OBJECTIVE Peroxisome proliferator activated receptor alpha(PPARα)is an important protective factor in neurovascular diseases such as ischemic stroke.Although PPARαexpression is higher in neurons than astrocytes and ...OBJECTIVE Peroxisome proliferator activated receptor alpha(PPARα)is an important protective factor in neurovascular diseases such as ischemic stroke.Although PPARαexpression is higher in neurons than astrocytes and microglia,the pathophysiological functions of neuronal specific-PPARαin isch⁃emic stroke remains unknown.Here,we report that neuronal PPARαdeficiency is a key factor of neuronal injury.PPARαexpression markedly decreased in neurons after ischemic stroke.METHODS AND RESULTS Neuronal-specific PPARαknockout(NCKO)exacerbates neuronal damage and brain ischemic injury.PPARαdefi⁃ciency disrupts axonal microtubule organization and mitochondrial transport by decreasing the expression of dynein light chain Tctex-type 1(Dynlt1),which is implicated in cytoprotective role with damaged neurons.Furthermore,resto⁃ration of Dynlt1 expression in neurons of NCKO mice rescue mitochondrial transport disorder,cognitive deficits and brain ischemic injury asso⁃ciated with PPARαdeletion.CONCLUSION These results reveal a critical role for neuronal PPARαin ischemic brain injury by modulating axonal mitochondrial transportation.展开更多
文摘OBJECTIVE Peroxisome proliferator activated receptor alpha(PPARα)is an important protective factor in neurovascular diseases such as ischemic stroke.Although PPARαexpression is higher in neurons than astrocytes and microglia,the pathophysiological functions of neuronal specific-PPARαin isch⁃emic stroke remains unknown.Here,we report that neuronal PPARαdeficiency is a key factor of neuronal injury.PPARαexpression markedly decreased in neurons after ischemic stroke.METHODS AND RESULTS Neuronal-specific PPARαknockout(NCKO)exacerbates neuronal damage and brain ischemic injury.PPARαdefi⁃ciency disrupts axonal microtubule organization and mitochondrial transport by decreasing the expression of dynein light chain Tctex-type 1(Dynlt1),which is implicated in cytoprotective role with damaged neurons.Furthermore,resto⁃ration of Dynlt1 expression in neurons of NCKO mice rescue mitochondrial transport disorder,cognitive deficits and brain ischemic injury asso⁃ciated with PPARαdeletion.CONCLUSION These results reveal a critical role for neuronal PPARαin ischemic brain injury by modulating axonal mitochondrial transportation.
