Analysis of primary visual cortex in dementia with lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations

Khundakar, Ahmad A; Hanson, Peter S; Erskine, Daniel; Lax, Nichola Z; Roscamp, Joseph; Karyka, Evangelia; Tsefou, Eliona; Singh, Preeti; Cockell, Simon J; Gribben, Andrew; Ramsay, Lynne; Blain, Peter G; Mosimann, Urs Peter; Lett, Deborah J; Elstner, Matthias; Turnbull, Douglass M; Xiang, Charles C; Brownstein, Michael J; O'Brien, John T; Taylor, John-Paul; ... (2016). Analysis of primary visual cortex in dementia with lewy bodies indicates GABAergic involvement associated with recurrent complex visual hallucinations. Acta neuropathologica communications, 4(1), p. 66. BioMed Central 10.1186/s40478-016-0334-3

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Dementia with Lewy bodies (DLB) patients frequently experience well formed recurrent complex visual hallucinations (RCVH). This is associated with reduced blood flow or hypometabolism on imaging of the primary visual cortex. To understand these associations in DLB we used pathological and biochemical analysis of the primary visual cortex to identify changes that could underpin RCVH. Alpha-synuclein or neurofibrillary tangle pathology in primary visual cortex was essentially absent. Neurone density or volume within the primary visual cortex in DLB was also unchanged using unbiased stereology. Microarray analysis, however, demonstrated changes in neuropeptide gene expression and other markers, indicating altered GABAergic neuronal function. Calcium binding protein and GAD65/67 immunohistochemistry showed preserved interneurone populations indicating possible interneurone dysfunction. This was demonstrated by loss of post synaptic GABA receptor markers including gephyrin, GABARAP, and Kif5A, indicating reduced GABAergic synaptic activity. Glutamatergic neuronal signalling was also altered with vesicular glutamate transporter protein and PSD-95 expression being reduced. Changes to the primary visual cortex in DLB indicate that reduced GABAergic transmission may contribute to RCVH in DLB and treatment using targeted GABAergic modulation or similar approaches using glutamatergic modification may be beneficial.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > University Psychiatric Services > University Hospital of Geriatric Psychiatry and Psychotherapy
10 Strategic Research Centers > ARTORG Center for Biomedical Engineering Research > ARTORG Center - Gerontechnology and Rehabilitation

UniBE Contributor:

Mosimann, Urs Peter

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2051-5960

Publisher:

BioMed Central

Language:

English

Submitter:

Vanessa Vallejo

Date Deposited:

16 Mar 2017 13:48

Last Modified:

17 Mar 2017 10:53

Publisher DOI:

10.1186/s40478-016-0334-3

PubMed ID:

27357212

Uncontrolled Keywords:

Alzheimer’s disease; Dementia with Lewy bodies; Hallucinations; Primary visual cortex; α-synuclein

BORIS DOI:

10.7892/boris.94151

URI:

https://boris.unibe.ch/id/eprint/94151

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