Native expression of voltage-gated potassium channels in the mouse striatum and their plasticity in models of Parkinson’s and Alzheimer’s diseases

  • Babajide Adegbuyi Otuyemi

Student thesis: Doctoral Thesis

Abstract

Disruption of the normal patterns of expression, localisation and function of potassium channels in brain neurons has emerged as a likely pathophysiological basis for stress-induced mental illnesses, Parkinson’s and Alzheimer’s disease, with the striatum as a particular brain region of interest. Among the major classes of potassium channels, voltage-gated potassium channels are known to play a major role in regulating neuronal excitability. However, expression of voltage-gated potassium channel subtypes in the striatum have not been well established. In this research, a mouse model of early life stress was used for chronic stress while SNCH-OVX and APPPSEN1 transgenic mouse models were used to model Parkinson’s and Alzheimer’s disease respectively and compared to their wild type littermates as controls to investigate how the native expression patterns of different voltage-gated potassium channel sub-families within the mouse striatum changes in response to stress and pathology associated with Parkinson’s and Alzheimer’s disease. This led to the characterisation of the expression patterns of different voltage-gated potassium channel subtypes and the neurochemical inputs they integrate in the striatum. Furthermore, the data indicated voltage-gated potassium channels to be highly plastic in response to life experience, provided insights into the earliest functional changes in Parkinson’s disease, and showed the resilience of striatal neurochemicals to Alzheimer’s disease pathology. Therefore, psychosocial stress and neurodegenerative disease pathology alters the expression of specific voltage-gated potassium 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.
Date of AwardApr 2020
Original languageEnglish
Awarding Institution
  • University of Portsmouth
SupervisorMarisa Van Der Merwe (Supervisor) & Jerome Swinny (Supervisor)

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