Work

Targeting CA2 Perineuronal Nets Restores Recognition Memory and Theta Oscillations in Aged Mice

Year: 2025

Type: article

Abstract: Remembering familiar versus novel stimuli is fundamental to survival, but it is compromised in several neurodegenerative disorders where aging is a key factor. Although the components of the extracellular matrix (ECM) have been suggested to be implicated in memory maintenance, the mechanistic and behavioral roles of ECM during the aging process remain unclear. Here, we employed an accelerated mouse model of aging to elucidate the causal link between ECM dynamics and recognition memory during aging. Aged mice exhibited impaired social and non-social recognition memory, accompanied by increased intensity of perineuronal nets (PNNs), specialized ECM structures in the hippocampal dorsal CA2 (dCA2). A reduction in the power of theta oscillations (3-7 Hz) in the dCA2 of aged mice was also observed. Notably, selective degradation of PNNs in the dCA2 using chondroitinase ABC (ChABC) rescued recognition memory deficits and restored theta oscillations. Together, our findings identify abnormal PNN in the CA2 as a critical factor for age-related deficits in hippocampal-dependent recognition memory and network rhythmicity. These insights raise the possibility that targeting CA2 PNNs could facilitate the development of diagnostic and therapeutic strategies to address age-associated cognitive frailty.

Source: Aging Cell

DOI: 10.1111/acel.70139

Authors: Sonam Fathima Mehak, Apoorva Bettagere Shivakumar, Feyba Jijimon, Amritanshu Gupta, Vikram Gopalakrishna Pillai, Gireesh Gangadharan

Institutions: Manipal Academy of Higher Education, University of Kansas Medical Center

Language: English

Topic: Memory and Neural Mechanisms

Subfield: Cognitive Neuroscience

Field: Neuroscience

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,790