Embryonic striatal grafts restore neuronal activity of the globus pallidus in a rodent model of Huntington's disease
Section snippets
Experimental animals
Young adult male Sprague–Dawley rats (Charles River, Osaka), weighing 180–200 g at the start of the experiment, were used. They were maintained under a 12 h dark–light cycle with free access to food and water. All efforts were made to minimize animals suffering, to reduce the number of animals used, and to utilize alternatives to in vivo techniques, if available. All surgical procedures were performed under anesthesia with sodium pentobarbital (50 mg/kg, i.p.), except for electrophysiological
Apomorphine-induced rotational asymmetry
There was no significant difference in the rotational asymmetry between the groups before transplantation (P>0.05; Table 1). Six months after grafting, the animals with LGE grafts showed a significant reduction of the drug-induced turning compared to pregrafting scores (P<0.01; Table 1). No significant attenuation of the turning behavior was detected in the lesion control and MGE graft groups (P>0.05; Table 1). Indeed, one-way ANOVA with post hoc Scheffé's tests showed that at six months after
Cytochrome oxidase activity of the globus pallidus
There is a body of evidence to demonstrate that the activity of CO is regulated by changes in synaptic firing patterns or functional activity.[39]A large number of studies have employed CO histochemistry to detect the activity of CO.[39]The intensity of a visible reaction product in CO histochemistry is closely correlated with the biochemically detected activity of CO.8, 10, 30Previous studies investigating metabolic changes in several brain regions in animal with unilateral striatal lesions
Conclusions
The present study indicates the ability of the grafts to repair the functional aspect of the damaged striatopallidal pathway, which extends previous morphological data demonstrating neuronal connections between embryonic striatal grafts and the host GP,35, 36Since the striatal lesion-induced changes of the neuronal activity of striatofugal systems including the GP have been proposed to explain the mechanisms for movement disorders seen in Huntington's disease,6, 7, 25our results provide a
Acknowledgements
We are grateful to Drs P. Greegard and H. C. Hemmings Jr. for generous donation of the antibody against DARPP-32. This study was supported in part by a grant-in-aid for scientific research from the Ministry of Education, Japan.
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Cited by (38)
Mechanisms and use of neural transplants for brain repair
2017, Progress in Brain ResearchCitation Excerpt :The striatum has a central role in the selection and initiation of cortically derived plans for actions, and dysfunction following lesions, or in the human disease, is considered to be attributable to an essential disconnection of the corticostriatal (in particular frontostriatal) circuits that underpin goal-directed action (Rosvold, 1972). The observation that homotopic striatal grafts provide effective alleviation of motor, motor learning, and cognitive deficits in excitotoxic lesioned rats corroborates the hypothesis that homotopically placed striatal grafts can restore afferent and efferent circuitry in the adult nervous system (Fig. 1E), the substrates for which have been amply demonstrated at light microscopic (Wictorin, 1992), biochemical (Campbell et al., 1993; Sirinathsinghji et al., 1988, 1993), electrophysiological (Nakao et al., 1999; Rutherford et al., 1987; Xu et al., 1991), and ultrastructural (Clarke and Dunnett, 1993) levels of circuit analysis. Moreover, it is notable that striatal grafts placed into the globus pallidus (comparable to the ectopic placement of nigral grafts) is without functional efficacy (Isacson et al., 1986).
Clinical experience with stem cells and other cell therapies in neurological diseases
2013, Journal of the Neurological SciencesCitation Excerpt :Additional (and more convincing) proof came from animal studies. Over the past decade, clinching evidence has emerged regarding the capability of various stem cell populations to foster repair in animal models of neurological disorders such as PD, HD, MSA, ALS and AD, cerebral ischemia and multiple sclerosis [3–5,8,9,11–17,43–46]. NSC and MSC have shown an additional immunomodulatory effect, which may also contribute significantly to the clinical effects in inflammatory diseases such as MS [3,5,15,47].
Metabolic and electrophysiological changes in the basal ganglia of transgenic Huntington's disease rats
2012, Neurobiology of DiseaseSkilled motor control for the preclinical assessment of functional deficits and recovery following nigral and striatal cell transplantation
2012, Progress in Brain ResearchCitation Excerpt :Grafts release organotypic growth factors, restore the neurochemical, electrophysiological, and cellular composition in the striatum (Helm et al., 1990; Isacson et al., 1985, 1986; Mazzocchi-Jones et al., 2009; Sirinathsinghji et al., 1988), and reconnect appropriately afferent and efferent pathways including projections to the close target area, the globus pallidus (Clarke and Dunnett, 1993; Wictorin, 1992). More complex behaviors such as skilled hand use have been specifically investigated in rat and primate models before and after transplantation (Campbell et al., 1993; Döbrössy and Dunnett, 2006; Fricker et al., 1997; Fricker-Gates et al., 2004; Kendall et al., 1998; Mayer et al., 1992; Montoya et al., 1990; Nakao et al., 1996, 1999; Sirinathsinghji et al., 1988; Watts et al., 2000a). Most of the rat studies investigating the effects of transplantation have used the staircase test.
Technical factors that influence neural transplant safety in Huntington's disease
2011, Experimental NeurologyRotation, Drug-induced
2010, Encyclopedia of Movement Disorders, Three-Volume Set