Peroxisome Proliferator-Activated Receptor beta/delta in the Brain: Facts and Hypothesis

Abstract

peroxisome proliferator-activated receptors (PPARs) are nuclear receptors acting as lipid sensors. Besides its metabolic activity in peripheral organs, the PPAR beta/delta isotype is highly expressed in the brain and its deletion in mice induces a brain developmental defect. Nevertheless, exploration of PPARbeta action in the central nervous system remains sketchy. The lipid content alteration observed in PPARbeta null brains and the positive action of PPARbeta agonists on oligodendrocyte differentiation, a process characterized by lipid accumulation, suggest that PPARbeta acts on the fatty acids and/or cholesterol metabolisms in the brain. PPARbeta could also regulate central inflammation and antioxidant mechanisms in the damaged brain. Even if not fully understood, the neuroprotective effect of PPARbeta agonists highlights their potential benefit to treat various acute or chronic neurological disorders. In this perspective, we need to better understand the basic function of PPARbeta in the brain. This review proposes different leads for future researches.

Figure 1

Expression of PPARβ in the adult mouse brain. Quantitative and spatial expression of PPARβ in the mouse brain: (a) Quantitative RT-PCR data, (b) Brain sagittal section. Moderated expression levels are in red and weak expression in blue. OA: olfactory areas, Cx: cerebral cortex, CP: caudate putamen, Hi: hippocampus, Th: thalamus, Hy: hypothalamus, Arc: arcuate nucleus, Co: colliculus, BS: brain stem, Cb: cerebellum. (MousePat: http://www-mci.u-strasbg.fr/mousepat/-consulted 8-08-2008).

Figure 2

PPARβ potential role in neural cell differentiation during development. PPARβ is expressed in the embryo and in the differentiating cells of the CNS and plays important role for the maintenance and/or differentiation of neural stem cells (NSC). PPARβ maintains NSC in an undifferentiated proliferative status [45]. Once the NSC cells have started to differentiate, PPARβ could play a role in (1) neuronal differentiation, inducing the morphological characteristics and the gene expression patterns of neuronal cells, (2) promoting the oligodendrocyte precursor cells (OPC) differentiation [46], strongly expressing PPARβ [47], to mature oligodendrocytes [7]. In promoting differentiation, PPARβ also influences cell cycle and proliferation rate. Up to today no role has been clearly established for PPARβ in astrocyte differentiation. (↑ Activation in red, ⊥ Repression in blue).