| First Author | Moosecker S | Year | 2021 |
| Journal | Neuroscience | Volume | 479 |
| Pages | 91-106 | PubMed ID | 34762981 |
| Mgi Jnum | J:329524 | Mgi Id | MGI:6854641 |
| Doi | 10.1016/j.neuroscience.2021.10.029 | Citation | Moosecker S, et al. (2021) Brain Expression, Physiological Regulation and Role in Motivation and Associative Learning of Peroxisome Proliferator-activated Receptor gamma. Neuroscience 479:91-106 |
| abstractText | Like other members of the superfamily of nuclear receptors, the peroxisome proliferator-activated receptor gamma (PPARgamma), is a ligand-activated transcription factor known for its insulin-sensitizing actions in the periphery. Despite only sparse evidence for PPARgamma in the CNS, many reports suggest direct PPARgamma-mediated actions in the brain. This study aimed to (i) map PPARgamma expression in rodent brain areas, involved in the regulation of cognitive, motivational, and emotional functions, (ii) examine the regulation of central PPARgamma by physiological variables (age, sex, obesity); (iii) chemotypically identify PPARgamma-expressing cells in the frontal cortex (FC) and hippocampus (HP); (iv) study whether activation of PPARgamma by pioglitazone (Pio) in FC and HP cells can induce target gene expression; and (v) demonstrate the impact of activated PPARgamma on learning behavior and motivation. Immunoreactive PPARgamma was detectable in specific sub-nuclei/subfields of the FC, HP, nucleus accumbens, amygdala, hypothalamus, thalamus, and granular layers of the cerebellum. PPARgamma protein levels were upregulated during aging and in high fat diet-induced obesity. PPARgamma mRNA expression was upregulated in the amygdala of females (but not males) that were made obese. Neural precursor cells, mature neurons, and astrocytes in primary FC and HP cultures were shown to express PPARgamma. Pioglitazone dose-dependently upregulated PPARgamma target genes in manner that was specific to the origin (FC or HP) of the cultures. Lastly, administration of Pio impaired motivation and associative learning. Collectively, we provide evidence for the presence of regulatable PPARgamma in the brain and demonstrate their participation the regulation of key behaviors. |
