Abstract
Because of their ability to modulate the Gamma Aminobutyric Acid (GABA) a receptor complex, the principal aim of the current work is to assess two essential heavy metals: Iron (Fe) and zinc (Zn) by atomic absorption in different brain areas of stressed rat s. To do so, we investigated the effect of acute immobilization stress (single 1-hour session) on th e distribution and the densities of GABA A receptors as well as the concentrations of Zn and Fe in several rat brain regions of the stressed rats. Animals wer e randomly assigned to either control or stress condi tions and changes in specific binding of the GABA A receptor as labelled with T-Butylbicyclophosphonothionate (TBPS) (ligand useful for GABA A receptor) were assessed by in vitro quantitative autoradiogra phy with the aid of a computer-assisted image analy sis system whereas the assessment of Fe and Zn concentrations was done by atomic absorption spectrophotometry. Exposure to 1h immobilization stress led to a significant increase in [ 35 S]-TBPS binding site density in stressed rats compared to controls (30-40% increase in cortex, hypothalamus, hippocampus and substatntia nigra). In the other analyzed brain structures, specific binding of [ 35 S]-TBPS remained unchanged in stressed rats. The spectrophotometer a nalysis showed significant decrease in Zn levels in the whole forebrain structures as well as the mesenceph alon of stressed rats. The striking differences are noticed in hippocampus and mesencephalon. Furthermore, Fe endogenous concentrations display similar pattern following stress. The present study demonst rates that immobilization stress induces an increas e in GABA A receptors concomitant to a reduction of Zn and Fe c ontent in the stress sensitive rat brain structures . Besides supporting the alteration of the modulatory function occurring at the GABA A receptor level after stress, our data also reveal that the measured brai n concentrations of the investigated heavy metals r emain not sufficient to efficiently modulate the activity of with efficacy such complex receptor. This could explain the higher densities of GABA A receptors observed after acute stress.
Highlights
Gamma Aminobutyric Acid (GABA) A receptors are ligand-gated ion channels, mediating fast synaptic inhibition in the Central Nervous System (CNS) (Mody, 2012; Farrant and Nusser, 2005)
The other structures belonging to cerebral cortex, thalamus and hypothaIamus did not display any significant differences in TBPS binding
The present study examined the effects of immobilization stress on the brain concentrations of two essential heavy metals, i.e., zinc and iron, i.e., zinc and iron proposed as endogenous modulators of the GABAA receptor complex
Summary
Gamma Aminobutyric Acid (GABA) A receptors are ligand-gated ion channels, mediating fast synaptic inhibition in the Central Nervous System (CNS) (Mody, 2012; Farrant and Nusser, 2005). These receptors are the targets of a variety of pharmacologically and clinically important drugs such as benzodiazepines, depressant barbiturates and neuroactive steroids (Smith et al, 2007). Beside these major modulators, some metal cations are able to inhibit the GABA response of neurons in a variety of organisms (Chen and Yung, 2006). Box: 523, Sultan Moulay Slimane University, Béni-Mellal 23000, Morocco Tel: 212-523485112 Fax: 212-523485201
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