Transplantation of retinoic acid treated murine embryonic stem cells & behavioural deficit in Parkinsonian rats.

Background & objectives: Stem cell therapy has been considered as an ideal option for the treatment of Parkinson’s disease. Murine embryonic stem cells (mESCs)-derived dopaminergic (DA) neurons may substitute the degenerated neurons in the brain. In this study we generated highly enriched cultures of neural progenitors from mESCs and grafted them into the striatum of Parkinsonian rats to evaluate their ability to improve impaired function. Methods: An animal model was developed for Parkinson’s disease in rats, using 6- hydroxy dopamine. The animals were divided into two groups: (i) the control group treated with culture medium only, and (ii) the experimental group, which was treated with a murine ESC cell-line (CCE). Transplanted cells were labelled with bromodeoxyuridine (BrdU), exposed to retinoic acid and then engrafted within the striatum of the rat model. Results: Treated ES cells by retinoic acid were found to relieve apomorphine-induced asymmetric motor behaviour. Immunohistochemistry results revealed tyrosine hydroxlase immunoreactivity in engrafted cells 15 days after transplantation. Further, the ultrastructural examination along with cresyl violet staining confirmed that the cells gained neuronal and glial appearance. Interpretation & conclusions: Our data demonstrate that retinoic acid treatment and transplanting ESC cells to the lessioned brain can lead to the generation of putative dopaminergic neurons and functional recovery in parkinsonian rat model with.

Increased Burst Firing in Substantia Nigra Pars Reticulata Neurons and Enhanced Response to Selective D2 Agonist in Hemiparkinsonian Rats After Repeated Administration of Apomorphine

Intermittent administrations of dopaminergic agents in hemiparkinsonian rat enhances the behavioral response to subsequent administration of the drugs. This phenomenon is known as "priming" and thought as comparable to drug-induced dyskinesia in patients with Parkinson's disease. We investigated the behavioral and electrophysiological changes in 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats after repeated administrations of apomorphine. Administration of apomorphine (0.32 mg/kg, intraperitoneal, i.p.) twice daily for 6 days enhanced the rotation induced by apomorphine from 341 turns/hour at the beginning to 755 turns/hr at the end. At the same time, the response to selective D2 agonist quinpirole (0.26 mg/kg, i.p.) was also enhanced from 203 to 555 turns/hr. Extracellular single unit recording revealed no significant difference in the basal firing rates of substantia nigra pars reticulata (SNr) neurons between the ipsilateral and contralateral side of the 6-OHDA lesion regardless of the repeated administrations of apomorphine. In SNr of the lesion side, the units with burst firing pattern were found more frequently after repeated administrations of apomorphine and the suppressive effect of quinpirole on the firing rate was enhanced. These findings suggest that the increased percentage of the burst units is the important electrophysiological change in the development of enhanced response to selective D2 agonist.