Intraocular and intracranial transplantation of neural tissue : Studies on hypothalamic and hippocampal neuros

Abstract: Previous studies has demonstrated the possibility to transplant monoaminergic neurons intracranially and to the anterior chamber of the eye, where these neurons continue to develop into functional, transmitter expressing cells. In the present study, investigations were undertaken to examine the development of transplanted hypothalamic and hippocampal neurons in the rat. The intention was to examine synaptic maturation in the isolated brain tissue and the possibility of histaminergic neurons to survive transplantation intraocularly and intracranially into the denervated hippocampus. Properties such as fiber ingrowth into eo-transplanted tissue, electrophysiological activity and histaminergic H3-receptor response, and influence of hypothalamic tissue on eo-transplanted tissues were evaluated. Synaptic maturation was studied using an immunoblot assay of the synapsin I and II proteins and synapsin immunohistochemistry. The hypothalamic grafts were examined with immunohistochemistry and histamine assay of the levels of histamine in the transplants. Electrophysiological recordings of single cell activity was used to study the effect of H3-receptor agonist and antagonist. The isolated intra ocular transplants of hippocampal tissue developed significant amounts of synapsin proteins with an overall distribution pattern as in the hippocampus in situ. Histaminergic neurons in the hypothalamic transplants survived transplantation both intraocularly and intracranially. The neurons were found to send neurites into the host iris and into eo-grafted CNS tissue. The hypothalamic transplants were also found to have a stimulatory effect on the growth of eo-grafted hippocampal tissue and on pyramidal cell differentiation. Neurons within the hypothalamic transplants exhibited spontaneous activity that was suppressed upon agonist stimulation of H3-receptors. These findings demonstrate that histaminergic neurons grow and develop in transplanted hypothalamic tissue and that neurons in these transplants expressed histamine and functional H3-receptors.