No abstract

The expression of the glial fibrillary acidic protein (GFAP), a component of astroglial intermediate filaments, is regulated under developmental and pathological conditions. In order to characterize DNA sequences involved in such regulations, we produced transgenic mice bearing 2 kb of the 5' flanking region of the murine GFAP gene linked to the Escherichia coli beta-galactosidase (beta-gal) reporter gene. Seven transgenic lines were obtained. We observed that the regulatory elements present in the transgene GFAP-nls-LacZ direct an expression in the neural and non-neural tissue and target in vivo an unexpected subpopulation of astrocyte. In the developing brain, beta-gal activity and GFAP appeared simultaneously and in the same region, on embryonic day 18 (E18), suggesting that the 2 kb of the promoter contains the regulatory sequences responsible for the perinatal vimentin/GFAP switch. In addition, we demonstrated that the 2 kb sequence of the GFAP promoter used in the transgene possess elements which are activated after a surgical injury, thus permitting to study some aspects of reactive gliosis in these transgenic mice. These transgenic lines provide a useful tool by enabling further studies of astroglial and, probably, neuronal physiologies.

No abstract

The cytokine tumor necrosis factor‐α (TNFα) has been proposed to play a key role in the degenerative processes observed in demyelinating diseases such as multiple sclerosis (MS). In the immune system the cellular responses to TNF are mediated by two different receptors: TNF‐RI, which is involved in cell death, and TNF‐RII, which has been shown to mediate cell proliferation. We investigated the oligodendroglial expression of TNF‐RI and ‐RII. In vivo, in normal adult rodent brain, oligodendrocytes express TNF‐RII but not TNF‐RI. However, after 3 days in culture, both types of receptors were expressed by mature oligodendrocytes, purified from 4‐week‐old rats, suggesting that expression of TNF‐RI was induced by either the isolation process or the culture conditions. This inducibility of TNF‐RI may explain the differences in oligodendrocyte cell death reported in various experimental conditions and in the pathology of MS lesions.

In previous studies, we have shown that a traumatic lesion to the hippocampus of adult mice induces the transitory expression of TNF alpha and IL-1 alpha by neurons of different brain areas and also by glial cells at the site of injury. The aim of the present study was to establish whether the expression of TNF alpha and IL-1 alpha is restricted to defined subpopulations, or else is common to most of the central neuronal populations. Using polyclonal anti-GAD 67, anti-TH and monoclonal anti-ChAT, and anti-5-HT antibodies in a double-labeling immunohistochemical procedure in combination with murine anti-TNF alpha and anti-IL-1 alpha polyclonal antibodies, we show that most GABAergic, catecholaminergic, and serotoninergic neurons, and a subgroup of the cholinergic neurons, express these cytokines. Although not immunohistochemically characterized, neurons in some glutamatergic structures such as the hippocampus and the prefrontal cortex also express these cytokines. Thus, we conclude that the capacity of central neurons to express cytokines like TNF alpha and IL-1 alpha in reaction to a brain injury is not restricted to peculiar neuronal subtypes, but could include most of the neuronal populations of the brain.