Influence of glutamate and GABA transport on brain excitatory/inhibitory balance

2021 ◽  
pp. 153537022198926
Author(s):  
Sheila MS Sears ◽  
Sandra J Hewett

An optimally functional brain requires both excitatory and inhibitory inputs that are regulated and balanced. A perturbation in the excitatory/inhibitory balance—as is the case in some neurological disorders/diseases (e.g. traumatic brain injury Alzheimer’s disease, stroke, epilepsy and substance abuse) and disorders of development (e.g. schizophrenia, Rhett syndrome and autism spectrum disorder)—leads to dysfunctional signaling, which can result in impaired cognitive and motor function, if not frank neuronal injury. At the cellular level, transmission of glutamate and GABA, the principle excitatory and inhibitory neurotransmitters in the central nervous system control excitatory/inhibitory balance. Herein, we review the synthesis, release, and signaling of GABA and glutamate followed by a focused discussion on the importance of their transport systems to the maintenance of excitatory/inhibitory balance.

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 566
Author(s):  
Jae-Geun Lee ◽  
Hyun-Ju Cho ◽  
Yun-Mi Jeong ◽  
Jeong-Soo Lee

The microbiota–gut–brain axis (MGBA) is a bidirectional signaling pathway mediating the interaction of the microbiota, the intestine, and the central nervous system. While the MGBA plays a pivotal role in normal development and physiology of the nervous and gastrointestinal system of the host, its dysfunction has been strongly implicated in neurological disorders, where intestinal dysbiosis and derived metabolites cause barrier permeability defects and elicit local inflammation of the gastrointestinal tract, concomitant with increased pro-inflammatory cytokines, mobilization and infiltration of immune cells into the brain, and the dysregulated activation of the vagus nerve, culminating in neuroinflammation and neuronal dysfunction of the brain and behavioral abnormalities. In this topical review, we summarize recent findings in human and animal models regarding the roles of the MGBA in physiological and neuropathological conditions, and discuss the molecular, genetic, and neurobehavioral characteristics of zebrafish as an animal model to study the MGBA. The exploitation of zebrafish as an amenable genetic model combined with in vivo imaging capabilities and gnotobiotic approaches at the whole organism level may reveal novel mechanistic insights into microbiota–gut–brain interactions, especially in the context of neurological disorders such as autism spectrum disorder and Alzheimer’s disease.


SIMULATION ◽  
2003 ◽  
Vol 79 (11) ◽  
pp. 648-669 ◽  
Author(s):  
Angela Nebot ◽  
Francisco Mugica ◽  
François E. Cellier ◽  
Montserrat Vallverdú

1993 ◽  
Vol 265 (5) ◽  
pp. R1212-R1215 ◽  
Author(s):  
W. K. Samson ◽  
T. C. Murphy

The receptor subtype mediating the antidipsogenic effects of the endothelins (ETs) was determined in conscious, unrestrained, normally hydrated rats. Intracerebroventricular injection of 6, 12, and 20 ng ET-2 resulted in a significant, dose-related inhibition of water drinking in response to subsequent injection of 100 pmol angiotensin II (ANG II). Pretreatment with 50 or 100 ng ET-B receptor agonist failed to alter the subsequent drinking response to ANG II. Drinking in response to ANG II was significantly accentuated in rats pretreated with 50, 100, and 200 ng of the selective ET-A receptor antagonist BQ-123. These data indicate that the antidipsogenic effects of the ETs are mediated via the ET-A receptor subtype and further suggest that endogenous ET plays a physiologically relevant role in the central nervous system control of fluid and electrolyte homeostasis.


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