Schwann-like macroglia in adult rat brain.

Olfactory ensheathing cells (OECs) share properties with astrocytes and Schwann cells. This study was designed to test the hypothesis that glia with properties similar to those exhibited by OECs might be present in brain areas other than the olfactory bulb. We found tanycytes and pituicytes to express a distinctive set of immunological markers in common with OECs and nonmyelinating Schwann cells, namely low-affinity neurotrophin receptor (p75NTR), O4 antigen, estrogen receptor-alpha type, and insulin-like growth factor 1 (IGF-1). The two glial types could be cultured from adult hypothalamus and neurohypophysis, respectively, using the methods developed for olfactory OECs. Both glial types displayed morphologies reminiscent of Schwann cells, in primary culture. Schwann-like central glia presented a preferred growth substrate for dorsal root ganglion neurites and, when making intimate contacts with them, manifested a myelinating phenotype. These combined properties define a type of CNS macroglia that would not fit within conventional central glia types.

Differential effects of glycosaminoglycans on neurite outgrowth from hippocampal and thalamic neurones.

Chondroitin sulphate proteoglycans are expressed in a temporally restricted pattern from embryonic day 17 to postnatal day 0 in both the thalamus and the cortical subplate, to which thalamic neurones transiently project. To study whether chondroitin sulphate proteoglycans could be specifically involved in the modulation of thalamic axon outgrowth, we compared neurite outgrowth from cultured rat embryonic hippocampal and thalamic neurones, in the presence of chondroitin sulphate type C (isolated from shark cartilage) and chondroitin sulphate type B (dermatan sulphate; isolated from bovine mucosa). When added to the culture medium, both types of glycosaminoglycan lowered the adhesion to laminin and polylysine of both hippocampal and thalamic neurones. However, only chondroitin sulphate specifically modified the pattern of thalamic but not hippocampal neurone outgrowth, promoting axon growth. The morphological changes induced by chondroitin sulphate were concentration dependent and correlated with the selective binding of chondroitin sulphate to the neuronal plasma membrane and its subsequent internalisation. Chondroitin sulphate loosely bound to the surface of hippocampal neurones, but was not internalised. These results indicate that proteoglycans, and in particular the glycosaminoglycan component of these molecules, can differentially modulate neurite outgrowth, depending on their biochemical composition and on the type of neurones they bind to; this would be a possible mechanism of controlling axon guidance in vivo.

Induction of a neurite-promoting factor in rat brain following injury or deafferentation.

Ablation of the entorhinal/occipital cortex in young adult rats caused a several-fold increase in the neurite-promoting activity in extracts of the tissue surrounding the wound and in areas that had been deafferented by the lesion. The time course of induction closely paralleled reactive axon sprouting in the deafferented hippocampus, with maximal levels of neurite-promoting activity reached between 9 and 15 days post-lesion. Aged animals, in which reactive sprouting is deficient, showed no increase in activity by 12 days after deafferentation of the hippocampus. The neurite-promoting activity of brain extracts was non-diffusible, heat-labile, and sensitive to proteolysis. All of the activity bound to diethylaminoethyl (cellulose) and was eluted at 200 mM NaCl. The apparent molecular weight (by gel filtration) of the activity in extracts of uninjured brain was 9-17 kilodaltons, whereas the extracts of injured brain also had peaks or shoulders at 30, 70 and greater than or equal to 200 kilodaltons. These data suggest that the brain neurite-promoting activity resides in one or more proteins. Both the injury-induced and basal activities were different from laminin, nerve growth factor, and polyornithine-bindable neurite-promoting factors. The injury-induced activity was sensitive to repeated freezing and thawing, but this inactivation was reversed by thiol reagents such as glutathione, thioglycerol, and mercaptoethanol. We report a neurite-promoting factor that is induced following brain injury or denervation, and may also be important for reactive axon sprouting after brain injury. The induction of this factor is abnormal in aged animals, as is the reactive sprouting response. The properties of the injury-induced activity distinguish it from the basal activity (found in uninjured brain) and from other characterized neurite-promoting factors.