Chemogenetic Neuronal Silencing Decouples C-Jun Activation From Cell Death in the Temporal Cortex

Authors

Caleb A Wood
Preethi Somasundaram
Jacob M Dundee
Melissa A Rudy
Trent A Watkins
Joanna L Jankowsky

Language

English

Publication Date

12-1-2024

Journal

European Journal of Neuroscience

DOI

10.1111/ejn.16575

PMID

39449079

PMCID

PMC12633068

PubMedCentral® Posted Date

11-21-2025

PubMedCentral® Full Text Version

Author MSS

Abstract

Initial symptoms of neurodegenerative diseases are often defined by the loss of the most vulnerable neural populations specific to each disorder. In the early stages of Alzheimer's disease, vulnerable circuits in the temporal lobe exhibit diminished activity prior to overt degeneration. It remains unclear whether these functional changes contribute to regional vulnerability or are simply a consequence of pathology. We previously found that entorhinal neurons in the temporal cortex undergo cell death following transient suppression of electrical activity, suggesting a causal role for activity disruption in neurodegeneration. Here we demonstrate that electrical arrest of this circuit stimulates the injury-response transcription factor c-Jun. Entorhinal silencing induces transcriptional changes consistent with c-Jun activation that share characteristics of gene signatures in other neuronal populations vulnerable to Alzheimer's disease. Despite its established role in the neuronal injury response, inhibiting c-Jun failed to ameliorate entorhinal degeneration following activity disruption. Finally, we present preliminary evidence of integrated stress response activity that may serve as an alternative hypothesis to what drives entorhinal degeneration after silencing. Our data demonstrate that c-Jun is activated in response to neuronal silencing in the entorhinal cortex but is decoupled from subsequent neurodegeneration.

Keywords

Animals, Neurons, Cell Death, Proto-Oncogene Proteins c-jun, Entorhinal Cortex, Mice, Temporal Lobe, Male, Mice, Inbred C57BL, Alzheimer’s disease, selective neuronal vulnerability, entorhinal cortex, c-Jun, chemogenetic silencing, GlyCl

Published Open-Access

yes

Recommended Citation

Wood, Caleb A; Somasundaram, Preethi; Dundee, Jacob M; et al., "Chemogenetic Neuronal Silencing Decouples C-Jun Activation From Cell Death in the Temporal Cortex" (2024). Faculty and Staff Publications. 4927.
https://digitalcommons.library.tmc.edu/baylor_docs/4927