Altered Brain Extracellular Matrix Structure and Sex-Specific Learning/Memory Dysfunction in Mice Lacking the Functional Amyloid Cystatin-Related Epididymal Spermatogenic (CRES)
- 1Texas Tech University Health Sciences Center
Abstract
Cystatin-related epididymal spermatogenic (CRES) is a member of a reproductive subgroup of family 2 cystatins and part of a functional amyloid-containing extracellular matrix (ECM) with host defense functions in the epididymal lumen. CRES and the endogenous epididymal amyloid matrix exhibit high plasticity, forming distinct amyloid structures, with antimicrobial functions tailored to specific bacterial strains. We recently demonstrated that CRES/CRES amyloid is also present in the mammalian brain ECM. In this study, we utilized a CRES knockout (KO) mouse model to determine if the loss of CRES altered the structure of the hippocampal and cortical ECM and impacted brain function. We report that CRES KO male and female mice exhibited sex-specific structural changes in both the loose/interstitial and perineuronal net (PNN) ECM. Additionally, young CRES KO males but not females displayed deficits in learning, memory and executive functioning when compared to WT controls. In contrast, older CRES KO males did not exhibit behavioral deficits, a finding that correlated with the observation of a similar PNN ECM structure when compared to WT mice. Our data suggest that CRES functions as a regulatory or structural component of the brain ECM, contributing to its sex-specific structural organization and plasticity, affecting sex-specific behaviors of learning and memory.
Related
- Altered Brain Extracellular Matrix Structure and Sex-Specific Learning/Memory Dysfunction in Mice Lacking the Functional Amyloid Cystatin-Related Epididymal Spermatogenic
- S-adenosylmethionine ameliorates spermatogenic dysfunction and sperm DNA damage via transsulfuration pathway
- Structure of Caspase9 gene in Qianhua Mutton Merino and its association with spermatogenic function analysis
- Aluminum-induced epididymal damage and infertility in adult male rats: A nanotechnology-based perspective on nanoscale toxicity and oxidative mechanisms
- Amyloid/RNA Condensates with Germ Granule Characteristics Are Present in Rat Epididymal Spermatozoa and Exhibit Prion-Like Propagation Activity
BibTeX
@misc{gomez2026altered,
title = {{Altered Brain Extracellular Matrix Structure and Sex-Specific Learning/Memory Dysfunction in Mice Lacking the Functional Amyloid Cystatin-Related Epididymal Spermatogenic (CRES)}},
author = {A. Gomez and A. F. Logsdon and J. D. Bailoo and G. A. Cornwall},
howpublished = {bioRxiv},
year = {2026},
month = may,
doi = {10.64898/2026.05.27.728219},
url = {https://www.biorxiv.org/content/10.64898/2026.05.27.728219v2},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Altered Brain Extracellular Matrix Structure and Sex-Specific Learning/Memory Dysfunction in Mice Lacking the Functional Amyloid Cystatin-Related Epididymal Spermatogenic (CRES)
AU - A. Gomez
AU - A. F. Logsdon
AU - J. D. Bailoo
AU - G. A. Cornwall
PY - 2026
DA - 2026/05/27
PB - bioRxiv
DO - 10.64898/2026.05.27.728219
UR - https://www.biorxiv.org/content/10.64898/2026.05.27.728219v2
AB - Cystatin-related epididymal spermatogenic (CRES) is a member of a reproductive subgroup of family 2 cystatins and part of a functional amyloid-containing extracellular matrix (ECM) with host defense functions in the epididymal lumen. CRES and the endogenous epididymal amyloid matrix exhibit high plasticity, forming distinct amyloid structures, with antimicrobial functions tailored to specific bacterial strains. We recently demonstrated that CRES/CRES amyloid is also present in the mammalian brain ECM. In this study, we utilized a CRES knockout (KO) mouse model to determine if the loss of CRES altered the structure of the hippocampal and cortical ECM and impacted brain function. We report that CRES KO male and female mice exhibited sex-specific structural changes in both the loose/interstitial and perineuronal net (PNN) ECM. Additionally, young CRES KO males but not females displayed deficits in learning, memory and executive functioning when compared to WT controls. In contrast, older CRES KO males did not exhibit behavioral deficits, a finding that correlated with the observation of a similar PNN ECM structure when compared to WT mice. Our data suggest that CRES functions as a regulatory or structural component of the brain ECM, contributing to its sex-specific structural organization and plasticity, affecting sex-specific behaviors of learning and memory.
ER -