Evidence map›Paper›PMID 40522224›Full record

ArticleAging cell2025

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

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

Abstract read
In one paragraph

Article in Aging cell, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Critical Periods and Beyond: Dynamic Functions of Perineuronal Nets in Cognition, Development, and Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025
    Review
  5. Developmental CA2 perineuronal net reduction restores social memory inbioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Sonam Fathima MehakDepartment of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Apoorva Bettagere ShivakumarDepartment of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Feyba JijimonDepartment of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Amritanshu GuptaDepartment of Biomedical Engineering, Manipal Institute of Technology, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Vikram Gopalakrishna PillaiDepartment of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA.ORCID 0000-0002-5829-7084
Gireesh GangadharanDepartment of Ageing Research, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India.ORCID 0000-0001-9369-319X

Funding

Department of Biotechnology, Ministry of Science and Technology, India BT/RLF/Re-entry/49/2018Science and Engineering Research Board CRG/2020/004205
6 · The paper itself

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.

Indexed as

CA2 Region, HippocampalMemoryNerve NetAgingAnimalsChondroitin ABC LyaseExtracellular MatrixMaleMemory DisordersMiceMice, Inbred C57BLTheta RhythmChondroitin ABC Lyaseagingextracellular matrix (ECM)perineuronal nets (PNN)recognition memorytheta oscillations

Identifiers

PMID40522224
PMCPMC12419842

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.