Dataset Information

A Minimal Transcriptional Footprint of Endogenous Cholinergic Signaling in the Hippocampus After Acute and Repeated Forced Swim Stress

ABSTRACT: The septohippocampal cholinergic system has long been implicated in memory and plasticity, yet the scope and mechanisms of its endogenous transcriptional control remain unclear, largely due to reliance on pharmacological agonist studies that produce broad, non-physiological activation. Using acute forced swim stress (FSS) as an ethological trigger of endogenous acetylcholine release, we dissected cholinergic regulation of hippocampal immediate-early genes (IEGs) across transcriptional and translational levels. Systemic muscarinic blockade by scopolamine identified a remarkably selective cohort of cholinergic-dependent IEGs—Npas4, Arc, and Egr1—whose induction was region-specific along the septotemporal axis and profoundly reshaped by stress history. However, chronic immunotoxic lesion of septohippocampal cholinergic inputs completely failed to recapitulate these transcriptional effects, leaving stress-evoked IEG mRNA induction fully intact. This divergence unveiled a cryptic post-transcriptional cholinergic function: although Egr1 mRNA was robustly induced by FSS in lesioned animals, Egr1 protein synthesis was entirely abolished. Thus, septohippocampal acetylcholine does not act as a broad permissive signal for neuronal activation, but rather as a dual-tiered regulator—selectively gating transcription of a core plasticity module while uniquely licensing Egr1 translation. These findings reframe cholinergic signaling from a global transcriptional driver to a context-dependent molecular switch, reconciling prior contradictions and implicating translational dysregulation as a mechanism in cholinergic dysfunction.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE346582 | GEO | 2026/09/16

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Tissue Factor Pathway Inhibitor-2 is Induced by Fluid Shear Stress in Vascular Smooth Muscle Cells and Affects Cell Proliferation and Survival Introduction: Vascular smooth muscle cells (SMCs) are exposed to fluid shear stress (FSS) after interventional procedures such as balloon-angioplasty. Whereas the effects of hemodynamic forces on endothelial cells are explored in detail, the influence of FSS on smooth muscle cell function is poorly characterized. Here, we investigated the effect of FSS on SMC gene expression and function. Methods: Laminar FSS of arterial level (14 dynes/cm2) was applied to SMC cultures for 24 h in a parallel-plate flow chamber. The effect of FSS on gene expression was first screened with microarray technology and the results further verified by real time (RT) PCR and immunoblotting. Protein expression was also studied in the rat carotid artery after balloon-injury and DNA synthesis and apoptosis was examined in SMCs in vitro. Results: Microarrays identified tissue-pathway inhibitor-2 (TFPI-2) as the most differentially expressed gene by FSS in cultured SMCs. The regulatory effect of FSS on the expression of TFPI-2 was confirmed by RT-PCR and immunobloting demonstrating a more than 400-fold increase in TFPI-2 expression in SMCs exposed to FSS compared to static controls and a consistent upregulation at the protein level. Functionally, SMC proliferation was decreased by FSS and recombinant TFPI-2 was found to inhibit SMC proliferation and induce SMC apoptosis as indicated by activation of caspase-3. In vivo, TFPI-2 expression was found to be up-regulated 5, 10 and 20 h after rat carotid balloon-injury and immunohistochemistry demonstrated TFPI-2 protein in luminal SMCs exposed to FSS in rat carotid intimal hyperplasia 10 days after balloon-injury. Conclusion: FSS strongly influence gene expression in cultured SMCs and induce TFPI-2 expression, which is also expressed after rat carotid balloon injury in luminal SMCs exposed to FSS. Functionally, TFPI-2 may play an important role in vessel wall repair by regulating SMC proliferation and survival. Further studies are needed to elucidate the mechanisms by which TFPI-2 control SMC function. 3 x 2 samples from a paired fluid shear stress experiment on smooth muscle cells.

Dataset Information

A Minimal Transcriptional Footprint of Endogenous Cholinergic Signaling in the Hippocampus After Acute and Repeated Forced Swim Stress

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets