title: Loss of dopaminergic neurons occurs in the ventral tegmental area and hypothalamus of rats following chronic stress: Possible pathogenetic loci for depression involved in Parkinson's disease.
abstract: Parkinson's disease (PD) is a neurodegenerative disease characterized by loss of dopaminergic (DA) neurons in the nigrostriatal and mesolimbic pathways including ventral tegmental area (VTA). Although several factors for the neuronal loss have been suggested, most of the PD cases are sporadic and idiopathic. In our previous study, we demonstrated the first evidence that solely chronic restraint stress (RS) induced the DA neuronal loss in the substantia nigra (SN). In this study, we further investigated whether chronic stress could affect other major DA systems, VTA and tuberoinfundibular system (TIDA), by using immunohistochemical and in situ hybridization techniques. The present study showed that, in the VTA, tyrosine hydroxylase (TH) immunoreactive neurons decreased by 9.8% at 2nd week, 19.2% at 4th week, 39.5% at 8th week, and 40.6% at 16th week during chronic RS as compared to control. Similarly, in the TIDA, the TH neurons decreased by 10.9% at 2nd week, 38.2% at 4th week, 56.3% at 8th week, and 57.1% at 16th week. The in situ hybridization results consistently demonstrated decreases in Th mRNA expressing cells in the VTA and TIDA in a comparable time dependent manner. Thus, exposure to chronic stress may simultaneously induce multiple neuronal loss of DA systems.
authors.affiliation: Department of Physiology, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8602, Japan. Electronic address: sugama@nms.ac.jp.
authors.forename: Shuei
authors.initials: S
authors.lastname: Sugama
authors.affiliation: Department of Physiology, Nippon Medical School, 1-1-5 Sendagi Bunkyo-ku, Tokyo 113-8602, Japan.
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Kakinuma
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood; D003863:Depression / Q000473:pathology*; D059290:Dopaminergic Neurons / Q000473:pathology*; D007031:Hypothalamus / Q000473:pathology*; D008297:Male; D017628:Microglia / Q000378:metabolism; D009410:Nerve Degeneration / Q000473:pathology; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000473:pathology* / Q000523:psychology; D017208:Rats, Wistar; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000473:pathology*; D013997:Time Factors; D017557:Ventral Tegmental Area / Q000473:pathology*
chemical_list: D003345:Corticosterone
keywords: Arcuate nucleus; Dopamine; Hypothalamus; Immunohistochemistry; Parkinson's disease; Stress; Tyrosine hydroxylase; Ventral tegmental area