ИСТИНА

For decades the goal of biomedical researches was to find a multipurpose animal model for development treatment for neurobiological diseases. Bioethical communities’ requirements are growing rapidly what makes scientists all over the world to follow the 3R concept (Refinment, Reduction, Replacement). Comparative physiology methods proved the possibility of using Paramecium caudatum in preclinical studies. This animal model was called ‘a moving neuron’. Electrophysiology: Paramecium’s swimming behavior directly depends on the membrane potential. Сell’s membrane resting potential will be within -30 mV; that is a little bit different from other animals cells resting potentials. The Paramecium caudatum membrane has all necessary channels: K, Ca, Cl, etc. These channels are going to act as conductors with non-zero resistance; the lipid membrane is going to take capacitor properties (accumulate charge). Researches demonstrate ciliates ionic conductivity that directly controls its movement. The ability to observe the response of a whole cell to a given stimulus, and to register this response, makes paramecium a very effective observation model that exposed to pharmacological substances [1]. Biochemistry: Like a mammalian neuron, paramecium caudatum can produce into the environmental mediators that are very similar in structure and functions to higher animals brain mediators such as serotonin, dopamine, norepinephrine, GABA and glutamate. Biogenic monoamines regulate the process of a cell division, glucose metabolism, cilia regeneration and phagocytosis, as well as controlling the flow of cilia during swimming by changing the potential. This model can become the basis for fundamental researches on the mechanisms of mediators transport at the cellular and molecular levels [2]. Cytology: Immunohistochemical method showed that receptors for secreted mediators are located on the surface of the paramecium membrane but no binding sites for dopamine were found. The abundant secretion of dopamine is due to the synthesis of norepinephrine from dopamine. Norepinephrine is very important for the life of ciliates. Activation of norepinephrine receptors stimulates eating behavior of paramecia [3]. The structure of the Protozoa includes different types of opiate receptors. The subtype of the µ-opiate receptor in paramecium caudatum is defined as a receptor with a high percentage (about 95%) identity to a human neuronal mu-opiate receptor. Activation of these receptors leads to a cell aggregation; such a cellular response allows making psychopharmacological studies on paramecium caudatum [4]. The unique structure of paramecium, as well as its ability to respond to a stimulus according to a primitive behavioral program, allows this entity to be a preclinical animal model in the study of nootropics, antioxidants, cytoprotectors and other drugs, that can restore impaired function of channels and receptors. The cultivation of paramecium allows to get a large number of clones, which improves the quality of the development and makes a large statistical sample; the cheap and mobile keeping of a colony makes comfortable conditions for researches. References [1] Schlaepfer C.H., Wessel R. Excitable Membranes and Action Potentials in Paramecia: An Analysis of the Electrophysiology of Ciliates. // Journal of undergraduate neuroscience education: JUNE: a publication of FUN, Faculty for Undergraduate Neuroscience. 2015. № 1 (14), A82-86. [2] Ramoino P., Candiani S., Pittaluga A., Usai C., Gallus L., Ferrando S., Milanese M., Faimali M., Bonanno G. Pharmacological characterization of NMDA-like receptors in the single-celled organism Paramecium primaurelia. // The Journal of experimental biology. 2014. № Pt 3 (217), 463–471. [3] Gundersen R.E., Thompson G.A. Further Studies of Dopamine Metabolism and Function in Tetrahymena 1 // The Journal of Protozoology. 1985. № 1 (32), 25–31. [4] Shahrokhi S.S., Kesmati M., Kazemi B. Interaction of nicotine with morphine potency in Paramecium caudatum // Heliyon. 2019. № 8 (5).