title: Mice lacking the peroxisome proliferator-activated receptor α gene present reduced number of dopamine neurons in the substantia nigra without altering motor behavior or dopamine neuron decline over life.
abstract: Peroxisome proliferator-activated receptor alpha (PPAR-α), which is expressed by neurons of the nigrostriatal circuit, plays a prominent role in oxidative stress and neuroinflammation. The objectives were: (i) to discern if levels of antioxidant molecules and pro-inflammatory cytokines, along with PPAR-γ expression are modified in the nigrostriatal region of null PPAR-α mice, (ii) to discern whether dopaminergic neuronal features of the substantia nigra pars compacta (SNpc) and dorsal striatum are affected in null mice, and (iii) to establish if aging-induced decline of nigral neurons is different in null PPAR-α mice relative to wild-type littermates. A substantial decrease in antioxidant molecules was found in SNpc of null mice, by using ELISA. The pro-inflammatory factors TNF-α and IL-3 were found to be reduced in the substantia nigra, suggesting dual and opposite effects of PPAR-α deficiency on oxidative and pro-inflammatory molecules. Immunohistological and stereological studies revealed that young null mice present a smaller SNpc (-19.8%; TH downregulation was discarded). Normal locomotion in an open-field was not affected in null mice. Dopamine cell death could be caused by reduced protection against oxidative stress. Old null mice showed a percentage reduction of nigral dopamine neurons similar to that of young null animals, with a rate of decline over life of around 44%, the same value than that of wild-type littermates. These findings suggest that nuclear PPAR-α is necessary for the normal development of the substantia nigra along with normal levels of antioxidant molecules. Lack of PPAR-α does not modify the normal motor behavior of mice or decline of nigral dopamine neurons throughout life.
authors.affiliation: Departamento de Fisiologia Medica y Biofisica, Universidad de Sevilla, Av. Sánchez Pizjuán 4, 41009 Sevilla, Spain.
authors.forename: R
authors.initials: R
authors.lastname: Gonzalez-Aparicio
authors.forename: J A
authors.initials: JA
authors.lastname: Flores
authors.forename: I
authors.initials: I
authors.lastname: Tasset
authors.forename: I
authors.initials: I
authors.lastname: Tunez
authors.forename: E
authors.initials: E
authors.lastname: Fernandez-Espejo
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology*; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D013378:Substantia Nigra / Q000473:pathology* / Q000502:physiology
chemical_list: D000975:Antioxidants; D047493:PPAR alpha; D004298:Dopamine