Dissociation between dopaminergic response and motor behavior following intrastriatal, but not intravenous, transplant of bone marrow mononuclear stem cells in a mouse model of Parkinson’s disease

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Abstract

Parkinson’s disease is characterized by the progressive loss of dopaminergic neurons from the substantia nigra, a process that leads to a dopamine deficiency in the striatum. This deficiency is responsible for the development of motor symptoms, including resting tremor, bradykinesia, rigidity and postural instability. Based on the observation of substantial neuronal death, alternatives to Parkinson’s disease treatment have been studied, including cell-based therapies. The present study aimed to assess the therapeutic potential of intravenous and intrastriatal transplant of bone marrow mononuclear cells in a mouse model of Parkinson’s disease. Animals underwent stereotaxic surgery and received an injection of 6-hydroxydopamine into their medial forebrain bundle. Three weeks later, mice were injected with bone marrow mononuclear cells or saline through the caudal vein or directly into their right striatum. Motor function was assessed using the rotarod and apomorphine-induced rotation tests. Our results showed that intrastriatal bone marrow mononuclear cells, but not intravenous, have a short-term therapeutic effect on dopaminergic response in this mice model of parkinsonism assessed by the apomorphine-induced rotation test. This phenomenon was not identified on the rotarod test, showing dissociation between dopaminergic response and motor behavior. Further experiments are needed to elucidate the precise mechanisms involved in these effects.

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