Partial microglial depletion is associated with impaired hippocampal synaptic and cognitive function in young and aged rats.
aging
cognition
hippocampus
microglial depletion
microglial repopulation
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
revised:
25
01
2021
received:
22
10
2020
accepted:
26
01
2021
pubmed:
16
2
2021
medline:
10
2
2022
entrez:
15
2
2021
Statut:
ppublish
Résumé
The role of microglia in mediating age-related changes in cognition and hippocampal synaptic function was examined by microglial depletion and replenishment using PLX3397. We observed age-related differences in microglial number and morphology, as well as increased Iba-1 expression, indicating microglial activation. PLX3397 treatment decreased microglial number, with aged rats exhibiting the lowest density. Young rats exhibited increased expression of pro-inflammatory cytokines during depletion and repopulation and maintenance of Iba-1 levels despite reduced microglial number. For aged rats, several cytokines increased with depletion and recovered during repopulation; however, aged rats did not fully recover microglial cell number or Iba-1 expression during repopulation, with a recovery comparable to young control levels rather than aged controls. Hippocampal CA3-CA1 synaptic transmission was impaired with age, and microglial depletion was associated with decreased total synaptic transmission in young and aged rats. A robust decline in N-methyl-d-aspartate-receptor-mediated synaptic transmission arose in young depleted rats specifically. Microglial replenishment normalized depletion-induced synaptic function to control levels; however, recovery of aged animals did not mirror young. Microglial depletion was associated with decreased context-object discrimination memory in both age groups, which recovered with microglial repopulation. Aged rats displayed impaired contextual and cued fear memory, and microglial replenishment did not recover their memory to the level of young. The current study indicates that cognitive function and synaptic transmission benefit from the support of aged microglia and are hindered by removal of these cells. Replenishment of microglia in aging did not ameliorate age-related cognitive impairments or senescent synaptic function.
Identifiants
pubmed: 33586813
doi: 10.1002/glia.23975
pmc: PMC8278544
mid: NIHMS1709147
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1494-1514Subventions
Organisme : NIA NIH HHS
ID : R01 AG052258
Pays : United States
Organisme : NIA NIH HHS
ID : R56 AG037984
Pays : United States
Organisme : NIA NIH HHS
ID : P30 AG028740
Pays : United States
Organisme : NIA NIH HHS
ID : R21 AG068205
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG037984
Pays : United States
Informations de copyright
© 2021 Wiley Periodicals LLC.
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