Cholinergic Plasticity and the Meaning of Death

  • Michael McKinney
  • Karen Baskerville
  • David Personett
  • Katrina Williams
  • John Gonzales


The selective degeneration of basal forebrain cholinergic neurons in several major human brain diseases has been known now for several decades, but why these cells die is still a puzzle. Our research addressing mechanisms of selective cholinergic vulnerability is structured by a hypothesis of multiple insults, one of which is oxidative stress. In our rodent model of aging, we have obtained convincing evidence that brain oxidative stress is associated with cognitive decline. The age-related oxidative stress may be global in nature, and probably includes effects on cholinergic neurons. This chapter first describes the anatomy and physiology of several major central cholinergic populations. We then summarize how we are using multiple models and experimental approaches to address how these populations might differ with respect to their vulnerability to oxidative stress, in particular nitrosative stress. The discussion is placed within the context of recent technological developments in brain research involving microarray screening of gene expression. Several examples are given to show how these technologies can be applied to discovery of neuronal signaling pathways likely to be important in human disease conditions. Finally, we outline some of the ways we are employing these methods in studies of the vasculature of the brain to address issues in stroke biology.


Nitric Oxide Nitric Oxide Cholinergic Neuron Basal Forebrain Cholinergic System 
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© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Michael McKinney
    • 1
  • Karen Baskerville
    • 1
  • David Personett
    • 1
  • Katrina Williams
    • 1
  • John Gonzales
    • 1
  1. 1.Department of PharmacologyMayo ClinicJacksonvilleUSA

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