Astrocytes express both GABA ARs and GABA BRs in the soma, the synapse-surrounding processes, and the brain vessel-contacting endfeet (Nilsson et al., 1993 Charles et al., 2003 Meier et al., 2008).
Astrocytes are also with GABA uptake capacity which requires at least two sodium ions per transportable GABA molecule ( Figure 1 Larsson et al., 1980). GABA is the main inhibitory transmitter in adults, which binds to GABA receptors (ionotropic GABA A receptors, GABA ARs and metabotropic GABA B receptors, GABA BRs) on neurons and inhibits neuronal activities via reducing exocytosis, hyperpolarizing membranes, and shunting depolarization. Astrocytes also contain a considerable amount of GABA that can be released to modulate the activities of GABA receptors-expressing cells, indicating a GABAergic role of astrocytes (Le Meur et al., 2012 Yoon et al., 2012).Īstrocytes Internalize GABA via GABA Receptors and Transporters Astrocytes express GABA receptors to interact with an extracellular GABA, suggesting astrocytes as GABAceptive cells (Le Meur et al., 2012 Yoon et al., 2012). In the recent decade, gamma-aminobutyric acid (GABA) has emerged as a novel gliotransmitter (Yoon and Lee, 2014). More importantly, astrocytes directly regulate synaptic plasticity and synaptic transmission by releasing gliotransmitters such as glutamate, adenosine triphosphate (ATP), taurine, glycine, and D-serine (Barakat and Bordey, 2002 Hussy, 2002 Henneberger et al., 2010 Bernardinelli et al., 2014 Mederos and Perea, 2019). Astrocytes induce synaptic formation, regulate the release and uptake of synaptic neurotransmitters, and maintain synaptic cleft transmitter homeostasis (Allen, 2014). They form complex connections with neurons, blood vessels, and other glial cells, and play an important role in preserving normal brain functions via providing energy and nutritional support for neurons, maintaining metabolic homeostasis of the CNS, and regulating cerebral blood flow (Anderson and Nedergaard, 2003 Bélanger et al., 2011 Scheiber and Dringen, 2013).Ī single astrocyte can touch more than 100,000 synapses in the mouse cortex via a tripartite synapse, a structure that the astrocyte associates with the pre- and post-synapse areas of neurons (Bushong et al., 2002).
#ZMATRIX AND GABA TRIAL#
The clinical trial registry number is NCT04086108 ().Astrocytes, the most abundant glial cells in the central nervous system (CNS), account for about 20% of the glial cells in the neocortex of the human brain (Pelvig et al., 2008). The results merit further studies on the bioavailability of GABA from other food products and the health effects of GABA-rich diets.
These data suggest that GABA is bioavailable from tomatoes, and that food products containing GABA could potentially induce health effects similar to those claimed for GABA supplements. For glutamate, the absorption from pureed tomatoes occurred more slowly as seen from a longer t max (0.98 ± 0.14 h vs. GABA from pureed tomatoes showed similar bioavailability to that of a solution in water. Fasting GABA levels were constant (5.8 CV%) between individuals, while fasting glutamate levels varied considerably (23.5 CV%). Fasting plasma GABA and glutamate concentrations were found to be 16.71 (SD 2.18) ng mL - (SD 1666) ng mL -1, respectively. Plasma GABA and glutamate concentrations were determined by ultra-pressure liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS). Following intake, 18 blood samples were taken at intervals for 24 hours. The drinks were a solution of 888 mg L -1 GABA, a solution of 3673 mg L -1 glutamate, pureed fresh tomatoes and plain water as the control. After a fasting blood sample was taken, eleven healthy men randomly received 1 liter of 4 different drinks in a cross-over design with a one-week interval. We studied the bioavailability of GABA and glutamate from tomatoes relative to a solution in water. However, the bioavailability from food remains unknown. Recent studies in rodents suggest beneficial effects of oral GABA on glucose homeostasis and blood pressure. Besides endogenous production, both compounds are found in food products, reaching relatively high levels in tomatoes. Both function as neurotransmitters in the central nervous system, but they also modulate pancreatic and immune functioning, for example. Gamma-aminobutyric acid (GABA) and its precursor glutamate play signaling roles in a range of tissues.
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