The effects of highly-selective blocker of γ-aminobutyric acid transporters of GAT1, NO-711, and substrate inhibitor of γ aminobutyric acid transporters GAT3, ß-alanine on the initial velocity of L-[14C]glutamate and [3H]-γ-aminobutyric acid uptake by cortical, hippocampal and thalamic nerve terminals (synaptosomes) were analyzed in norm and after perinatal hypoxia. Rats were underwent to hypoxia and seizures (airtight chamber, 4% O2 and 96% N2) at the age of 10–12 postnatal days. The experiments were performed at 8–9 weeks in the control and after hypoxia. It was shown that NO-711 (30 microM) and ß-alanine (100 microM) did not affect initial velocity of L-[14C] glutamate uptake by cortical, hippocampal and thalamic synaptosomes. In cortical synaptosomes, NO-711 and ß-alanine decreased the initial velocity of [3H]-γ-aminobutyric acid uptake, but their inhibitory effects were similar in control and hypoxia groups. The effectiveness of ß-alanine to influence [3H]-γ-aminobutyric acid uptake was increased in hippocampal and thalamic nerve terminals as a result of perinatal hypoxia, whereas the capacity of NO-711 in thalamic nerve terminals was decreased. These results suggest changes in the ratio of active GAT1/GAT3 expressed in the plasma membrane of nerve terminals after perinatal hypoxia. Thus, ß-alanine is a promising substance for development of neurotropic pharmacological preparations for the transporter-mediated regulation of GABA-ergic neurotransmission.

During inhalation, nano-/microsized particles of lunar dust are efficiently deposited in nasal, tracheobronchial, and alveolar regions and transported to the central nervous system. The neurotoxic potential of lunar dust has not yet been assessed. The research was focused on the analysis of the effects of lunar dust analogue on the key characteristics of glutamatergic neurotransmission. Disturbances in glutamate homeostasis contribute to the pathogenesis of major neurological disorders. The average size of particles of lunar dust analogue (JSC- 1a, Lunar Soil Simulant, Orbitec, USA) before and after sonication was determined by dynamic light scattering. With the use of radiolabeled L-[C-14]glutamate, it was shown that there is an increase in L-[C-14]glutamate binding to isolated rat brain nerve terminals (synaptosomes) in low [Nal media in the presence of lunar dust analogue that led to an apparent increase in the initial velocity of L-C-14 Iglutamate uptake by 10% in control rats, and those underwent to gravitational overload. Thus, the unique effect of lunar dust analogue to increase glutamate binding to the nerve terminals was shown. This can have deleterious effects on the extracellular glutamate homeostasis in the central nervous system that is extremely important for proper synaptic transmission. During a long-term mission, a combination of constant irritation due to dust particles, inflammation, stress, low gravity and microgravity, radiation, UV, and so on may consequently change the effects of the dust and aggravate neurological consequences.