It has been demonstrated in combined (raphé nuclei-hippocampus, cerebellum-hippocampus) organotypical cultures of the brain of newborn rats that, unlike cerebellar explants, the raphé nuclei grow in an oriented manner toward the hippocampus and exert a stimulating influence on its morphofunctional development; this is manifested: a) in an intense proliferation and migration of glial cells, which are accompanied by accelerated growth of neuronal processes and an increase in the dimensions of the initial piece; b) in the earlier formation of the background electrical activity of the neurons; c) in an increase in these cultures in the number of active cells; d) in a significant predominance of neurons with periodic (in the form of trains or groups) discharges. These data are in agreement with previously established effects of exogenous serotonin, and attest to an important role of the serotoninergic influences of the raphé nuclei in the morphofunctional development of the hippocampus.

A natural avermectin complex, aversectin C, was shown to be capable of exerting selective cytostatic and neurotoxic effects on mammalian cells. Specifically, it killed proliferating neuroblastoma B103 cells but was non-toxic for differentiated cells of this culture. The antiproliferation action of aversectin C was not inhibited by bicuculline or picrotoxin, antagonists of the GABAalpha receptors, and was partly due to the action of avermectin A1, a component of aversectin C. Aversectin C irreversibly suppressed activity of 60% neurons in medial septal slices of the rat brain. More than 55% of them were the GABAalpha- and B1-sensitive neurons whereas the rest, about 45% neurons, were the GABAalpha-insensitive and the neurotoxic effect of aversectin C was caused mainly by the B2 component.

SUMMARYTo determine whether primary fibroblasts producing latent transforming growth factor b 1 (TGF-b 1) are capable of down-regulating experimental autoimmune encephalomyelitis (EAE), a retroviral vector TGF-b 1-pBabe-neo ( -5 ¢ UTR) was used for efficient gene transfer into primary skin fibroblasts of DA rats. After heat activation, conditioned medium from the transduced fibroblasts was found to inhibit significantly in vitro proliferation of lymphocytes from lymph nodes of DA rats with EAE. Intraperitoneal administration of TGF-b 1 -transduced fibroblasts into DA rats during the priming phase of EAE resulted in a significant reduction in mortality and in the mean clinical and EAE scores versus the control immunized animals treated with non-transduced fibroblasts.

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