GABA increases Ca2+ in cerebellar granule cell precursors via depolarization: implications for proliferation.
The amino acids glutamate and gamma-aminobutyric acid (GABA) have primarily been characterized as the most prevalent excitatory and inhibitory, respectively, neurotransmitters in the vertebrate central nervous system. However, the role of these signaling molecules extends far beyond the synapse. GABA, glutamate, and their complement of receptors are essential signaling molecules that regulate developmental processes in both embryonic and young adult mammals. In this review, we describe the current knowledge on the role of GABA and glutamate in development, focusing on the perinatal cerebellum. We will then present novel data suggesting that GABA depolarizes granule cell precursors via GABA(A) receptors, which leads to calcium increases in these cells. Finally, we will consider the role of GABA and glutamate signaling on cell proliferation and perhaps neural cancers. From our review of the literature and these data, we hypothesize that GABA(A) receptors and metabotropic glutamate receptors may be a novel target for the pharmacological regulation of the cerebellar tumors, medulloblastomas.
Dave
Kathleen A
KA
Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06520-8082, USA.
Bordey
Angélique
A
D002118:Calcium / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002528:Cerebellar Neoplasms / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008527:Medulloblastoma / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
D011963:Receptors, GABA-A; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D002118:Calcium