[Cellular regulation of the lower urinary tract as a cause of the bladder overactivity and reduced efficiency of pharmacotherapy].

Overactive bladder (OAB) is a polyetiological nosology. Its symptoms are often characterized not only with detrusor hyperactivity, but also with the increased sensitivity of afferent fibers, which is clinically manifested as urgency. In addition, the disorders at the level of receptors expression and the synthesis of mediators lead to the development of bladder pain syndrome (BPS), which also significantly reduces the quality of life of patients. In recent years, the experimental animal studies achieved significant progress in understanding of the pathogenesis of lower urinary tract dysfunction. In particular, the broad understanding of the sensor properties of urothelium was obtained, which significantly increased the popularity of the urothelial theory of the development of idiopathic detrusor hyperactivity, as well as hypersensitivity and bladder pain. According to this theory, the pathological release of biologically active substance in the transitional epithelium in response to an extension of the bladder wall leads to clinical manifestations of the described conditions. In addition, due to the studies of the properties of receptors, ion channels, and mediators, the suggestion about the reduced efficiency of muscarinic receptor antagonists have been made in a large number of patients. Besides the acetylcholine control of the lower urinary tract, more and more attention is paid to other significant mechanisms of pathological conditions. The purpose of this part of the lecture is to systematize the available materials of basic research on the functioning of the lower urinary tract at the cellular level, as well as the mechanisms of action and questions of the effectiveness of pharmacological therapy for urinary disorders.

[Characteristics of the neural regulation of the lower urinary tract as a cause of the development of an overactive bladder: current state of the problem].

An overactive bladder (OAB) is a constellation of lower urinary tract symptoms, including urgency, increased frequency of urination during the day and/or night (nocturia), and, in some cases, urge incontinence. This syndrome can be caused by different conditions, and currently no universal pathogenetic treatment has been developed. In addition, there are virtually no Russian-language publications providing information on the neurophysiology and neuroanatomy of the lower urinary tract. At the same time, the importance of this topic can hardly be overestimated. Often, a patient with a neurogenic dysfunction of the lower urinary tract has different comorbidities, which requires to deeply understand the mechanisms of development of certain symptoms. Considering an absence of clear data about the peripheral bladder innervation, role of the structures of the central nervous system and importance of neurotransmitters, it is rather difficult to provide high-quality specialized care. However, in recent years, a lot of new facts and theories have been described in basic researches. This lecture is dedicated to the current data on the pathogenesis of OAB. The purpose of the lecture is to summarize the results of fundamental and clinical studies on the pathogenesis of OAB.

[ELECTRICAL ACTIVITY OF THE NEOCORTEX IN ADULT RATS AFTER PRENATAL HYPOXIA AND IN EPILEPSY MODEL].

Changes in electrical activity of neocortex after prenatal hypoxia (day 14 of embryogenesis - E14, 7 % 02 for 3 hours) and these combined with intracortical microinjection of epileptogenic 4-aminopyridine (4-AP) have been studied in adult rats. We analyzed the frequency-time parameters of electrocorticogram (ECoG) during sleep and wakefulness as well as spike-wave discharge (SWD) in 4-AP-induced epileptiform model. The results showed that in rats subjected to prenatal hypoxia the theta rhythm had a lower frequency and sleep spindles were characterized by lower spectral power in low-frequency domain in comparison with the control group. In rats with prenatal pathology delayed onset of epileptiform activi- ty and altered frequency distribution of the spectral power of 4-AP-induced SWD were revealed.

Delayed effect of prenatal exposure to hypoxia on the susceptibility of rats to electric seizures.

We studied the delayed effects of prenatal exposure to hypoxia on the susceptibility of rats to seizures. The later was estimated using graded electroshock. The experiments were performed in two groups of 1.5-year-old male Wistar rats. The experimental group consisted of the animals that were exposed to hypoxia on day 14 of prenatal development, and the control group consisted of the animals that developed under the normal conditions. In the rats subjected to prenatal hypoxia, seizure episodes induced by weak currents in the range of 10-40 mA and their average duration were more pronounced as compared to the control animals.

Role of the trace amine associated receptor 5 (TAAR5) in the sensorimotor functions.

Classical monoamines are well-known modulators of sensorimotor neural networks. However, the role of trace amines and their receptors in sensorimotor function remains unexplored. Using trace amine-associated receptor 5 knockout (TAAR5-KO) mice, that express beta-galactosidase mapping its localization, we observed TAAR5 expression in the Purkinje cells of the cerebellum and the medial vestibular nucleus, suggesting that TAAR5 might be involved in the vestibular and motor control. Accordingly, in various behavioral tests, TAAR5-KO mice demonstrated lower endurance, but better coordination and balance compared to wild-type controls. Furthermore, we found specific changes in striatal local field potentials and motor cortex electrocorticogram, such as a decrease in delta and an increase in theta oscillations of power spectra, respectively. The obtained data indicate that TAAR5 plays a considerable role in regulation postural stability, muscle force, balance, and motor coordination during active movements, likely via modulation of monoaminergic systems at different levels of sensorimotor control involving critical brain areas such as the brainstem, cerebellum, and forebrain.