Pparrxr Heterodimers in the Brain

Using the RNase protection assay, we have shown that the mRNAs encoding PPARa, RXRa, PPARP, and RXRP are readily detectable in primary cultures of both cortical astrocytes and meningeal fibroblasts.16 Such data predict the presence of up to four PPAR:RXR heterodimers in such cells, namely PPARa:RXRa, PPARa:RXRp, PPARP:RXRa, and PPARP:RXRP. The predicted presence of PPARa:RXRa and PPARa:RXR.p favours the notion that fatty acid-induced activation of mHS gene expression by incoming fatty acids occurs (in an analogous fashion to that observed in liver hepatocytes) in cortical astrocytes and meningeal fibroblasts, given that such activation may, in part, be repressed by the effects of PPARP :RXRa . The action of PPARP :RXRP on gene expression is, as yet, undefined. In summary, there is evidence to suggest that both cortical astrocytes and meningeal fibroblasts may have the ability in vivo to access and rapidly utilise (via PPAR:RXR-mediated activation of enzymes of P-oxidation and ketogenesis) fatty acid supplies derived from the circulatory system. Metabolic hormones such as insulin and glucocorticoids are involved in the regulation of PPAR, RXR and mHS gene expression and, with this in mind, we now turn to the potential involvement of such hormones in long-term upregulation of neural ketogenic systems.

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