Investigating the potential effects of α-synuclein aggregation on susceptibility to chronic stress in a mouse Parkinson's disease model.
Chronic stress
Depression
Non-motor symptoms
Parkinson’s disease
Preformed fibrils
α-synuclein
Journal
Pharmacological reports : PR
ISSN: 2299-5684
Titre abrégé: Pharmacol Rep
Pays: Switzerland
ID NLM: 101234999
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
06
08
2023
accepted:
03
09
2023
revised:
30
08
2023
medline:
22
11
2023
pubmed:
19
9
2023
entrez:
19
9
2023
Statut:
ppublish
Résumé
Parkinson's disease (PD) is a motor disorder characterized by the degeneration of dopaminergic neurons, putatively due to the accumulation of α-synuclein (α-syn) in Lewy bodies (LBs) in Substantia Nigra. PD is also associated with the formation of LBs in brain areas responsible for emotional and cognitive regulation such as the amygdala and prefrontal cortex, and concurrent depression prevalence in PD patients. The exact link between dopaminergic cell loss, α-syn aggregation, depression, and stress, a major depression risk factor, is unclear. Therefore, we aimed to explore the interplay between sensitivity to chronic stress and α-syn aggregation. Bilateral injections of α-syn preformed fibrils (PFFs) into the striatum of C57Bl/6 J mice were used to induce α-syn aggregation. Three months after injections, animals were exposed to chronic social defeat stress. α-syn aggregation did not affect stress susceptibility but independently caused increased locomotor activity in the open field test, reduced anxiety in the light-dark box test, and increased active time in the tail suspension test. Ex vivo analysis revealed modest dopaminergic neuron loss in the substantia nigra and reduced dopaminergic innervation in the dorsal striatum in PFFs injected groups. α-Syn aggregates were prominent in the amygdala, prefrontal cortex, and substantia nigra, with minimal α-syn aggregation in the raphe nuclei and locus coeruleus. Progressive bilateral α-syn aggregation might lead to compensatory activity increase and alterations in emotionally regulated behavior, without affecting stress susceptibility. Understanding how α-syn aggregation and degeneration in specific brain structures contribute to depression and anxiety in PD patients requires further investigation.
Sections du résumé
BACKGROUND
BACKGROUND
Parkinson's disease (PD) is a motor disorder characterized by the degeneration of dopaminergic neurons, putatively due to the accumulation of α-synuclein (α-syn) in Lewy bodies (LBs) in Substantia Nigra. PD is also associated with the formation of LBs in brain areas responsible for emotional and cognitive regulation such as the amygdala and prefrontal cortex, and concurrent depression prevalence in PD patients. The exact link between dopaminergic cell loss, α-syn aggregation, depression, and stress, a major depression risk factor, is unclear. Therefore, we aimed to explore the interplay between sensitivity to chronic stress and α-syn aggregation.
METHODS
METHODS
Bilateral injections of α-syn preformed fibrils (PFFs) into the striatum of C57Bl/6 J mice were used to induce α-syn aggregation. Three months after injections, animals were exposed to chronic social defeat stress.
RESULTS
RESULTS
α-syn aggregation did not affect stress susceptibility but independently caused increased locomotor activity in the open field test, reduced anxiety in the light-dark box test, and increased active time in the tail suspension test. Ex vivo analysis revealed modest dopaminergic neuron loss in the substantia nigra and reduced dopaminergic innervation in the dorsal striatum in PFFs injected groups. α-Syn aggregates were prominent in the amygdala, prefrontal cortex, and substantia nigra, with minimal α-syn aggregation in the raphe nuclei and locus coeruleus.
CONCLUSIONS
CONCLUSIONS
Progressive bilateral α-syn aggregation might lead to compensatory activity increase and alterations in emotionally regulated behavior, without affecting stress susceptibility. Understanding how α-syn aggregation and degeneration in specific brain structures contribute to depression and anxiety in PD patients requires further investigation.
Identifiants
pubmed: 37725330
doi: 10.1007/s43440-023-00530-z
pii: 10.1007/s43440-023-00530-z
pmc: PMC10661792
doi:
Substances chimiques
alpha-Synuclein
0
Snca protein, mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1474-1487Subventions
Organisme : Narodowe Centrum Nauki
ID : 2018/02/X/NZ4/02712
Organisme : Academy of Finland
ID : #293392
Organisme : Academy of Finland
ID : #319195
Informations de copyright
© 2023. The Author(s).
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