferase. Such discovery will facilitate the development of novel and targeted treatments congruous with biological sex.

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