Mast cells in the brain: Development and function

Mast cells originate in the bone marrow and migrate to tissues where they differentiate. Their vasoactive functions are well known in the periphery but not in the CNS. In ring doves, large numbers of mast cells suddenly appear in the medial habenula of adult subjects after a brief period of courtship. The current thesis aims to study mast cell differentiation and function in the CNS using this animal model.;Experiment 1 demonstrates for the first time in situ differentiation of mast cells in the neuropil of the CNS. Mast cells in the medial habenula of 1 month old birds are immature with low-sulfated glycosaminoglycans. Many of them can be identified under electron microscope but are not detectable by mast cell markers. In the medial habenula of 6 month old birds, mast cells obtain highly-sulfated glycosaminoglycans. The gradual increase in the number of detectable mast cells during development is attributable to their infiltration and differentiation.;Experiment 2 suggests that an intrinsic factor(s) produced by the medial habenula is responsible for mast cell infiltration and survival. In both intraventricular and intraocular transplantation, grafts from habenula of day 14-15 embryos have mast cells while control grafts from optic tectum do not. However, habenula grafts do not support full maturation of mast cells. In addition, host endocrine state does not regulate mast cell number in habenula grafts. In host but not grafted medial habenula, significantly fewer mast cells were found in castrated birds than in peripubertal intact birds.;Experiment 3 provides evidence that degranulation of brain mast cells locally alters the blood-brain barrier. After degranulation of mast cells by the secretogogue compound 48/80, and after quantitative examination of the dye in the medial habenula and control areas, the fluorescent tracer Evans blue is found in the medial habenula, but it is excluded from this nucleus in control birds. These studies indicate bi-directional interactions between mast cells and the CNS.