Dataset Information

Exercise Promotes Neurite Extensions from Grafted Dopaminergic Neurons in the Direction of the Dorsolateral Striatum in Parkinson's Disease Model Rats.

ABSTRACT: BACKGROUND:Cell transplantation is expected to be a promising treatment for Parkinson's disease (PD), in which re-innervation of the host striatum by grafted dopamine (DA) neurons is essential. In particular, the dorsolateral part of the striatum is important because it is the target of midbrain A9 DA neurons, which are degenerated in PD pathology. The effect of exercise on the survival and maturation of grafted neurons has been reported in several neurological disease models, but never in PD models. OBJECTIVE:We investigated how exercise influences cell transplantation for PD, especially from the viewpoint of cell survival and neurite extensions. METHODS:Ventral mesencephalic neurons from embryonic (E12.5) rats were transplanted into the striatum of adult 6-OHDA-lesioned rats. The host rats then underwent treadmill training as exercise after the transplantation. Six weeks after the transplantation, they were sacrificed, and the grafts in the striatum were analyzed. RESULTS:The addition of exercise post-transplantation significantly increased the number of surviving DA neurons. Moreover, it promoted neurite extensions from the graft toward the dorsolateral part of the striatum. CONCLUSIONS:This study indicates a beneficial effect of exercise after cell transplantation in PD.

SUBMITTER: Torikoshi S

PROVIDER: S-EPMC7242856 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Exercise Promotes Neurite Extensions from Grafted Dopaminergic Neurons in the Direction of the Dorsolateral Striatum in Parkinson's Disease Model Rats.

Torikoshi Sadaharu S Morizane Asuka A Shimogawa Takafumi T Samata Bumpei B Miyamoto Susumu S Takahashi Jun J

Journal of Parkinson's disease 20200101 2

<h4>Background</h4>Cell transplantation is expected to be a promising treatment for Parkinson's disease (PD), in which re-innervation of the host striatum by grafted dopamine (DA) neurons is essential. In particular, the dorsolateral part of the striatum is important because it is the target of midbrain A9 DA neurons, which are degenerated in PD pathology. The effect of exercise on the survival and maturation of grafted neurons has been reported in several neurological disease models, but never ...[more]

PMID: 31929121

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Project description:The pathological hallmark of Parkinson's disease is the degeneration of dopaminergic nigrostriatal neurons, leading to depletion of striatal dopamine. Recent neuroanatomical work has identified pathways for communication across striatal subdivisions, suggesting that the striatum provides a platform for integration of information across parallel corticostriatal circuits. The aim of this study was to investigate whether dopaminergic dysfunction in Parkinson's disease was associated with impairments in functional connectivity across striatal subdivisions, which could potentially reflect reduced integration across corticostriatal circuits. Utilizing resting-state functional magnetic resonance imaging (fMRI), we analyzed functional connectivity in 39 patients with Parkinson's disease, both "on" and "off" their regular dopaminergic medications, along with 40 age-matched healthy controls. Our results demonstrate widespread impairments in connectivity across subdivisions of the striatum in patients with Parkinson's disease in the "off" state. The administration of dopaminergic medication significantly improved connectivity across striatal subdivisions in Parkinson's disease, implicating dopaminergic deficits in the pathogenesis of impaired striatal interconnectivity. In addition, impaired striatal interconnectivity in the Parkinson's disease "off" state was associated with pathological decoupling of the striatum from the thalamic and sensorimotor (SM) networks. Specifically, we found that although the strength of striatal interconnectivity was positively correlated with both (i) the strength of internal thalamic connectivity, and (ii) the strength of internal SM connectivity, in both healthy controls and the Parkinson's disease "on" state, these relationships were absent in Parkinson's disease when in the "off" state. Taken together our findings emphasize the central role of dopamine in integrated striatal function and the pathological consequences of striatal dopamine denervation in Parkinson's disease.

Dataset Information

Exercise Promotes Neurite Extensions from Grafted Dopaminergic Neurons in the Direction of the Dorsolateral Striatum in Parkinson's Disease Model Rats.

Publications

Exercise Promotes Neurite Extensions from Grafted Dopaminergic Neurons in the Direction of the Dorsolateral Striatum in Parkinson's Disease Model Rats.

Similar Datasets

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