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.
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.
Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil; Laboratory of Neurosciences and Cellular Signaling, Institute of Biomedical Research and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil.
Caroline
C
Calice da Silva
Laboratory of Neurosciences and Cellular Signaling, Institute of Biomedical Research and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil.
Bárbara Nunes
BN
Azevedo
Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil; Laboratory of Molecular and Cellular Biology, Institute of Biomedical Research, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil.
Denise Cantarelli
DC
Machado
Department of Biochemistry, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, 90035-003, Brazil.
Eduardo R
ER
Zimmer
Department of Biochemistry, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, RS, 90035-003, Brazil.
Leo Anderson Meira
LAM
Martins
Postgraduate Program in Medicine and Health Sciences, Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil; Laboratory of Neurosciences and Cellular Signaling, Institute of Biomedical Research and Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, 90619-900, Brazil. Electronic address: jcc@pucrs.br.
Jaderson Costa
JC
da Costa
D061605:Administration, Intravenous; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage; D003342:Corpus Striatum / Q000601:surgery*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000008:administration & dosage; D059290:Dopaminergic Neurons / Q000187:drug effects* / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009043:Motor Activity; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000503:physiopathology / Q000517:prevention & control*; D045442:Rotarod Performance Test; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology
D018491:Dopamine Agonists; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D016627:Oxidopamine; D001058:Apomorphine
Intrastriatal; Intravenous; Motor behavior; Mouse; Parkinson’s disease; Stem cell