GABA's control of stem and cancer cell proliferation in adult neural and peripheral niches

Abstract

Aside from traditional neurotransmission and regulation of secretion, gamma-amino butyric acid (GABA) through GABA(A) receptors negatively regulates proliferation of pluripotent and neural stem cells in embryonic and adult tissue. There has also been evidence that GABAergic signaling and its control over proliferation is not only limited to the nervous system, but is widespread through peripheral organs containing adult stem cells. GABA has emerged as a tumor signaling molecule in the periphery that controls the proliferation of tumor cells and perhaps tumor stem cells. Here, we will discuss GABA's presence as a near-universal signal that may be altered in tumor cells resulting in modified mitotic activity.

FIGURE 1. Diagram of a human body

Diagram of a human body, including filled circles highlighting the CNS and peripheral organs displaying GABAergic signaling molecules. Dotted circles highlight changes in GABAergic components in certain tumors of the CNS and peripheral organs.

FIGURE 2. The brain and the subventricular zone

A: sagittal depiction of the brain and the subventricular zone (SVZ)-rostral migratory stream (RMS). B: a diagram of the adult SVZ. Ependymal (E) cells border the lateral ventricle (LV). Astrocytes (Astro) (neural stem/progenitor cells) surround a cluster of neuroblasts (N) and transit amplifying cells (T). Both astrocytes and neurob-lasts have GABA_A receptors, and astrocytes also have GABA transporters. C: structure of a portion of a hepatic lobule. D: diagram illustrating the parenchymal (hepatocyte) and nonparenchymal cells in the liver. Endothelial cells (EC) form the lining of the sinusoids (S). Kuffler cells (KC) are tissue macrophages. Stellate cells lie in the space between hepatocytes and endothelial cells. Arrows and asterisks indicate a classical and new definition of the perisinusoidal space of Disse between hepatocyte and stellate cells, respectively, and endothelial cells. GABA_A receptors are expressed in hepatocytes. E: diagram illustrating the different cells of the pancreas in the islet of Langerhans (endrocrine pancreas) and the acini (exocrine pancreas). F: diagram illustrating the location of pancreatic stellate cells. G: cross-section of the prostate. H: schematic of basal and luminal cells.