Michael A. Collins, PhD
Department of Microbiology and Immunology
1962 University of Vermont
1968 Purdue University
Mediators/mechanisms of neurodegeneration and neuroprotection
Research in the Collins' laboratory, done in collaboration with Dr. E.J. Neafsey, neuroanatomy professor, focuses on brain neurodegeneration and/or neuroprotection mechanisms during (a) alcohol intake and (b) parkinsonism. (a) Daily "binge" exposure to high alcohol levels causes cortical and hippocampal degeneration in vivo (adult rats) and in organotypic rat brain slices in long-term culture. The binge alcohol-induced neurodamage appears to involve brain hydration rather than synaptic excitotoxicity, since diuretic agents that prevent brain edema are neuroprotective whereas antagonists to glutamate receptors, calcium channels, and nitric oxide are not. Initial findings indicate that alcohol bingeing promotes a glial-dependent, neuroinflammatory-like process involving TNF alpha, arachidonic acid, and oxidative stress. In contrast, pre-conditioning brain cultures with moderate (non-toxic) levels of alcohol inhibits several potent neurotoxins such as HIV-1 proteins gp120, Tat or gp41, or Alzheimer's disease protein, beta-amyloid.
This novel alcohol pre-conditioning neuroprotection may result in part from suppression of glial mechanisms initiated by these neurotoxins, as well as from elevations in neuroprotective heat shock proteins. (b) Since Parkinson's disease has an environmental component, we have studied with rodents and brain cultures whether relatively common heterocyclics found in foods and smoke (beta-carbolines, e.g. norharman) are pro-neurotoxins that may act like MPTP which is a synthetic N-methylated pyridine used to cause parkinsonism in animal models. We and others have shown that brain enzymes can N-methylate carbolines, that the N-methylated products are neurotoxic in vivo and in vitro in rats, and that methylated carbolines appear elevated along with N-methylase activity in parkinsonian brain.