PT  - JOURNAL ARTICLE
AU  - Bradford, Aaron B.
AU  - Mancini, Jayme D.
AU  - Atchison, William D.
TI  - METHYLMERCURY-ASSOCIATED INCREASES IN FLUO4 FLUORESCENCE IN NEONATAL RAT CEREBELLAR SLICES ARE DEPENDENT ON GRANULE CELL MIGRATIONAL STAGE AND MODULATED BY GABA<sub>A</sub> RECEPTORS.
AID  - 10.1124/jpet.115.226761
DP  - 2015 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - jpet.115.226761
4099  - http://jpet.aspetjournals.org/content/early/2015/10/29/jpet.115.226761.short
4100  - http://jpet.aspetjournals.org/content/early/2015/10/29/jpet.115.226761.full
AB  - Methylmercury (MeHg) disrupts cerebellar function, especially during development. Cerebellar granule cell (CGC) cells, which are particularly susceptible to MeHg, but by unknown mechanisms, migrate during this process. Transient changes in intracellular Ca2+(Ca2+i) are crucial to proper migration, and MeHg is well known to disrupt CGC Ca2+i regulation. Acutely prepared slices of neonatal rat cerebellum, in conjunction with confocal microscopy and fluo-4 epifluorescence were used to track changes induced by MeHg in CGC Ca2+i regulation in the external (EGL) and internal granule cell layers (IGL) as well as the molecular layer (ML). MeHg caused no cytotoxicity, but did cause a time-dependent increase in fluo-4 fluorescence that depended on the stage of granule cell development. CGCs in the EGL were most susceptible to MeHg-induced increases in fluo-4 fluorescence. MeHg increased fluorescence in CGC processes, but only diffusely; Purkinje cells rarely fluoresced in these slices. Neither muscimol nor bicuculline alone altered baseline fluo-4 fluorescence in any CGC layer, but each delayed the onset and reduced the magnitude of effect of MeHg on fluo-4 fluorescence in the EGL and ML. In the IGL, both muscimol and bicuculline delayed the onset of MeHg-induced increases in fluo-4 fluorescence, but didn't affect fluorescence magnitude. Thus acute exposure to MeHg causes developmental stage-dependent increases in divalent cation concentrations in CGCs. Effects are most prominent in CGCs during development, or early stages of migration. GABAA receptors participate in an as yet unclear manner to dysregulation by MeHg of CGC Ca2+i.