Role of Minocycline in the Inhibition of Microglial Activation and Protection of Dopaminergic Neurons in 6-OHDA Induced Parkinsonian Animal Model

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Yi He, M.D. Ph.D.
Baylor College of Medicine, Texas

Abstract

Microglia are neural cells thought to be involved in neuronal degeneration in the PD brain, as well as in animal models of parkinsonism bought about by the neurotoxin, MPTP. Apoptosis is a type of cell death seen in PD brains that may be caused by toxic products made by activated microglia. Dr. Yi He of Baylor College of Medicine (Houston) will use another mouse model (6-OHDA lesioned) in an attempt to slow cell degradation and apoptosis with an anti-inflammatory drug, minocycline, a son of tetracycline. Inhibiting microglial activation, he thinks, can protect dopaminergic cells against programmed cell death.

Progress Report (as of 3/2003)

Gliosis means an increase in the number of glial (support) cells present. Seen prominently in pathologic studies, it was thought to have a housekeeping role, i.e., removing dead cells. Of late, many scientists believe gliosis can also add to neurodegeneration. One type of glial cell, microglia, are thought to play a role in the degeneration of the substantia nigra pars compacta (SNpc), the brain area most affected in PD patients. Dr. Yi He and his Baylor University group (Houston) have used their funds to show that the anti-inflammatory drug minocycline (in dosages they’ve found appropriate) can short-circuit the activation of microglial cells and thereby protect SNpc dopaminergic cells in parkinsonian mice. Appropriate funding credit has been included in resulting publications. It is known that lipopolysaccharides (LPS) activate microglial cells; if minocycline can protect against this cell toxicity in animals, a clinical trial in human patients is likely to be the next step. Their final report concludes that they are preparing an NIH proposal based on data showing restoration of glial cell function.

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