Investigating the potential effects of α-synuclein aggregation on susceptibility to chronic stress in a mouse Parkinson's disease model.

Autor: Alwani A; Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland., Maziarz K; Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland., Burda G; Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland., Jankowska-Kiełtyka M; Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland., Roman A; Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland., Łyszczarz G; Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland., Er S; Faculty of Pharmacy, Drug Research Program, University of Helsinki, Helsinki, Finland.; Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland., Barut J; Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland., Barczyk-Woźnicka O; Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387, Kraków, Poland., Pyza E; Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Gronostajowa 9, 30-387, Kraków, Poland., Kreiner G; Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland., Nalepa I; Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland., Chmielarz P; Department of Brain Biochemistry, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343, Kraków, Poland. chmiel@if-pan.krakow.pl.
Jazyk: angličtina
Zdroj: Pharmacological reports : PR [Pharmacol Rep] 2023 Dec; Vol. 75 (6), pp. 1474-1487. Date of Electronic Publication: 2023 Sep 19.
DOI: 10.1007/s43440-023-00530-z
Abstrakt: 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: 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: 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: 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
Externí odkaz: