Behavioral defects associated with amygdala and cortical dysfunction in mice with seeded α-synuclein inclusions
| Autor: | Ashwin Narayanan, David G. Standaert, Aseel Dib, Laura A. Volpicelli-Daley, Drake R. Thrasher, Jennifer Freire, Drèson L. Russell, Lindsay E. Stoyka, Andrew E. Arrant, Casey L. Mahoney |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine Conditioning Classical Parkinson’s disease dementia Fear conditioning Substantia nigra Lewy neurites Biology Parkinson's disease dementia Amygdala Article lcsh:RC321-571 Alpha-synuclein 03 medical and health sciences 0302 clinical medicine Dopamine Cortex (anatomy) medicine Animals Dementia with Lewy Bodies Prefrontal cortex lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Cerebral Cortex Inclusion Bodies Neurons Social dominance Behavior Animal Dementia with Lewy bodies Pars compacta Dopaminergic Parkinson Disease medicine.disease Corpus Striatum nervous system diseases Excitatory neurons Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure nervous system Neurology Rotarod Performance Test Cortex Fibrils Female Lewy bodies Neuroscience 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neurobiology of disease Neurobiology of Disease, Vol 134, Iss, Pp-(2020) |
| ISSN: | 0969-9961 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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