Dataset Information

Serpina1e mediates the exercise-induced enhancement of hippocampal memory

ABSTRACT: Although exercise improves cognition, the specific molecules responsible for these beneficial effects remain unclear. Here, we propose that the myokine Serpina1e acts as a molecular mediator for these effects. Using an in vivo myokine-labeling mouse model, we confirmed that the Serpina1 family of proteins are increased after 4 weeks of aerobic exercise. Systemic delivery of recombinant Serpina1e enhanced hippocampal memory formation, promoted hippocampal neurogenesis, and elevated BDNF levels. Moreover, plasma Serpina1e can cross the blood–cerebral spinal fluid (CSF) barrier and blood–brain barrier to reach the brain, thereby influencing hippocampal function. In vivo Serpina1e infusion also induced cognitive enhancement. Our findings suggest that Serpina1e is a myokine that migrates to the hippocampus and mediates exercise-induced memory enhancement by triggering neurotrophic growth signaling. This molecular mechanism underlying the beneficial effects of exercise on cognitive function may have implications for the development of therapeutic interventions for alleviating cognitive disorders.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Blood Plasma

SUBMITTER: Sanghee Shin

LAB HEAD: Jong-Seo Kim

PROVIDER: PXD055604 | Pride | 2026-06-15

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Plasma_Biotin_172_Naq448_J100_2201.raw	Raw
	Plasma_Biotin_1_118_Naq448_J100_2106.raw	Raw
	Plasma_Biotin_245_Naq448_J100_2201.raw	Raw
	Plasma_Biotin_254_Naq448_J100_2201.raw	Raw
	Plasma_Biotin_2_125_Naq448_J100_2106.raw	Raw

Items per page:

1 - 5 of 24

Publications

Serpina1e mediates the exercise-induced enhancement of hippocampal memory in male mice.

Kim Hyunyoung H Shin Sanghee S Han Jeongho J Yun Kangseok K Kim Jong-Seo JS Park Hyungju H

Nature communications 20260409 1

Exercise enhances learning and memory, not only through improved cardiometabolic but also through body-brain interactions mediated by secreted factors. Given the prominent role of skeletal muscle during exercise, muscle-derived factors, myokines, are believed to mediate the exercise-induced cognitive enhancements. Here, we demonstrate that intramuscular Serpina1e is upregulated following exercise in male mice. Systemic delivery of recombinant Serpina1e or intramuscular overexpression of Serpina1 ...[more]

PMID: 41957371

Similar Datasets

Project description:We utilized an unbiased RNA-sequencing approach to uncover genes in the dorsal hippocampus that are differentially expressed under conditions where exercise benefits are maintained throughout sedentary delay periods and enable the formation of long-term memory and synaptic plasticity. Engagement in different exercise parameters resulted in a diverse transcriptional profile as defined by differences in the number, pattern, and type of genes up and down-regulated. To identify genes that play a critical role in cognitive enhancement, we next focused our attention on exercise groups that enable robust long-term memory formation under inadequate subthreshold acquisition sessions of the hippocampus-dependent object location memory task. By intersecting up regulated genes when exercise facilitated learning, we identify potential regulators of learning and targets for memory enhancement. We identify a gene coding for a type 1 membrane receptor and kinase for the TGF-β family of signaling molecules, Acvr1c as one of few genes showing upregulation in conditions where exercise enabled the formation of long-term memory, indicating a gate-type role for Acvr1c in memory consolidation. In addition to overall gene expression levels, we identify potential regulators upstream of gene targets within the window for cognitive enhancement. Additionally, we use three complementary analyses to examine the mechanisms responsible for maintaining the ‘molecular memory window’ for exercise utilizing up regulated differentially expressed genes compared to sedentary controls. These analyses include: gene coexpression network analysis to identify potential hub genes for each exercise condition, predicted pathways altered by exercise, and gene ontology enrichment analysis of cellular components altered by exercise. Together, results identify Acvr1c as one of few genes up regulated only under conditions where exercise enabled the formation of long-term memory and synaptic plasticity, suggesting a role for Acvr1c in facilitation of memory consolidation. Follow up experiments manipulating ACVR1C function, find that it serves as an essential bidirectional regulator of long-term memory formation capable of alleviating impairments in hippocampus-dependent memory and synaptic plasticity associated with age and Alzheimer’s Disease.

Project description:Thiazolidinediones (TZDs) are agonists at peroxisome proliferator-activated gamma-type (PPAR-y) receptors and are used clinically for the treatment of type 2 diabetes where they have been shown to reestablish insulin sensitivity, improve lipids profile, and reduce inflammation. Recent work also suggests that TZDs may be beneficial in Alzheimer's disease (AD), ameliorating cognitive decline early in the disease process. However, there have been only a few studies identifying mechanisms through which cognitive benefits may be exerted. Starting at 10 months of age, the triple transgenic mouse model of AD (3xTg-AD) with accelerated amyloid-B (AB) deposition and tau pathology was treated with the TZD pioglitazone (PIO- Actos) at 18 mg/Kg body weight/day. After four months, PIO-treated animals showed multiple beneficial effects, including improved learning on the active avoidance task, reduced serum cholesterol, decreased hippocampal AB deposits, and enhanced short- and long-term plasticity. Baseline electrophysiological membrane properties and blood glucose levels were unchanged by PIO treatment. Gene microarray analyses of hippocampal tissue identified predicted transcriptional responses following TZD treatment as well as potentially novel targets of TZDs, including facilitation of estrogenic processes, and decreases in glutamatergic and ketone metabolic/ cholesterol dependent processes. Taken together, these results confirm prior animal studies showing that TZDs can ameliorate cognitive deficits associated with AD-related pathology, but also extend these findings by pointing to novel molecular targets in the brain. Keywords : Hippocampus; LTP; Microarray analysis; Avoidance learning; Aging; PPAR; Synaptic hyperpolarization; T2DM We used the 3xTg-AD mouse model of Alzheimer's disease and monitored the effects of pioglitazone (PIO-Actos a TZD) on behavioral, electrophysiological, and molecular variables. Emphasis was placed on identifying hippocampal PIO-sensitive genes that were also associated with learning and memory processes. Starting at 10 months of age, female mice were treated for approximately 14 weeks with either a control diet or a PIO-containing diet. PIO was incorporated into the diet to yield a final dose of approximately 18 mg/kg body weight/day.