Neuroprotective activation of astrocytes by methylmercury exposure in the inferior colliculus

Abstract

Methylmercury (MeHg) is well known to induce auditory disorders such as dysarthria. When we performed a global analysis on the brains of mice exposed to MeHg by magnetic resonance imaging, an increase in the T1 signal in the inferior colliculus (IC), which is localized in the auditory pathway, was observed. Therefore, the purpose of this study is to examine the pathophysiology and auditory dysfunction induced by MeHg, focusing on the IC. Measurement of the auditory brainstem response revealed increases in latency and decreases in threshold in the IC of mice exposed to MeHg for 4 weeks compared with vehicle mice. Incoordination in MeHg-exposed mice was noted after 6 weeks of exposure, indicating that IC dysfunction occurs earlier than incoordination. There was no change in the number of neurons or microglial activity, while the expression of glial fibrillary acidic protein, a marker for astrocytic activity, was elevated in the IC of MeHg-exposed mice after 4 weeks of exposure, indicating that astrogliosis occurs in the IC. Suppression of astrogliosis by treatment with fluorocitrate exacerbated the latency and threshold in the IC evaluated by the auditory brainstem response. Therefore, astrocytes in the IC are considered to play a protective role in the auditory pathway. Astrocytes exposed to MeHg increased the expression of brain-derived neurotrophic factor in the IC, suggesting that astrocytic brain-derived neurotrophic factor is a potent protectant in the IC. This study showed that astrogliosis in the IC could be an adaptive response to MeHg toxicity. The overall toxicity of MeHg might be determined on the basis of the balance between MeHg-mediated injury to neurons and protective responses from astrocytes.

Combining in vitro assays and mathematical modelling to study developmental neurotoxicity induced by chemical mixtures

“…Furthermore, rats acutely exposed to Methyl-Hg via oral administration, were found to undergo an increase of BDNF levels, which was linked to alteration of gut-brain axis related metabolites [ 80 ]. Increased expression of BDNF was found in astrocytes of the inferior colliculus (a brain region involved in auditory control) in Methyl-Hg-exposed mice [ 81 ]. Increased BDNF levels were also found in the cerebellum of adult male mice exposed for 2 weeks to 40 μg/mL Methyl-Hg (diluted in drinking water, ad libitum ), which also showed motor impairments characteristic of cerebellar toxicity [ 82 ].…”

Methylmercury induces neuronal cell death by inducing TNF-α expression through the ASK1/p38 signaling pathway in microglia

“…reported that methylmercury-induced interleukin-6 (IL-6) expression in astrocytes suppresses methylmercury-induced neuronal cell death 15 , 16 . Induction of methylmercury-induced IL-6 expression in the astrocytes in the midbrain of mice has been shown to be protective against methylmercury-induced hearing impairment 17 . Furthermore, we found that methylmercury-induced expression of the chemokine CCL4 in the mouse brain suppresses neuronal damage 18 .…”

MicroRNA‑206 relieves irradiation‑induced neuroinflammation by regulating connexin 43

“…Astrocytes, the most abundant cell type in the CNS, are functionally and structurally associated with numerous pathological responses to disease ( 32 ). It has also been reported that astrocytes aggravated ischemic stroke injury; however, they also exert neuroprotective effects by releasing neurotrophic proteins ( 33 , 34 ). At present, certain astrocyte-based neuroprotective treatment strategies include treatment for astrocyte protection ( 35 ), astrocyte anti-excitotoxicity and antioxidation ( 36 ), as well as astrocyte-derived growth factors ( 37 ).…”