Vol 41, No 2 (2024)

Glycoprotein N-cadherin (Neuronal cadherin) belongs to the family of calcium-dependent cell adhesion molecules, representing a key element that carries out intercellular contacts in brain neurons. However, it is involved not only in the mechanical connection of neurons, but also influences the specifics of the further development and functional state of the neuron. This is due to the active interaction of N-cadherin with many proteins at the pre- and post-synapse, initiating a cascade of reactions that provide such processes as long-term potentiation (underlying learning and memory), morphogenesis, neuronal recognition, activation of receptors (NMDA and AMPA types), regulation of cytoskeleton formation. This polyfunctionality is necessary for specific neurons to connect to each other in a certain way, and such adhesion leads to the coordination of cell behavior through intercellular signaling and spatio–temporal control of differential gene expression. Mutations in the genes responsible for the expression of N-cadherin lead to various disorders of the functional activity of the synapse and the processes of spatial orientation and memory. Thus, involvement in important neuroplastic processes regulating cognitive functions and behavior determines interest in studying the effect of drugs on N-cadherin. In particular, N-cadherin deserves closer consideration by pharmacologists as a potential target in the mechanism of action of various psychoactive substances.

A possible mechanism is proposed for the influence of oxytocin and vasopressin on the functioning of the neural network in the CNS, in which olfactory information is processed and stored, and which plays an important role in social behavior. The effect of these neuropeptides on postsynaptic receptors associated with Gq/11 proteins contributes to the induction of LTP of the efficacy of excitatory synaptic inputs to the main projection cells and to inhibitory interneurons in the prefrontal cortex, hippocampus, piriform cortex, anterior olfactory nucleus, olfactory bulb and nucleus accumbens, including the olfactory tubercle. As a result of disynaptic inhibition in each of the structures, the signal-to-noise ratio is improved and the transmission of strong signals through projection neurons to their target cells is facilitated. Due to the fact, that oxytocin promotes the release of dopamine by the neurons of the ventral tegmental area, the conditions for processing and memorizing olfactory information in the interconnected olfactory and hippocampal neural networks, including cortical and subcortical structures, are improved, and attention is also included in this processing. Long-term modification of the effectiveness of interneuronal connections in these networks under the influence of oxytocin and dopamine contributes to the formation and stabilization of contrasting neuronal representation of odors formed in cortical areas. Orientation of attention increases the significance of socially important olfactory stimuli and improves the conditions for the functioning of the reinforcement system necessary for adequate social behavior. Taking into account the known data on the correlation between social behavior and the density of oxytocin and vasopressin receptors on neurons of different structures, understanding the mechanisms of the influence of these neuropeptides on the functioning of the olfactory system can be useful for finding ways to correct behavior if necessary.

Two periods of autophagy activation, differently significant for the development of resistance, were demonstrated in the model of neuronal resistance to the toxic effect of glutamate (deprivation of trophic factors). The autophagy inhibitor 3-methyladenine (3-MA) at a concentration of 1.25 mM significantly suppresses resistance development, but only if applied immediately after deprivation of trophic factors. Inhibition of autophagy with 3-MA immediately during deprivation does not affect resistance production. In addition, activation of autophagy is responsible for the decrease in caspase-3 activity, although the mechanism of this process remains unclear. We hypothesize that resistance production in neurons is mediated by a decrease in caspase-3 activity as a result of autophagy activation.

The aim of the present work was to study the dynamics of neurotransmitter amino acids after acute Noopept (a dipeptide analogue of piracetam used in clinical practice as a nootropic agent) administration in intact and long-term ethanol (ETOH) exposed rats. Albino male rats were given 10% (vol/vol) ETOH solution as the only source of fluid 24 h / 7 days per week (n = 5). Also we used intact rats of the same age which had no access to ethanol (n = 5). The excitatory and inhibitory amino acids in the extracellular space of the dorsal hippocampus region in freely moving intact and ETOH-exposed rats during prolonged alcohol deprivation were measured using the intracerebral microdialysis method followed by HPLC/ED. There were no significant differences in the level of neurotransmitter amino acids between ETOH-exposed and intact animals. For the first time, in vivo experiments the effect of Noopept (1.5 mg/kg, i.p.) on the level of excitatory amino acids (an increase in ASP by 2.38 times and GLU by 2.28 times) along with an increase in the level of the inhibitory amino acid GLI by 3.13 times only in intact rats was shown. Thus, in ETOH-exposed rats under the adaptive rearrangements in prolonged ethanol withdrawal, the neurochemical mechanisms of the hippocampus seem to be characterized by insensitivity to an acute Noopept administration. Animal neurochemical studies of changes in the mediator amino acids due to the long-term effect of alcohol on the CNS may be of practical importance for the development of optimal strategies and pharmacotherapy.

The effect of the antiepileptic compound GIZH-298 and the reference drug sodium valproate (VN) on the content of excitatory and inhibitory amino acids in the frontal cortex, hypothalamus, striatum, and hippocampus of the brain of mice after an electric shock-induced generalized tonic-clonic seizure (MES) was studied. It has been shown that the application of MES reduces the levels of aspartate, glycine, GABA and the ratio of “GABA/glutamate” in the hypothalamus. In the latter, a decrease in the concentration of glutamate, glycine and taurine was noted. VN (200 mg/kg/g) counteracts the effects of MES by interfering with the resulting decrease in GABA and the GABA/glutamate ratio in the hypothalamus. In the hypothalamus, striatum, and hippocampus, VN causes a decrease in the aspartate content both in intact control groups and in the group of mice that received MES. GIZH-298 (60 mg/kg/int. gastric) prevented the MES-induced decrease in the levels of GABA, glycine and taurine and the GABA/glutamate ratio in the hypothalamus.

Post-stroke depressive disorders (PSD) and post-stroke cognitive impairments (PCI) are frequent consequences of ischemic stroke (IS). The study was focused on exploring possible associations between relative volumes of cortical and limbic brain structures during the acute period of IS, and changes in biochemical indices of hypothalamic-pituitary-adrenal, sympathoadrenal medullary and inflammatory systems, with the development of PSD or PCI after mild or moderate IS. Patients developing PSD later on had significantly smaller relative volumes of the hippocampus, entorhinal cortex, and temporal pole versus patients without depressive symptoms. PCI development was associated with significantly smaller volumes of temporal pole and supramarginal gyrus versus patients without cognitive changes. Multiple logistic regression analysis showed higher likelihood of developing PSD in patients with smaller temporal pole volume (β₀ =10.9; β = –4.27; p = 0.04) and in-creased salivary α-amylase activity (β₀ = –3.55; β = 2.68e–05; p = 0.02). PCI likelihood was higher in patients with smaller supramarginal gyrus volume (β₀ = 3.41; β = –0.99; p = 0.047), smaller temporal pole volume (β₀ = 3.41; β = –3.12; p = 0.06), and increased hair cortisol concentration at admission (index of accumulated stress load within a month before IS; β₀ = 3.41; β = –0.05; p = 0.08). The data support the hypothesis suggesting predisposition to PSD and PCI and multi hit scenarios of their pathogenesis with IS providing a final hit.