Long-term TGFbeta2 protein expression in heterotopic cortical grafts located in the rat striatum

Purpose: Transforming growth factor beta 2 (TGFbeta2) is a multifunctional cytokine thought to play a crucial role in neuronal growth, differ-entiation and survival. In the cortex of adult rats, TGFbeta2 is constitutively expressed in a subset of neurons and astrocytes. In the present study we analyzed whether TGFbeta2 is also present in intrastriatal transplants of cortical anlage. In addition we investigated the temporo-spatial expression pattern of TGFbeta2 in the surrounding host striatum. Methods: Cortical primordia of rat fetuses (E14) were stereotactically grafted into the rostral striatum of adult recipient rats. Grafts were allowed to differentiate for 1, 2, 3, 4, 8 weeks or one year, respectively, followed by morphological and immunohistochemical analysis. Results: From week 2 on, TGFbeta2-immunoreactivity (IR) was detectable in transplanted neurons. Within the graft, GFAP-IR was already present one week after transplantation, whereas TGFbeta2-immunostained astrocytes were first seen after 2 weeks. One year after transplanta-tion, TGFbeta2 positive neurons and astrocytes were still present. In the host striatum and at the graft-host interface an increase of TGFbeta2-immu-noreactive astrocytes first occured after one week both in grafted animals and in sham-operated (lesioning without grafting) rats. Conclusions: Our data suggest that at least a subpopulation of transplanted neurons develops a phenotype as cortical neurons in situ with respect to TGFbeta2 expression. Upregulation of astrocytic TGFbeta2 expression within the graft, however, is due to the trauma imposed by the transplantation procedure rather than an intrinsic differentiation program of co-grafted astrocytes.