Mice Lacking the Transcriptional Coactivator PGC-1α Exhibit Hyperactivity

Jia Wang, Qi Yun, Jin Jun Qian, Hua Rong Song, Lei Wang, Samuel Eguasi Inkabi, Ru Jing Xu, Yan Mei Hu, Wei Ning Zhang, Haim Einat

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Significant evidence from various sources suggests that structural alterations in mitochondrial function may play a role in both the pathogenesis of mood disorders and the therapeutic effects of available treatments. PGC-1α is a distinct transcriptional regulator designed to mediate the synchronous release of neurotransmitter in the brain and thereby to coordinate a number of gene expression pathways to promote mitochondrial biogenesis and oxidative phosphorylation. The role of PGC-1α in the context of affective disorder phenotypes and treatments has been suggested but not studied in depth. To further investigate the possible involvement of PGC-1α in affective disorders, we generated conditional PGC-1α null mice through transgenic expression of cre recombinase under the control of a Dlx5/6 promoter; cre-mediated excision events were limited to γ-amino-butyric-acid (GABA)-ergic specific neurons. We tested these mice in a battery of behavioral tests related to affective change including spontaneous activity, elevated plus maze, forced swim test, and tail suspension test. Results demonstrated that mice lacking PGC-1α in GABAergic neurons exhibited increased activity across tests that might be related to a mania-like phenotype. These results suggest possible relevance of PGC-1α to affective change, which corresponds with data connecting mitochondrial function and affective disorders and their treatment.

Original languageEnglish
Pages (from-to)182-188
Number of pages7
JournalNeuropsychobiology
Volume78
Issue number4
DOIs
StatePublished - 1 Nov 2019
Externally publishedYes

Keywords

  • Animal model
  • Bipolar disorder
  • Mania
  • Mitochondria

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Psychiatry and Mental health
  • Biological Psychiatry

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