Striatal, ventral mesencephalic and cortical transplants into the intact rat striatum: a neuroanatomical study.
Intrastriatal transplantation of fetal striatal (STR), cortical (CTX), or ventral mesencephalic (VM) tissue into the normal striatum has been shown to produce behavioral deficits (38). Here, we have examined the cellular elements of the transplants and their connectivity with the host using histochemistry for cytochrome oxidase (CO) and acetylcholinesterase (AChE), immunocytochemistry for glial fibrillary acidic protein (GFAP), OX42, tyrosine hydroxylase (TH), dopamine beta-hydroxylase (DBH), serotonin (5-HT), and cholecystokinin (CCK). Autoradiography for dopamine D1 and D2, muscarinic cholinergic, and serotonin 5-HT1 and 5-HT2 receptors at 5-15 months after transplantation was also investigated. CO staining showed that all transplants were metabolically active. The STR and VM transplants contained AChE-positive neurons and fibers. The CTX transplants exhibited AChE terminals with an appearance similar to that of the host cortex. AChE staining within the STR transplants was patchy. 5-HT-, TH-, and DBH-immunoreactive (IR) fibers were found in the STR and CTX transplants. In two of six CTX transplants, many TH-IR neurons were present. The VM transplants contained many TH-IR, 5-HT-IR, and DBH-IR cell bodies and fibers. CCK-IR stain was found in the VM transplant and was coextensive with regions containing TH-IR cell bodies. Fibers stained by all markers crossed the transplant and host border. Receptor autoradiography revealed that muscarinic cholinergic and 5-HT2 receptors were present in the STR, CTX, and VM transplants. In addition, dopamine D1 and D2 receptors were present in the STR transplants. Intermittent heavy staining for GFAP and OX42 were observed along the border of most transplants and the hosts. It was noted that high densities and hypertrophy of GFAP- or OX42-stained astrocytes or microglia, respectively, were present in the transplants and adjacent host. OX42-stained macrophages were found in many transplants. The present results indicate that intrastriatal transplants into the intact normal brain express numerous histochemical, immunocytochemical, and receptor features characteristic of the appropriate adult tissues. The afferents from the host extend into the STR and CTX transplants, and neural fibers from the VM transplants grew into surrounding host tissue, suggesting possible anatomical connection. Ultrastructural evidence is needed to determine if these fibers form synaptic connections. The results from GFAP and OX42 immunocytochemical staining support the possibility suggested by behavioral studies that damage to the host brain is induced by neural transplantation.
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Department of Psychiatry, University of Cincinnati College of Medicine, Ohio 45267-0559.
Shipley
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Norman
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Sanberg
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D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001679:Biogenic Amines / Q000378:metabolism; D016380:Brain Tissue Transplantation; D002540:Cerebral Cortex / Q000166:cytology*; D003342:Corpus Striatum / Q000166:cytology* / Q000378:metabolism / Q000502:physiology*; D016332:Fetal Tissue Transplantation; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006085:Graft Survival; D006651:Histocytochemistry; D007150:Immunohistochemistry; D008297:Male; D008636:Mesencephalon / Q000166:cytology*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000378:metabolism
D001679:Biogenic Amines; D005904:Glial Fibrillary Acidic Protein; D017981:Receptors, Neurotransmitter; D000110:Acetylcholinesterase