Dataset Information

Abnormal expression of cortical cell cycle regulators underlying anxiety and depressive-like behavior in mice exposed to chronic stress.

ABSTRACT:

Background

The cell cycle is a critical mechanism for proper cellular growth, development and viability. The p16^INK4a and p21^Waf1/Cip1 are important regulators of the cell cycle progression in response to internal and external stimuli (e.g., stress). Accumulating evidence indicates that the prefrontal cortex (PFC) is particularly vulnerable to stress, where stress induces, among others, molecular and morphological alterations, reflecting behavioral changes. Here, we investigated if the p16^INK4a and p21^Waf1/Cip1 expression are associated with behavioral outcomes.

Methods

Prefrontal cortex mRNA and protein levels of p16^INK4A and p21^Waf1/Cip1 of mice (six independent groups of C57BL/6J, eight mice/group, 50% female) exposed from 0 to 35 days of chronic restraint stress (CRS) were quantified by qPCR and Western Blot, respectively. Correlation analyses were used to investigate the associations between cyclin-dependent kinase inhibitors (CKIs) expression and anxiety- and depression-like behaviors.

Results

Our results showed that the PFC activated the cell cycle regulation pathways mediated by both CKIs p16^INK4A and p21^Waf1/Cip1 in mice exposed to CRS, with overall decreased mRNA expression and increased protein expression. Moreover, correlation analysis revealed that mRNA and protein levels are statistically significant correlated with anxiety and depressive-like behavior showing a greater effect in males than females.

Conclusion

Our present study extends the existing literature providing evidence that PFC cells respond to chronic stress exposure by overexpressing CKIs. Furthermore, our findings indicated that abnormal expression of p16^INK4A and p21^Waf1/Cip1 may significantly contribute to non-adaptive behavioral responses.

SUBMITTER: Mendes-Silva AP

PROVIDER: S-EPMC9772437 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Abnormal expression of cortical cell cycle regulators underlying anxiety and depressive-like behavior in mice exposed to chronic stress.

Mendes-Silva Ana Paula AP Prevot Thomas Damien TD Banasr Mounira M Sibille Etienne E Diniz Breno Satler BS

Frontiers in cellular neuroscience 20221208

<h4>Background</h4>The cell cycle is a critical mechanism for proper cellular growth, development and viability. The p16<sup>INK4a</sup> and p21<sup>Waf1/Cip1</sup> are important regulators of the cell cycle progression in response to internal and external stimuli (e.g., stress). Accumulating evidence indicates that the prefrontal cortex (PFC) is particularly vulnerable to stress, where stress induces, among others, molecular and morphological alterations, reflecting behavioral changes. Here, we ...[more]

PMID: 36568887

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Dataset Information

Abnormal expression of cortical cell cycle regulators underlying anxiety and depressive-like behavior in mice exposed to chronic stress.

Background

Methods

Results

Conclusion

Publications

Abnormal expression of cortical cell cycle regulators underlying anxiety and depressive-like behavior in mice exposed to chronic stress.

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