Open AccessDelayed transplantation of precursor cell‐derived astrocytes provides multiple benefits in a rat model of P arkinsons
Author(s) -
Proschel Christoph,
Stripay Jennifer L,
Shih ChungHsuan,
Munger Joshua C,
Noble Mark D
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.1002/emmm.201302878
Subject(s) - transplantation , glial cell line derived neurotrophic factor , tyrosine hydroxylase , parvalbumin , dopaminergic , biology , neurotrophic factors , neuroscience , microbiology and biotechnology , dopamine , medicine , biochemistry , receptor
In addition to dopaminergic neuron loss, it is clear that Parkinson disease includes other pathological changes, including loss of additional neuronal populations. As a means of addressing multiple pathological changes with a single therapeutically‐relevant approach, we employed delayed transplantation of a unique class of astrocytes, GDA s BMP , that are generated in vitro by directed differentiation of glial precursors. GDA s BMP produce multiple agents of interest as treatments for PD and other neurodegenerative disorders, including BDNF , GDNF , neurturin and IGF 1. GDA s BMP also exhibit increased levels of antioxidant pathway components, including levels of NADPH and glutathione. Delayed GDA BMP transplantation into the 6‐hydroxydopamine lesioned rat striatum restored tyrosine hydroxylase expression and promoted behavioral recovery. GDA BMP transplantation also rescued pathological changes not prevented in other studies, such as the rescue of parvalbumin + GABA ergic interneurons. Consistent with expression of the synaptic modulatory proteins thrombospondin‐1 and 2 by GDA s BMP , increased expression of the synaptic protein synaptophysin was also observed. Thus, GDA s BMP offer a multimodal support cell therapy that provides multiple benefits without requiring prior genetic manipulation.