Mice Lacking the Transcriptional Coactivator PGC-1 α Exhibit Hyperactivity

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-1 α 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 di sorder 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-med iated 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 tre atment.Neuropsychobiology

Source: Neuropsychobiology - July 2, 2019 Category: Psychiatry & Psychology Source Type: research