[Abstract Title]. - Society for Neuroscience

Title: Enzymatic digestion of chondroitin sulphate proteoglycans and transplantation of ES cellderived
dopamine neurons in the substantia nigra of hemi-parkinsonian rats
Authors: *N. DIAZ, F. DIAZ, I. VELASCO;
Univ. Natl. Autonoma Mexico, Inst. Fisiol Ceular, Mexico City, Mexico
Abstract: Cell therapy in animal models of Parkinson‟s disease has been successful when
dopaminergic cells are grafted in the striatal area. Intranigral transplantation of these cells has
only been effective when combined with intrastriatal grafting, and the therapeutic benefit has
been associated with striatal dopamine release. One of the major difficulties for nigral grafting
and its association with behavioral recovery is that the adult brain is a restrictive environment for
axonal growth due to expression of components of the extracellular matrix especially chondroitin
sulphate proteoglycans (CSPG). In this work, we evaluated if intranigral transplantation of
dopamine neurons differentiated from embryonic stem (ES) cells, combined with enzymatic
digestion of CSPG with chondroitinase ABC (ChABC) might contribute to anatomical and
functional regeneration of the nigro-striatal pathway in a rat model of the Parkinson‟s disease.
We differentiated ES cells to dopamine neurons in vitro and grafted them in 3 experimental
groups: 1) striatum; 2) angle injection to reach the substantia nigra; 3) intranigral transplantation
together with ChABC injection in the striatal direction. In all animals, we performed behavioral
tests to establish functional recovery of the experimental procedures. We found that intrastriatal
transplantation caused recovery in pharmacological and non-pharmacological behavioral test.
Intranigral transplantation without ChABC did not cause behavioral recovery. We observed an
increase in the reactivity of CSPG and glial fibrillary acidic protein along the injection in the
groups transplanted in the substantia nigra. Addition of ChABC showed partial degradation of
proteoglycans as evidenced by the use of 2B6 antibody, which recognizes a partially degraded
form of CSPG. The group with transplant in the substantia nigra and enzymatic degradation
presented significant improvement in the stepping test, in contrast with the group transplanted in
the substantia nigra without ChABC. However, the rotational test did not show recovery in the
nigral graft plus ChABC. These results indicate that the addition of ChABC might be used to
promote partial functional recovery in the diseased adult brain.
Disclosures: N. Diaz , None; F. Diaz, None; I. Velasco, None.
Poster
247. Parkinson's Disease Interventions: Animal and Clinical Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 247.21/T4
Topic: C.02.d. Therapies