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Behavioral defects associated with amygdala and cortical dysfunction in mice with seeded α-synuclein inclusions.
- Source :
-
Neurobiology of disease [Neurobiol Dis] 2020 Feb; Vol. 134, pp. 104708. Date of Electronic Publication: 2019 Dec 16. - Publication Year :
- 2020
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Abstract
- Parkinson's disease (PD) is defined by motor symptoms such as tremor at rest, bradykinesia, postural instability, and stiffness. In addition to the classical motor defects that define PD, up to 80% of patients experience cognitive changes and psychiatric disturbances, referred to as PD dementia (PDD). Pathologically, PD is characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and intracellular inclusions, called Lewy bodies and Lewy neurites, composed mostly of α-synuclein. Much of PD research has focused on the role of α-synuclein aggregates in degeneration of SNpc dopamine neurons because of the impact of loss of striatal dopamine on the classical motor phenotypes. However, abundant Lewy pathology is also found in other brain regions including the cortex and limbic brain regions such as the amygdala, which may contribute to non-motor phenotypes. Little is known about the consequences of α-synuclein inclusions in these brain regions, or in neuronal subtypes other than dopamine neurons. This project expands knowledge on how α-synuclein inclusions disrupt behavior, specifically non-motor symptoms of synucleinopathies. We show that bilateral injections of fibrils into the striatum results in robust bilateral α-synuclein inclusion formation in the cortex and amygdala. Inclusions in the amygdala and prefrontal cortex primarily localize to excitatory neurons, but unbiased stereology shows no significant loss of neurons in the amygdala or cortex. Fibril injected mice show defects in a social dominance behavioral task and fear conditioning, tasks that are associated with prefrontal cortex and amygdala function. Together, these observations suggest that seeded α-synuclein inclusion formation impairs behaviors associated with cortical and amygdala function, without causing cell loss, in brain areas that may play important roles in the complex cognitive features of PDD.<br /> (Copyright © 2019. Published by Elsevier Inc.)
- Subjects :
- Amygdala metabolism
Animals
Behavior, Animal drug effects
Cerebral Cortex metabolism
Conditioning, Classical
Corpus Striatum drug effects
Female
Inclusion Bodies metabolism
Male
Mice, Inbred C57BL
Neurons metabolism
Neurons pathology
Parkinson Disease metabolism
Parkinson Disease pathology
Parkinson Disease psychology
Rotarod Performance Test
alpha-Synuclein administration & dosage
Amygdala pathology
Behavior, Animal physiology
Cerebral Cortex pathology
Inclusion Bodies pathology
alpha-Synuclein metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1095-953X
- Volume :
- 134
- Database :
- MEDLINE
- Journal :
- Neurobiology of disease
- Publication Type :
- Academic Journal
- Accession number :
- 31837424
- Full Text :
- https://doi.org/10.1016/j.nbd.2019.104708