Mice lacking the peroxisome proliferator-activated receptor alpha gene present reduced number of dopamine neurons in the substantia nigra without altering motor behavior or dopamine neuron decline over life

R. Gonzalez-Aparicio, J. A. Flores, Inmaculada Tasset, I. Tunez, E. Fernandez-Espejo

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)161-169
Number of pages9
JournalNeuroscience
Volume186
DOIs
StatePublished - Jul 14 2011
Externally publishedYes

Fingerprint

PPAR alpha
Dopaminergic Neurons
Motor Neurons
Peroxisome Proliferator-Activated Receptors
Substantia Nigra
Genes
Antioxidants
Oxidative Stress
Neurons
Interleukin-3
Locomotion
Dopamine
Cell Death
Down-Regulation
Enzyme-Linked Immunosorbent Assay
Cytokines

Keywords

  • Aging
  • Dopamine
  • Oxidation
  • PPAR-α
  • Substantia nigra

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Mice lacking the peroxisome proliferator-activated receptor alpha gene present reduced number of dopamine neurons in the substantia nigra without altering motor behavior or dopamine neuron decline over life. / Gonzalez-Aparicio, R.; Flores, J. A.; Tasset, Inmaculada; Tunez, I.; Fernandez-Espejo, E.

In: Neuroscience, Vol. 186, 14.07.2011, p. 161-169.

Research output: Contribution to journalArticle

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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.",
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