Manganese taken up into the CNS via the olfactory pathway in rats affects astrocytes

Manganese (Mn), administered intranasally in rats, is effectively taken up in the CNS via the olfactory system. In the present study, Mn (as MnCl2) di ssolved in physiological saline, was instilled intranasally in rats at dose s of 0 (control), 10, 250, or 1000 mu g. At the start of the experiment eac h rat received an intranasal instillation. Some rats were killed after one week without further treatment (the l-w group), whereas the remaining rats received further instillations after one and two weeks and were killed afte r an additional week (the 3-w group). The brains were removed and either us ed for ELISA-determination of the astrocytic proteins glial fibrillary acid ic protein (GFAP) and S-100b or histochemical staining of GFAP and S-100b, microglia (using an antibody against the iba1-protein) and the neuronal mar ker Fluoro-Jade. There were no indications that the Mn induced neuronal dam age. On the other hand, the ELISA showed that both GFAP and S-100b decrease d in the olfactory cortex, the hypothalamus, the thalamus, and the hippocam pus of the 3-w group. The only effect observed in the l-w group was a decre ase of S-100b in the olfactory cortex at the highest dose. The immunohistoc hemistry showed no noticeable reduction in the number of astrocytes. We ass ume that the decreased levels of GFAP and S-100b are due to an adverse effe ct of Mn on the astrocytes, although this effect does not result in astrocy tic demise. In the 3-w group, exposed to the highest dose of Mn, increased levels of GFAP and S-100b were observed in the olfactory bulbs, but these e ffects are probably secondary to a Mn-induced damage of the olfactory epith elium. Our results indicate that the astrocytes are the initial targets of Mn toxicity in the CNS.