Back to Search
Start Over
Rescue of neuronal migration deficits in a mouse model of fetal Minamata disease by increasing neuronal Ca2+ spike frequency.
- Source :
- Proceedings of the National Academy of Sciences of the United States of America; 3/27/2012, Vol. 109 Issue 13, p5057-5062, 6p
- Publication Year :
- 2012
-
Abstract
- In the brains of patients with fetal Minamata disease (FMD), which is caused by exposure to methylmercury (MeHg) during development, many neurons are hypoplastic, ectopic, and disoriented, indicating disrupted migration, maturation, and growth. MeHg affects a myriad of signaling molecules, but little is known about which signals are primary targets for MeHg-induced deficits in neuronal development. In this study, using a mouse model of FMD, we examined how MeHg affects the migration of cerebellar granule cells during early postnatal development. The cerebellum is one of the most susceptible brain regions to MeHg exposure, and profound loss of cerebellar granule cells is detected in the brains of patients with FMD. We show that MeHg inhibits granule cell migration by reducing the frequency of somal Ca<superscript>2+</superscript> spikes through alterations in Ca<superscript>2+</superscript>, cAMP, and insulin-like growth factor 1 (IGF1) signaling. First, MeHg slows the speed of granule cell migration in a dose-dependent manner, independent of the mode of migration. Second, MeHg reduces the frequency of spontaneous Ca<superscript>2+</superscript> spikes in granule cell somata in a dose-dependent manner. Third, a unique in vivo live-imaging system for cell migration reveals that reducing the inhibitory effects of MeHg on somal Ca<superscript>2+</superscript> spike frequency by stimulating internal Ca<superscript>2+</superscript> release and <superscript>2+</superscript> influxes, inhibiting cAMP activity, or activating IGF1 receptors ameliorates the inhibitory effects of MeHg on granule cell migration. These results suggest that alteration of Ca<superscript>2+</superscript> spike frequency and Ca<superscript>2+</superscript>, cAMP, and IGF1 signaling could be potential therapeutic targets for infants with MeHg intoxication. [ABSTRACT FROM AUTHOR]
- Subjects :
- MERCURY poisoning
GROWTH factors
NEURAL transmission
METHYLMERCURY
CELL migration
Subjects
Details
- Language :
- English
- ISSN :
- 00278424
- Volume :
- 109
- Issue :
- 13
- Database :
- Complementary Index
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 74025438
- Full Text :
- https://doi.org/10.1073/pnas.1120747109