http://tinyurl.com/87byybj

University of Kentucky UKnowledge
Theses and Dissertations-Anatomy and Neurobiology
2011
Anatomy and Neurobiology
NIGROSTRIATAL DOPAMINE-NEURON FUNCTION FROM NEUROTROPHIC-LIKE PEPTIDE TREATMENT AND NEUROTROPHIC FACTOR DEPLETION

Overall, this body of work examines novel synthetic peptides with potential to enhance DA-neuron function and expands upon the current understanding of GDNF’s role in the nigrostriatal pathway.

(incredibly dense material, though introductory info useful for anatomy and physiology of nigrostriatal pathway)

Madelyn, thanks for posting this. I took the time to plow through most of the thesis and found it extremely pertinent.

This work expands on previous studies demonstrating that small peptide fragments of GDNF which are naturally derived from the protein have neurotrophic properties similar to GDNF itself. Like GDNF, their effects are focused on the dopamine neurons lost in PD.

One significance of this is that these peptides, being small molecules, are much more likely to be able to cross the blood brain barrier, possibly having been administered through the nose.

Another feature of this work is the use of a unique mouse model of PD in which one of the two normal alleles of the GDNF gene is "knocked out". The result is that the nigrostriatal neurons of these mice are slowly lost, resulting in decreased movement. These mice are also much more sensitive than normal mice to toxins like MPTP.

Robert

Thank you Robert. I had not read past the introductory information, but was impressed with its detail. madelyn