Dataset Information

Deficiency of the palmitoyl acyltransferase ZDHHC7 modulates gene expression in mice after a mild chronic stress paradigm

ABSTRACT: Chronic stress (CS) is a debilitating condition that negatively affects body and brain. In mice, CS effects range from changes in behaviour down to the level of gene expression. These effects are partly mediated by sex and sex steroid hormones, which in turn are affected by the palmitoyl acyltransferase ZDHHC7. ZDHHC7 might modulate also the response to CS via palmitoylation of sex steroid hormone receptors and other proteins critical for neuronal structure and functions. Therefore, we aimed to investigate the role of ZDHHC7 in response to CS on different system levels in a mouse model of Zdhhc7-deficiency. Female and male Zdhhc7-knockout (KO) and -wildtype (WT) mice underwent a four-week-mild CS paradigm or non-stress control (C) condition. After C or CS, amongst other analyses, brain gene expression profiles (via mRNA-seq transcriptomics) were investigated. Analyses focused on effects of genotype (KO vs. WT) or condition (C vs. CS) separately in both sexes. Our results revealed significant effects particularly in females. Female KOs showed upregulated cortistatin expression after CS (C vs. CS: p<0.05). Zdhhc7-deficiency seemed to be related to a sex-specific stress response and may reveal genetic factors of CS-resilience in female mice.

ORGANISM(S): Mus musculus

PROVIDER: GSE281404 | GEO | 2025/01/24

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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.

Dataset Information

Deficiency of the palmitoyl acyltransferase ZDHHC7 modulates gene expression in mice after a mild chronic stress paradigm

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets