Localization of PPAR isotypes in the adult mouse and human brain.
Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain.
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, United States.|The Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, United States.
Anna
A
Warden
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, United States.
Jay
J
Truitt
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, United States.
Morgan
M
Merriman
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, United States.
Olga
O
Ponomareva
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, United States.
Kelly
K
Jameson
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, United States.|The Institute for Neuroscience, The University of Texas at Austin, Austin, TX 78712, United States.
Laura B
LB
Ferguson
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, United States.
R Dayne
RD
Mayfield
Waggoner Center for Alcohol and Addiction Research, The University of Texas at Austin, Austin, TX 78712, United States.
R Adron
RA
Harris
D000679:Amygdala / Q000187:drug effects; D000818:Animals; D002450:Cell Communication / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007132:Immunoglobulin Isotypes; D051379:Mice; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists / Q000145:classification / Q000235:genetics*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000473:pathology; D020033:Protein Isoforms / Q000145:classification / Q000235:genetics*; D012333:RNA, Messenger / Q000187:drug effects
D007132:Immunoglobulin Isotypes; D047492:Peroxisome Proliferator-Activated Receptors; D020033:Protein Isoforms; D012333:RNA, Messenger