ASTROCYTES AND EXTRACELLULAR-MATRIX FOLLOWING INTRACEREBRAL TRANSPLANTATION OF EMBRYONIC VENTRAL MESENCEPHALON OR LATERAL GANGLIONIC EMINENCE

Transplantation of embryonic neurons to the adult mammalian central ne rvous system (CNS) offers the possibility of re-establishing neural fu nctions lost after traumatic injuries or neurodegenerative disease. In the adult CNS, however, transplanted neurons and their growing neurit es can become confined to the graft region, and there may also be a re lative paucity of afferents innervating grafted neurons. Because glia may influence the development and regeneration of CNS neurons, the pre sent study has characterized the distribution of astrocytes and develo pmentally regulated glycoconjugates (chondroitin-6-sulfate proteoglyca n and tenascin) within regions of the embryonic mouse CNS used as dono r tissues, and in and around these grafts to the adult striatum and su bstantia nigra. Both chondroitin-6-sulfate proteoglycan and tenascin a re present in the embryonic ventral mesencephalon (in association with radial glia and their endfeet, and glial boundaries that cordon off t he ventral mesencephalon dopamine neuron migratory zone) and lateral g anglionic eminence before transplantation, and they are conserved with in grafts of these tissues to the adult mouse. Neostriatal grafts exhi bit a heterogeneous pattern of astrocyte and extracellular matrix mole cule distribution, unlike ventral mesencephalon grafts, which are rath er homogeneous. There is evidence to suggest that, in addition to vari ation in astroglial/extracellular matrix immunostaining within differe nt compartments in striatal grafts to either adult striatum or substan tia nigra, there are also boundaries between these compartments that a re rich in glial fibrillary acidic protein/extracellular matrix compon ents. Substantia nigra grafts, with cells immunoreactive for tyrosine hydroxylase, are also rich in immature astroglia (RC-2-immunopositive) , and as the astroglia mature (to glial fibrillary acidic protein-posi tive) over time the expression of chondroitin-6-sulfate proteoglycan a nd tenascin is also reduced. These same extracellular matrix constitue nts, however, are only slightly up-regulated in an area of the adult h ost which surrounds the grafted tissue. Glial scar components exhibit no obvious differences between grafts from different sources to homoto pic (e.g., striatum to striatum) or heterotopic (e.g., substantia nigr a to striatum) sites, and likewise grafts of non-synaptically associat ed structures (e.g., cerebellum to striatum), needle lesions or vehicl e injections all yield astroglial/extracellular matrix scars in the ho st that are indistinguishable. Studies utilizing the ROSA-26 transgeni c (beta-galactosidase-positive) mouse as a host for -chloro-3-indolyl- beta-d-galactopyranoside-labeled grafts indicate that the early astrog lial/extracellular matrix response to the graft is derived from the su rrounding host structures. Furthermore, biochemical analysis of one of the ''boundary molecules'', tenascin, from the developing ventral mes encephalon versus adult striatal lesions, suggests that different form s of the molecule predominate in the embryonic versus lesioned adult b rain. Such differences in the nature and distribution of astroglia and developmentally regulated extracellular matrix molecules between dono r and host regions may affect the growth and differentiation of transp lanted neurons. The present study suggests that transplanted neurons a nd their processes may flourish within graft versus host regions, in p art due to a confining glial scar, but also because the extracellular milieu within the graft site remains more representative of the develo pmental environment from which the donor neurons were obtained [Gates M. A., et at. (1994) Sec. Neurosci Abstr. 20, 471]. Copyright (C) 1996 IBRO. Published by Elsevier Science Ltd.