p53 deficiency increases vulnerability to chronic stress-induced anxiety- and depression-like behaviors: Role of calcium dysregulation and BDNF signaling.

Authors

Hyun Soon Choi, Seong Hee Jeon, Hanyang Liu, Minji Kim, Jun Sang Yu, Seung Sik Yoo, Dong Ju Son, Sang-Bae Han, In Jun Yeo, Sung Cil Lim, Jin Tae Hong

Published in

Behavioural brain research. Pages 116437. Aug 15, 2026. Epub Aug 15, 2026.

Abstract

The tumor suppressor protein p53 is a known modulator of neurodegenerative disease (ND) processes. Although p53 expression is increased in the brains of patients with Alzheimer's disease, Parkinson's disease, and ischemic stroke, its role in mood disorders such as anxiety and depression remains unclear. To investigate the role of p53 in behavioral responses to chronic stress, we examined behavioral and molecular alterations in p53 knockout (p53^-/-) mice and wild type mice. In p53^-/- mice, increased vulnerability to chronic unpredictable mild stress (CUMS)-induced anxiety- and depression-like behaviors was observed following CUMS exposure. In parallel with these behavioral changes, BDNF expression was reduced, whereas glutamate levels were elevated in the prefrontal cortex of p53^-/- mice. Increased calcium-associated staining and NMDAR2B expression were observed together with increased neuronal injury- and cell death-related markers. In primary cortical neurons derived from p53^-/- mice, corticosterone treatment resulted in greater increases in glutamate levels, NMDAR2B expression compared to wild-type controls. Cell death markers (cleaved caspase-3, p-p38, p-JNK) were upregulated, while neuroprotective signals (BDNF, p-Akt, p-ERK, p-CREB) were suppressed in p53^-/- mice, and corticosterone-treated primary neuronal cells from p53^-/- mice. These findings indicate that p53 deficiency is associated with enhanced vulnerability to CUMS-induced anxiety- and depression-like behaviors and is accompanied by alterations in calcium handling, glutamate homeostasis, neuronal injury-related markers, and BDNF-associated neuroprotective signaling.

PMID:
42603633
Bibliographic data and abstract were imported from PubMed on 16 Aug 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.