PT  - JOURNAL ARTICLE
AU  - Bradford, Aaron B.
AU  - Mancini, Jayme D.
AU  - Atchison, William D.
TI  - Methylmercury-Dependent Increases in Fluo4 Fluorescence in Neonatal Rat Cerebellar Slices Depend on Granule Cell Migrational Stage and GABA<sub>A</sub> Receptor Modulation
AID  - 10.1124/jpet.115.226761
DP  - 2016 Jan 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 2--12
VI  - 356
IP  - 1
4099  - http://jpet.aspetjournals.org/content/356/1/2.short
4100  - http://jpet.aspetjournals.org/content/356/1/2.full
SO  - J Pharmacol Exp Ther2016 Jan 01; 356
AB  - Methylmercury (MeHg) disrupts cerebellar function, especially during development. Cerebellar granule cells (CGC), which are particularly susceptible to MeHg 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 fluo4 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 fluo4 fluorescence that depended on the stage of CGC development. CGCs in the EGL were most susceptible to MeHg-induced increases in fluo4 fluorescence. MeHg increased fluorescence in CGC processes but only diffusely; Purkinje cells rarely fluoresced in these slices. Neither muscimol nor bicuculline alone altered baseline fluo4 fluorescence in any CGC layer, but each delayed the onset and reduced the magnitude of effect of MeHg on fluo4 fluorescence in the EGL and ML. In the IGL, both muscimol and bicuculline delayed the onset of MeHg-induced increases in fluo4 fluorescence but did not affect fluorescence magnitude. Thus, acute exposure to MeHg causes developmental stage-dependent increases in Ca2+i 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 MeHg-induced Ca2+i dysregulation of CGCs.