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Distribution and neuroprotective role of Latent Transforming growth factor binding proteins in the central nervous system of Rodent and human


Transforming Growth Factor betas (TGFßs) regulate the formation and degradation of the extracellular matrix and the growth and differentiation of various cell types in different organs. Latent Transforming Growth Factor Binding Proteins (LTBPs) are needed for secretion, correct folding and matrix deposition of TGFßs.

In the brain, TGFß1 is inducible by ischemia, while ß2 and ß3 are present constitutively in several regions. Strong evidence indicates that TGFß1 has neuroprotective functions. The exact role and the topographical distribution of LTBPs in the brain are unknown.

We assume that the four known members of LTBPs also play a role in the processing of TGFßs in the nervous system. My preliminary in situ hybridization histochemical studies clearly show t hat LTBPs are present in the adult rat brain. High LTBP1 expression levels are seen in the medial preoptic area, the anteromedial thalamus and some cerebral cortical regions, low expression levels in the septum, hippocampus and hypothalamic nuclei.

LTBP2, an exceptional member of the LTBP protein family (no binding to TGFßs) is expressed only in cortical areas, hippocampus, and the perifornical/dorsolateral hypothalamus. LTBP3 exhibits a wider expression profile with the strongest expression in the ventral pallidum, anterodorsal and reticular thalamic nuclei, hippocampus, cortex, red nucleus and the periaqueductal gray.

The objective of the application is to initiate a research project on the distribution and function of LTBPs in the brain based on these new preliminary data, my background in neurochemistry and molecular biology and the exceptional technical repertoir provided by the host laboratory including experimental modeling of brain ischemia, a variety of advanced immuno-histochemical techniques and processing of samples in one of the largest human brain tissue banks.

Altogether, these opportunities can provide a foundation for a long-term investigation of TGFßs in rodent and human nervous systems.


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