Altered Brain Extracellular Matrix Structure and Sex-Specific Learning/Memory Dysfunction in Mice Lacking the...

Area of Science:

• Neuroscience
• Biochemistry
• Extracellular Matrix Biology

Background:

• Cystatin-related epididymal spermatogenic (CRES) is an epididymal protein involved in ECM formation and host defense.
• CRES and its amyloid forms are present in the mammalian brain ECM.
• The ECM plays crucial roles in brain structure and function.

Purpose of the Study:

• To investigate the role of CRES in brain ECM structure and function.
• To determine the impact of CRES absence on learning, memory, and executive functions.
• To explore potential sex-specific effects of CRES on brain physiology.

Main Methods:

• Utilized a CRES knockout (KO) mouse model.
• Analyzed hippocampal and cortical ECM structure, including loose/interstitial and perineuronal net (PNN) components.
• Assessed behavioral performance in learning, memory, and executive function tasks in young and older CRES KO mice compared to wild-type (WT) controls.

Main Results:

• CRES KO mice exhibited sex-specific structural alterations in brain ECM.
• Young CRES KO males showed deficits in learning, memory, and executive functions compared to WT controls.
• Older CRES KO males did not display behavioral deficits, correlating with normalized PNN ECM structure.

Conclusions:

• CRES is a regulatory or structural component of the brain ECM.
• CRES influences the sex-specific organization and plasticity of the brain ECM.
• CRES impacts sex-specific behaviors related to learning and memory.