Long-term survival of grafted cells, dopamine synthesis/release, synaptic connections, and functional recovery after transplantation of fetal nigral cells in rats with unilateral 6-OHDA lesions in the nigrostriatal dopamine pathway
| Autor: | Miharu Kanai, Hitoo Nishino, Fujiya Furuyama, Takeshi Hashitani, Sadao Shiosaka, Michiko Kumazaki, Haruhiko Sato, Yoshiaki Isobe, Nakazo Watari |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
medicine.medical_specialty
Tyrosine 3-Monooxygenase Cell Survival Dopamine Neurotoxins Caudate nucleus Nigrostriatal pathway Substantia nigra Motor Activity Biology Methamphetamine Hydroxydopamines chemistry.chemical_compound Catecholamines Fetal Tissue Transplantation Internal medicine medicine Animals Brain Tissue Transplantation Oxidopamine Molecular Biology Tyrosine hydroxylase General Neuroscience Homovanillic acid Brain Rats Inbred Strains Dendrites Corpus Striatum Rats Substantia Nigra Transplantation Microscopy Electron Endocrinology medicine.anatomical_structure chemistry Synapses Female Neurology (clinical) Caudate Nucleus Neuroscience Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 534:83-93 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/0006-8993(90)90115-r |
| Popis: | In animal models of hemi-Parkinson's disease, survival of grafted nigral cells, their synaptic connections, dopamine (DA) synthesis/release, and recovery from motor disturbances were investigated, and these were compared among 3 groups of animals raised for 3 months, 1 year and 2 years after the transplantation. Fetal nigral DAergic cell suspensions were transplanted in the ipsilateral caudate nucleus of rats with unilateral 6-OHDA lesions in the nigrostriatal DA pathway. Motor disturbances, assessed by methamphetamine-induced rotation, recovered partly in the 2nd week, significantly in the 4th week after the grafting, and remained stable thereafter. Many tyrosine hydroxylase (TH)-positive cells were detected along the grafting tracks. The number of TH-positive cells was similar in the 3 groups of animals. These TH-positive cells made synaptic connections in the host caudate. By in vivo microdialysis measurement, extracellular DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) around the grafted sites recovered to 30–100% of those of controls. No significant differences were observed in the concentration of DA, DOPAC and HVA among 3 groups of animals. They also responded to methamphetamine loading though the magnitudes were smaller. Using a TH cDNA probe, TH-positive cells were found to express TH mRNA in in situ hybridization-autoradiographic analysis. Data indicate that grafted fetal DAergic cells survive, synthesize and release. DA, make synaptic connections in the host brain and ameliorate motor disturbances for over 2 years. There were no differences in these parameters among the 3 groups of animals, and no untoward side effects were observed event at 2 years after the grafting. Thus it was confirmed that the grafting of neuronal cells into the brain is a promising approach to restore disturbed function. |
| Databáze: | OpenAIRE |
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