Parkinson’s Disease

Cross section of the brain illustrating how TGFα acts to
repair damage in the brains of animal models with Parkinson’s disease (PD)

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Right side: Key brain structures involved, including the striatum, the pallidum, the thalamus, and the midbrain dopamine neurons of the substantia nigra-ventral tegmental area.

Left side: the cortical-striatal pallidal-nigral-thalamic-cortical “loop." In PD, the dopamine neurons degenerate and their connection to the striatal neurons is lost. TGFα infused into the striatum, or delivered intranasally, induces the adult stem cells lining the ependymal and subventricular zone adjacent to the striatum to divide (proliferate) in great numbers.

Parkinson's disease sagittal (side) view after TGFα is either infused into the striatum or delivered intranasally

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Hundreds of thousands to millions of new progenitors then migrate to the regions of the striatum where they differentiate into neurons that have dopamine markers.

Parkinson's disease detail

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Parkinson's disease exploded view

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The presence of these new dopaminergic neurons is associated with dramatic improvement in sensorimotor and motor behavior.

Further characterization of the TGFα-induced striatal ridge cells in animal model (slides)

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Rats receiving an infusion of TGFα after brain injury to the striatum (cartooned in purple) demonstrate massive proliferation of stem cells in the subventricular zone (SVZ), which migrate in a ridge toward the site of the injury. New cells express markers of differentiating glial cells and neurons.

Adapted from Fallon et al., 2000, 2006 View full article

Further characterization of migratory ridge cells by using fluorescence immunohistochemistry for neuronal markers

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There is dense positive staining for BrdUrd (a), ß-tubulin (b and c), and doublecortin (d and e). Labeling of the same section for DAT (f), and BrdUrd (g) reveals that some neurons are double-labeled for both markers (h). White arrows on f-h point to double-labeled neurons, lateral ventricle.