|Main scientific achievements
- The results of the studies, conducted on the rats in the conditioned models with positive (model of alternative running) and negative (shuttle box) reinforcement, showed that during formation of memory trace serotonin-modulating anticonsolidation protein (SMAP; Mekhtiev, 2000) possesses negative regulatory activity. The studies showed that administration of SMAP into the brain lateral ventricle prior to learning sessions disrupted formation of memory traces in the shuttle box model (p<0.001; Guseinov, Mekhtiev, 2012; Mekhtiev et al., 2015). On the other hand, in the conditioned models of alternative running and instrumental differentiation intra-cerebral administration of anti-SMAP antibodies to the animals accelerated formation and improved quality (percent of correct trials) of memory traces were observed (p<0.001; Mekhtiev, Asadova, 2018).
- In the model of penicillin-induced seizures in the rabbits clonic convulsions and sharp upregulation of the amplitudes of the evoked potentials, induced by exposure to light flashes, in the colliculus superior and visual cortex were noticed. After 20-25 min from i.m. administration of SMAP cessation of clonic convulsions and return of the amplitudes of the evoked potentials to the pre-seizure values were recorded. The results give grounds to make a conclusion of downregulation of serotonergic system in pathogenesis of epileptic seizures (Mekhtiev et al., 2015).
- In the experiments, accomplished on grave form of retinitis pigmentosa in the rabbits, induced by i.v. administration of monoiod acetic acid, noticeable downregulation of rhodopsin and heat shock proteins 70 kDa (HSP70) in the retina and upregulation of SMAP in the hypothalamus (p<0.001) were revealed. Administration of SMAP into the corpus vitreous of the animals with induced retinitis pigmentosa leads to upregulation of rhodopsin and HSP70 (p<0.001; Ismailova, Mekhtiev, 2018). In the serum of the patients with diagnosed retinitis pigmentosa significant downregulation of natural anti-SMAP autoantibodies relatively to their level in the healthy persons (p<0.001) was revealed. In a whole, the obtained results give grounds to consider that in the patients with retinitis pigmentosa downregulation of serotonergic system in the hypothalamus occurs.
- The results of the studies, conducted on the fish, showed that under the effect of heavy metals and polyaromatic hydrocarbohydrates in the somatic cells sharp (5-fold) increase of the level of mutational changes (micronucleus test) was observed. I.m. administration of SMAP to the fish prior to their putting into the water with the above indicated pollutants led to decrease of the mutation level by over 50%. On the other hand, i.m. administration of anti-SMAP antibodies to the fish of the experimental group, kept in clean water, induced increase of the level of mutations relatively to their level in the animals, administered with non-immune γ-globulins (control for exclusion of side effects of antibodies).
- In the model of self-administration of morphine in the rats it was shown that in the cingulate cortex of the animals, reached stable level of drug addiction, upregulation of SMAP on 67% was noticed. Single i.m. administration of anti-SMAP antibodies to the animals that reached stable level of drug addiction, brought to decline of morphine consumption by 5-7 times. Such effect of suppression of drug addiction lasted for 8 days. The obtained results give grounds to make a conclusion on dual-way effect of anti-SMAP antibodies on drug addiction: on one hand, the antibodies block transduction of serotonin signal inside the nerve cells; on the other hand, they form negative memory trace on impossibility of formation of strong positive emotions after intake of morphine.
- With application of indirect ELISA-test the level of SMAP in the whole organism of the embryos of Xenopus laevis on different stages was evaluated. It was shown that from blastula stage to the ending of neurula stage the level of SMAP is left stable, whereas on the following stages its uninterruptable downregulation was observed. Addition of SMAP to the incubation medium of the embryos of Xenopus laevis on blastula stage leads to death of all embryos (Mekhtiev et al., 2016; Aminov, Mekhtiev, 2017).
- After addition of SMAP to the incubation medium of the embryos of both Lymneae stagnalis and Xenopus laevis on the stage of pre-metamorphosis acceleration of their development was observed. Particularly, on the background of upregulated SMAP level in the incubation medium, the embryos of Xenopus laevis passed through the stage of metamorphosis 2 stages earlier than the animals of the intact and control groups.
- The studies were conducted on the specimens of eastern bystryanka (Alburnoides bipunctatus eichwaldi), caught in the rivers running through the territory of Azerbaijan and having different levels of pollution. The results of the studies showed that in those cases, when SMAP is present in the animals’ tissues on enough high level, mechanisms of adaptation are launched in their organisms even towards high concentrations of highly toxic substances in the water (phenol at a concentration, 3 times exceeding upper adopted concentration). On the other hand, further increase of concentration of toxic substances in water leads to downregulation of SMAP in the animals’ tissues and exhaustion of protective resources, bringing finally to the processes of disadaptation (Mustafayev, Mekhtiev, 2014).
- The above mentioned results of the studies are confirmed by the results of the studies undertaken on the specimens of sazans. Particularly, under keeping of the specimens of sazan of the control group in the water, containing high concentration of insecticide actara, belonging to a group of neonicotinoids, for 5 days only 35% of specimens survived, whereas in the experimental group of animals, i.m. administered with SMAP and subjected to the effect of the same concentration of insecticide for 5 days, all animals survived (p<0.001; Allahverdiyeva, Mekhtiev, 2017). On the other hand, keeping the specimens of sazans of the control group in the water, containing sub-lethal dose of insecticide actara for 5 days did not cause death of a single specimen, while in the experimental group of animals i.m. administration of anti-SMAP antibodies with following keeping of the animals under the conditions and period of exposure, analogous to those of the control group, induced death of all specimens (p<0.001; Mekhtiev et al., 2017).