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Manganese taken up into the CNS via the olfactory pathway in rats affects astrocytes
1Department of Pharmacology and Toxicology, Faculty of Veterinary Medicine, Swedish University of Agricultural Sciences, Uppsala. jorgen.henriksson@farmtox.slu.se
Abstract:
Manganese (Mn), administered intranasally in rats, is effectively taken up in the CNS via the olfactory system. In the present study, Mn (as MnCl(2)) dissolved in physiological saline, was instilled intranasally in rats at doses of 0 (control), 10, 250, or 1000 microg. At the start of the experiment each rat received an intranasal instillation. Some rats were killed after one week without further treatment (the 1-w group), whereas the remaining rats received further instillations after one and two weeks and were killed after an additional week (the 3-w group). The brains were removed and either used for ELISA-determination of the astrocytic proteins glial fibrillary acidic protein (GFAP) and S-100b or histochemical staining of GFAP and S-100b, microglia (using an antibody against the iba1-protein) and the neuronal marker Fluoro-Jade. There were no indications that the Mn induced neuronal damage. On the other hand, the ELISA showed that both GFAP and S-100b decreased in the olfactory cortex, the hypothalamus, the thalamus, and the hippocampus of the 3-w group. The only effect observed in the 1-w group was a decrease of S-100b in the olfactory cortex at the highest dose. The immunohistochemistry showed no noticeable reduction in the number of astrocytes. We assume that the decreased levels of GFAP and S-100b are due to an adverse effect of Mn on the astrocytes, although this effect does not result in astrocytic 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 effects are probably secondary to a Mn-induced damage of the olfactory epithelium. Our results indicate that the astrocytes are the initial targets of Mn toxicity in the CNS.
Insights
Intranasal manganese exposure in rats affects astrocytes in the central nervous system (CNS). While not causing neuronal damage, manganese alters astrocytic proteins, indicating astrocytes as initial targets of manganese toxicity.
Area of Science:
- Neurotoxicology
- Environmental Health
- Cell Biology
Background:
- Manganese (Mn) uptake into the central nervous system (CNS) occurs via the olfactory system following intranasal administration.
- Astrocytes play crucial roles in CNS function and are potential targets for neurotoxicants.
- Understanding Mn's effects on astrocytes is vital for assessing neurotoxic risks.
Purpose of the Study:
- To investigate the effects of intranasally administered manganese chloride (MnCl2) on astrocytes in the rat brain.
- To determine if Mn exposure induces neuronal damage or alters astrocytic protein levels (GFAP, S-100b).
- To identify the primary cellular targets of Mn toxicity in the CNS.
Main Methods:
- Rats received intranasal instillations of MnCl2 at doses of 0, 10, 250, or 1000 µg.
- Brain tissues were analyzed after 1 week (1-w group) or 3 weeks (3-w group) using ELISA and immunohistochemistry.
- Evaluated GFAP, S-100b (astrocytic markers), iba1 (microglia marker), and Fluoro-Jade (neuronal damage marker).
Main Results:
- No evidence of Mn-induced neuronal damage was observed.
- ELISA revealed decreased GFAP and S-100b levels in multiple brain regions (olfactory cortex, hypothalamus, thalamus, hippocampus) in the 3-w group.
- Increased GFAP and S-100b were noted in olfactory bulbs in the 3-w high-dose group, potentially secondary to olfactory epithelium damage.
Conclusions:
- Intranasal Mn exposure adversely affects astrocytes, evidenced by altered GFAP and S-100b levels, without causing cell death.
- Astrocytes appear to be the initial targets of Mn toxicity within the CNS.
- Further research is needed to elucidate the mechanisms of Mn-induced astrocytic alterations and their functional consequences.