title: Comparison of the structure, function and autophagic maintenance of mitochondria in nigrostriatal and tuberoinfundibular dopamine neurons.
abstract: A pathological hallmark of Parkinson׳s disease (PD) is progressive degeneration of nigrostriatal dopamine (NSDA) neurons, which underlies the motor symptoms of PD. While there is severe loss of midbrain NSDA neurons, tuberoinfundibular (TI) DA neurons in the mediobasal hypothalamus (MBH) remain intact. In the present study, confocal microscopic analysis revealed that mitochondrial content and numbers of mitophagosomes were lower in NSDA neuronal cell bodies in the substantia nigra pars compacta (SNpc) compared to TIDA neuronal cell bodies in the arcuate nucleus (ARC) of C57BL/6J male mice. Mitochondrial respiration, mass, membrane potential and morphology were determined using bioenergetic, flow cytometric and transmission electron microscopic analyses of synaptosomes isolated from discrete brain regions containing axon terminals of NSDA and TIDA neurons. Maximum and spare respiratory capacities, and mitochondrial mass were lower in synaptosomal mitochondria derived from the striatum (ST) as compared with the MBH, which correlated with lower numbers of mitochondria per synaptosome in these brain regions. In contrast, there was no regional difference in mitochondrial basal, maximum or spare respirations following inhibition of Complex I activity with rotenone. These results reveal that higher numbers of viable mitochondria are correlated with more extensive autophagic mitochondrial quality maintenance in TIDA neurons as compared with NSDA neurons.
authors.affiliation: Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, MI, USA; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
authors.forename: Hae-Young
authors.initials: HY
authors.lastname: Hawong
authors.affiliation: Genetics Program, Michigan State University, East Lansing, MI, USA.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Patterson
authors.affiliation: Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA.
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Winner
authors.affiliation: Department of Neurology and Ophthalmology, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA; Neuroscience Program, Michigan State University, East Lansing, MI, USA; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA.
authors.forename: John L
authors.initials: JL
authors.lastname: Goudreau
authors.affiliation: Genetics Program, Michigan State University, East Lansing, MI, USA; Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, USA; Neuroscience Program, Michigan State University, East Lansing, MI, USA; College of Osteopathic Medicine, Michigan State University, East Lansing, MI, USA. Electronic address: lookingl@msu.edu.
authors.forename: Keith J
authors.initials: KJ
authors.lastname: Lookingland
mesh_terms: D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000378:metabolism*; D001343:Autophagy / Q000502:physiology*; D019069:Cell Respiration / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000166:cytology / Q000378:metabolism*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D065842:Pars Compacta / Q000166:cytology / Q000378:metabolism*; D012402:Rotenone / Q000494:pharmacology; D013574:Synaptosomes / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D014475:Uncoupling Agents; D012402:Rotenone; D014446:Tyrosine 3-Monooxygenase; D042967:Electron Transport Complex I
keywords: Autophagy; Confocal microscopy; Flow cytometry; Mediobasal hypothalamus; Mitochondria; Neurodegeneration; Nigrostriatal DA neurons; Parkinson disease; Respiration; Striatum; Substantia nigra; Transmission electron microscopy; Tuberoinfundibular DA neurons