Glutamate dependence of GABA levels in neurons of hypoxic and hypoglycemic rat hippocampal slices
Section snippets
Slice preparation
Transverse 400-μm sections of hippocampi were obtained from adult Sprague–Dawley rats and prepared as described in Madl and Burgesser.20 All experiments conformed to local and international guidelines on the ethical use of animals, and all efforts were made to minimize the number of animals used and their suffering. All slices were allowed to recover from the slicing process for 1 h at room temperature (about 23°C) in Hank's balanced salt solution (HBSS; 1.25 mM CaCl2, 0.7 mM MgSO4, 5.4 mM KCl, 0.4
Results
In control slices, GABA levels were reduced by 26±4.4% (n=8 slices) after 1 h of incubation from initial concentrations of 37±3.5 nmol/mg protein. The amount of GABA released into supernatants reached 9.4±0.3% of initial GABA levels after 1 h (n=4 slices). Blockade of GABA catabolism by GABA transaminase with 0.25 mM amino-oxyacetate (AOA) prevented normal decreases in GABA levels at 1 h (GABA levels=128±3.7% of control; n=4). The levels of GABA retained in slices in subsequent studies were
Discussion
Ischemia and post mortem incubations increase GABA levels in the CNS.9., 31. These increases may be due in part to increased activity of GAD during ATP depletion.22., 45. GAD activity also depends on glutamate concentrations. Glutamate acts as both a substrate for GAD and as a stimulator of GAD cycling from apoenzyme to holoenzyme.22 We have found that, in vitro, hypoglycemia reduces slice glutamate levels more than hypoxia at similar levels of ATP depletion.21 In the present study, we tested
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Cited by (36)
Sex and age differentially affect GABAergic neurons in the mouse prefrontal cortex and hippocampus following chronic intermittent hypoxia
2020, Experimental NeurologyCitation Excerpt :All results observed in the mPFC and hippocampus are summarized in Fig. 8. Previous studies have reported both increase (Madl and Royer, 2000; Pereira et al., 2017; Wood et al., 1968) and decrease (Yuan et al., 2015) in GABAergic neurons after hypoxia. In the context of conflicting evidence from published literature, the present study presents some interesting data showing the age- and sex-specific effects of CIH on GABAergic neurons and sub-populations in the hippocampus and mPFC, two brain regions critically involved in learning and memory.
Hypoxia and GABA shunt activation in the pathogenesis of Alzheimer's disease
2016, Neurochemistry InternationalCitation Excerpt :On the other hand, it is known that hypoxia robustly increases the levels of GABA in the brains of different animal species (Wood et al., 1968). Madl and Royer (2000) observed that the hypoxic response to elevated GABA levels appeared in neurons rather than glial cells in rat hippocampal slices, and GABA was most likely being synthesized from glutamate. Moreover, GABA can be generated from polyamines (Fig. 1).
Hippocampal GABAergic interneurons coexpressing alpha7-nicotinic receptors and connexin-36 are able to improve neuronal viability under oxygen-glucose deprivation
2015, Brain ResearchCitation Excerpt :Increased expression of GAD has been considered as a sign of GABAergic hyperactivity (Li et al., 2010). GAD-mediated GABA-synthesis is activated early after OGD and accompanied by enhanced mitochondria activity and synaptic GABA-release (Madl and Royer, 2000; Schwartz-Bloom and Sah, 2001; Jin et al., 2003; Ivannikov et al., 2013). These processes provide extracellular GABA-accumulation that, depending on ischemia conditions, contributes either to protection, as it was in our experiments in OGD-conditions, or to death of the pyramidal neurons.
In vivo effect of chronic hypoxia on the neurochemical profile of the developing rat hippocampus
2005, Developmental Brain Research