Embryonic MGE Precursor Cells Grafted into Adult Rat Striatum Integrate and Ameliorate Motor Symptoms in 6-OHDA-Lesioned Rats

Abstract

SUMMARY We investigated a strategy to ameliorate the motor symptoms of rats that received 6-hydroxydopamine (6-OHDA) lesions, a rodent model of Parkinson’s disease, through transplantation of embryonic medial ganglionic eminence (MGE) cells into the striatum. During brain development, embryonic MGE cells migrate into the striatum and neocortex where they mature into GABAergic interneurons and play a key role in establishing the balance between excitation and inhibition. Unlike most other embryonic neurons, MGE cells retain the capacity for migration and integration when transplanted into the postnatal and adult brain. We performed MGE cell transplantation into the basal ganglia of control and 6-OHDA-lesioned rats. Transplanted MGE cells survived, differentiated into GABA+ neurons, integrated into host circuitry, and modifed motor behavior in both lesioned and control rats. Our data suggest that MGE cell transplantation into the striatum is a promising approach to investigate the potential benefits of remodeling basal ganglia circuitry in neurodegenerative diseases.

GABAergic Precursor Transplantation into the Prefrontal Cortex Prevents Phencyclidine-Induced Cognitive Deficits

“…Tra, Training; Ret, retention; CTX, cortex; n.s., not significant. transplanted cells to survive and/or differentiate into certain interneuron subtypes according to the cortical areas into which they had been transplanted, the transplanted MGE cells were highly motile, dispersed widely, and intermingled with the endogenous neurons in both neonatal and adult brain (Wichterle et al, 1999;Alvarez-Dolado et al, 2006;Martínez-Cerdeño et al, 2010;Southwell et al, 2010;present study). We hypothesize that the cortical neuronal network is largely permissive for functional integration of transplanted MGE cells, and that the basal excitation/inhibition ratio in the PFC can be readjusted to prevent behavioral abnormalities in the host.…”

“…MGE cell transplantation increases GABA-mediated inhibition on host projection neurons and modulates host neuronal circuitry and its activity (Alvarez-Dolado et al, 2006;Baraban et al, 2009;Southwell et al, 2010;Zipancic et al, 2010). Their transplantation reduces seizures (Baraban et al, 2009;Zipancic et al, 2010), ameliorates motor deficits (Martínez-Cerdeño et al, 2010) and induces cortical plasticity (Southwell et al, 2010).…”

Activin induces cortical interneuron identity and differentiation in embryonic stem cell-derived telencephalic neural precursors

“…their regulation of cortical activity [10][11][12][13] . They are also involved in a number of neuropsychiatric illnesses, including epilepsy, autism and schizophrenia 11,47 .…”

“…Special attention has been paid to cortical interneurons owing to their remarkable migratory capacity in postnatal cortex, their stereotypic differentiation after transplantation and their regulation of cortical activity [10][11][12][13] . The serum-free monolayer differentiation protocol allows to obtain in a reproducible manner relatively pure populations of telencephalic neural progenitor cells that respond to Shh signalling in the same way as occurs during normal development 14,15 .…”

Neuroprotective effect of Portulaca oleracea extracts against 6-hydroxydopamine-induced lesion of dopaminergic neurons

“…One of the underling mechanisms of cell death is oxidative stress, which has gained special attention because of its association with the reported H 2 O 2 and free radical formation, decreased superoxide dismutase (SOD) activity, increased monoaminoxidase (MAO) activity and mitochondrial complex toxicity (Martínez-Cerdeño et al 2010, Decressac et al 2012.…”