Microglia senescence occurs in both substantia nigra and ventral tegmental area.
Parkinson's disease
aging-dependent neurodegeneration
dopamine neurons
microglia complexity
stereological analyses
tyrosine hydroxylase; microglia senescence
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
13
12
2019
revised:
19
03
2020
accepted:
24
03
2020
pubmed:
11
4
2020
medline:
1
12
2021
entrez:
11
4
2020
Statut:
ppublish
Résumé
During aging humans lose midbrain dopamine neurons, but not all dopamine regions exhibit vulnerability to neurodegeneration. Microglia maintain tissue homeostasis and neuronal support, but microglia become senescent and likely lose some of their functional abilities. Since aging is the greatest risk factor for Parkinson's disease, we hypothesized that aging-related changes in microglia and neurons occur in the vulnerable substantia nigra pars compacta (SNc) but not the ventral tegmental area (VTA). We conducted stereological analyses to enumerate microglia and dopaminergic neurons in the SNc and VTA of 1-, 6-, 9-, 18-, and 24-month-old C57BL/J6 mice using sections double-stained with tyrosine hydroxylase (TH) and Iba1. Both brain regions show an increase in microglia with aging, whereas numbers of TH+ cells show no significant change after 9 months of age in SNc and 6 months in VTA. Morphometric analyses reveal reduced microglial complexity and projection area while cell body size increases with aging. Contact sites between microglia and dopaminergic neurons in both regions increase with aging, suggesting increased microglial support/surveillance of dopamine neurons. To assess neurotrophin expression in dopaminergic neurons, BDNF and TH mRNA were quantified. Results show that the ratio of BDNF to TH decreases in the SNc, but not the VTA. Gait analysis indicates subtle, aging-dependent changes in gait indices. In conclusion, increases in microglial cell number, ratio of microglia to dopamine neurons, and contact sites suggest that innate biological mechanisms compensate for the aging-dependent decline in microglia morphological complexity (senescence) to ensure continued neuronal support in the SNc and VTA.
Identifiants
pubmed: 32275335
doi: 10.1002/glia.23834
pmc: PMC8356201
mid: NIHMS1709141
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
Tyrosine 3-Monooxygenase
EC 1.14.16.2
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2228-2245Subventions
Organisme : NINDS NIH HHS
ID : R01 NS071122
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG052258
Pays : United States
Organisme : NIA NIH HHS
ID : R37 AG036800
Pays : United States
Organisme : NINDS NIH HHS
ID : F32 NS010310
Pays : United States
Organisme : NINDS NIH HHS
ID : R21 NS103108
Pays : United States
Organisme : NIH HHS
ID : S10 OD020026
Pays : United States
Organisme : NIDA NIH HHS
ID : R21 DA043895
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA026947
Pays : United States
Informations de copyright
© 2020 Wiley Periodicals, Inc.
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