Frontiers Journal of Neurology & Neuroscience

Changes In Native Expression Of Voltage Gated Potassium Channels In The Mouse Striatum In Parkinson’s And Alzheimer’s Diseases

Abstract

Introduction: Disruption of the normal patterns of expression, localization, and function of potassium channels in brain neurons has emerged as a likely pathophysiological basis for Parkinson’s and Alzheimer’s disease. Among the major classes of potassium channels, voltage- gated potassium channels (Kv) are known to play a major role in regulating neuronal excitability. However, expression of Kv subtypes in the striatum have not been well established.

Objectives: The primary objective of this study was to determine the native expression patterns of different Kv sub-families within the mouse striatum and how this changes in animals models of Parkinson’s and Alzheimer’s disease (AD; PD).

Methods: The SNCH-OVX and APP-PSEN1 transgenic mouse models were used to model PD and AD respectively, and compared to their wild type (WT) littermates as controls. Immunohistochemistry and confocal microscopy was used to assess the effect of AD and PD pathology on the location of Kv protein within different types of neurons of the striatum. Quantitative reverse transcription polymerase chain reaction (qPCR) was used to assess Kv changes at the mRNA level.

Results: Immunohistochemistry revealed the localisation of Kv2.1 on the somata of medium spiny neurons, Kv4.2 on dendrites and Kv4.3 on GABAergic interneurons. qPCR revealed specific change in the expression of Kv4.3 and tyrosine hydroxylase at the mRNA level. Further immunohistochemistry studies revealed specific change in the expression of Kv4.3 and dopamine receptors at the protein level.

Conclusion: Neurodegenerative disease pathology alters the expression of specific Kv channels, in distinct cell types of the striatum. The expected changes in neuronal excitability arising from such changes could contribute to pathology of such conditions.

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