title: Differences in Number of Midbrain Dopamine Neurons Associated with Summer and Winter Photoperiods in Humans.
abstract: Recent evidence indicates the number of dopaminergic neurons in the adult rodent hypothalamus and midbrain is regulated by environmental cues, including photoperiod, and that this occurs via up- or down-regulation of expression of genes and proteins that are important for dopamine (DA) synthesis in extant neurons ('DA neurotransmitter switching'). If the same occurs in humans, it may have implications for neurological symptoms associated with DA imbalances. Here we tested whether there are differences in the number of tyrosine hydroxylase (TH, the rate-limiting enzyme in DA synthesis) and DA transporter (DAT) immunoreactive neurons in the midbrain of people who died in summer (long-day photoperiod, n = 5) versus winter (short-day photoperiod, n = 5). TH and DAT immunoreactivity in neurons and their processes was qualitatively higher in summer compared with winter. The density of TH immunopositive (TH+) neurons was significantly (~6-fold) higher whereas the density of TH immunonegative (TH-) neurons was significantly (~2.5-fold) lower in summer compared with winter. The density of total neurons (TH+ and TH- combined) was not different. The density of DAT+ neurons was ~2-fold higher whereas the density of DAT- neurons was ~2-fold lower in summer compared with winter, although these differences were not statistically significant. In contrast, midbrain nuclear volume, the density of supposed glia (small TH- cells), and the amount of TUNEL staining were the same in summer compared with winter. This study provides the first evidence of an association between environmental stimuli (photoperiod) and the number of midbrain DA neurons in humans, and suggests DA neurotransmitter switching underlies this association.
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Tim D
authors.initials: TD
authors.lastname: Aumann
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Mai
authors.initials: M
authors.lastname: Raabus
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Doris
authors.initials: D
authors.lastname: Tomas
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Agustinus
authors.initials: A
authors.lastname: Prijanto
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Leonid
authors.initials: L
authors.lastname: Churilov
authors.affiliation: Neurobiology Section, Division of Biological Sciences and Center for Neural Circuits and Behavior, University of California San Diego, La Jolla, California, 92093-0357, United States of America.|Kavli Institute for Brain and Mind, University of California San Diego, La Jolla, California, 92093-0357, United States of America.
authors.forename: Nicholas C
authors.initials: NC
authors.lastname: Spitzer
authors.affiliation: Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Malcolm K
authors.initials: MK
authors.lastname: Horne
mesh_terms: D000328:Adult; D000368:Aged; D002452:Cell Count; D004298:Dopamine / Q000032:analysis / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000166:cytology* / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008636:Mesencephalon / Q000166:cytology* / Q000378:metabolism; D008875:Middle Aged; D009457:Neuroglia / Q000166:cytology / Q000378:metabolism; D017440:Photoperiod; D012621:Seasons; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism
chemical_list: D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine