Allogeneic grafts of fetal dopamine neurons: behavioral indices of immunological interactions.
Fetal central nervous system transplants to the adult brain have been utilized to understand brain connectivity and as replacement therapy in Parkinson's disease (PD). Here we use fetal brain allografting in the rat unilaterally depleted of dopamine, a unilateral model of PD, and apomorphine-induced rotations as an index of graft functional status while peripherally manipulating the host's alloimmune status. This system allows the investigator to examine, dynamically, host-allograft interactions in the brain under differing states of alloimmunoreactivity without the need to biopsy or sacrifice the animal. In addition to this novel application, we established that brain allografts are differentially susceptible to immunologic attack depending upon the graft's duration of residence in the host brain. Increasing residence time increases graft 'rejectability' to peripheral allosensitization. Passive immunization also sensitizes the host to subsequent graft rejection. Lastly, simple host alloimmunocompetence is necessary but not sufficient to cause fetal graft 'rejection', defined as a return of apomorphine-induced rotations.
Hudson
J L
JL
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262.
Hoffman
A
A
Strömberg
I
I
Hoffer
B J
BJ
Moorhead
J W
JW
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D016380:Brain Tissue Transplantation / Q000276:immunology* / Q000502:physiology; D004298:Dopamine / Q000502:physiology*; D016332:Fetal Tissue Transplantation / Q000276:immunology* / Q000502:physiology; D017072:Neostriatum / Q000502:physiology; D009474:Neurons / Q000276:immunology* / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011920:Rats, Inbred WF; D013239:Stereotyped Behavior / Q000187:drug effects
D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine