Raman scattering spectroscopy of MBE grown thin film topological insulator Bi2-xSbxTe3-ySey.

BSTS epitaxial thin film topological insulators were grown using the MBE technique on two different types of substrates i.e., Si (111) and SiC/graphene with Bi0.7Sb1.6Te1.8Se0.9 and Bi0.9Sb1.5Te1.8Se1.1, respectively. The crystallographic properties of BSTS films were investigated via X-ray diffraction, which showed the strongest reflections from the (0 0 l) facets corresponding to the rhombohedral phase. Superior epitaxial growth, homogeneous thickness, smooth surfaces, and larger unit cell parameters were observed for the films grown on the Si substrate. Polarization dependent Raman spectroscopy showed a weak appearance of the Ag mode in cross--polarized geometry. In contrast, a strong Eg mode was observed in both parallel and cross-polarized geometries which correspond to the rhombohedral crystal symmetry of BSTS films. A redshift of Ag and Eg modes was observed in the Raman spectra of BSTS films grown on the Si substrate, compared to those on SiC/graphene, which was directly associated with the unit cell parameter and composition of the films. Raman spectra showed four fundamental modes with asymmetric line shape, and deconvolution of the peaks resulted in additional modes in both the BSTS thin films. The sum of relative ratios of linewidths of fundamental modes (Ag and Eg) of BSTS films grown on Si substrate was lower, indicating a more ordered structure with lower contribution of defects as compared to BSTS film grown on SiC/graphene substrate.

Cytotoxicity of Laser-Synthesized Nanoparticles of Elemental Bismuth.

High X-ray absorption combined with photothermal properties make bismuth nanoparticles (Bi NP) a promising agent for multimodal cancer theranostics. However, the synthesis of Bi NP by the "classical" chemical methods has numerous limitations, including potential toxicity of the produced nanomaterials. Here we studied in vitro toxicity of laser-synthesized Bi NP coated with Pluronic F-127 on mouse fibroblast cell line L929. The survival of L929 cells decreased linearly with increasing the concentration of Bi NP in a concentration range of 3-500 µg/ml; the LC50 value was 57 µg/ml. The unique combination of functional properties and moderate toxicity of the laser-synthesized Bi NP makes them a new promising platform for sensitization of multimodal cancer theranostics.

[Interleukin-11 in Pathologies of the Nervous System].

The study of the role of cytokines in various pathological conditions of the body is a topical area in modern biomedicine. Understanding the physiological roles played by cytokines will aid in finding applications for them as pharmacological agents in clinical practice. Interleukin 11 (IL-11) was discovered in 1990 in fibrocyte-like bone marrow stromal cells, but there has been increased interest in this cytokine in recent years. IL-11 has been shown to correct inflammatory pathways in the epithelial tissues of the respiratory system, where the main events occur during SARS-CoV-2 infection. Further research in this direction will probably support the use of this cytokine in clinical practice. The cytokine plays a significant role in the central nervous system; local expression by nerve cells has been shown. Studies show the involvement of IL-11 in the mechanisms of development of a number of pathologies of the nervous system, and therefore it seems relevant to generalize and analyze the experimental data obtained in this direction. This review summarizes information that shows the involvement of IL-11 in the mechanisms of development of brain pathologies. In the near future this cytokine will likely find clinical application for the correction of mechanisms that are involved in the formation of pathological conditions of the nervous system.

Prospects for the use of graphene-based biological sensors in the early diagnosis of Alzheimer's disease (review of literature).

Among the most significant challenges presented to modern medicine is the problem of cognitive disorders. The relevance of her research is determined by the wide spread of disorders of the higher cortical functions, their significant negative impact on the quality of life of patients, as well as high economic costs on the part of the state and the patient's relatives aimed at organizing medical, diagnostic and rehabilitation processes. The main cause of cognitive impairment in the elderly is Alzheimer's disease. Currently, the criteria for the diagnosis of this nosological form have been developed and are widely used in practice. However, it should be noted that their use is most effective if the patient has a detailed clinical picture, at the stage of dementia. In addition, they provide for the study of biomarkers in a number of cases in the cerebrospinal fluid or using positron emission tomography, which presents certain technical difficulties. Especially significant problems arise in the pre-dement stages. This situation dictates the need to search for new promising diagnostic methods that will have high sensitivity and specificity, as well as the possibility of application in the early stages of Alzheimer's disease, including in outpatient settings. The article provides information about modern methods of computer neuroimaging, discusses the research directions of individual biomarkers, and also shows the prospects for using diagnostic test panels developed on the basis of graphene biosensors, taking into account the latest achievements of nanotechnology and their integration into medical science.

[Expression of Ghrelin Receptor GHS-R1a in The Brain (Mini Review)].

The review presents data on the expression of ghrelin receptor GHS-R1a in the brain in model animals (Danio rerio, rodents, primates), and in the human brain. Studies show widespread localization of GHS-R1a in the brain, which indicates the involvement of the receptor in many physiological processes. Using various models, information has been obtained regarding the participation of the receptor in the regulation of the pro- and anti-inflammatory response, apoptosis and proliferation. It is known that the ghrelin receptor plays an important role in eating behavior and is also involved in the pathogenetic mechanisms of obesity, drug addiction, and alcoholism. With this in mind, research is underway with the use of various therapeutic agents (receptor agonists and antagonists) that can be used for the pharmacological correction of these pathological conditions. This review also presents hypothetical mechanisms of intracellular signaling, in which GHS-R1a may participate; however, a complete understanding of these mechanisms has not yet been reached. The ghrelin intracellular pathways seem to be specific to brain region and, probably, also depend on the metabolic or stress status of the organism.

Prolonged alcohol consumption influences microRNA expression in the nucleus accumbens of the rat brain.

The microRNA (miR) species analyzed in this study are involved in molecular mechanisms of TLR4 and TLR7 signaling, mediating the development of neuroinflammation and neurodegeneration. We have investigated the expression levels of miR-let7b, miR-96, miR-182, miR-155, and the mRNA content of HMGB1, TLR3, TLR4 in the nucleus accumbens (NAc) of the brain of rats exposed to long-term alcoholization. The long-term alcoholization caused a decrease in miR-let7b, miR-96, miR-182, and TLR7 mRNA levels; this was accompanied by an increase in miR-155, TLR4, and Hmgb1 mRNA levels in the NAc of rat brain. TLR7 is functionally linked to miR-let7b. The data of a simultaneous decrease in miR-let7b and TLR7 mRNA are of interest for further studies; they may indicate on the lack of functionally significant links between Hmgb1 and the miR-let7b-TLR7 system in NAc. The existing evidence of a functional relationship between TLR4 with miR-155 and miR-182 and our observations on their expression changes during chronic alcoholization are very interesting and require further investigation. The suggestion about the development of neuroinflammatory process in NAc under prolonged alcohol exposure are relevant for studying the level of TLR gene expression in NAc, as well as the expression of miR species, which may have a functional relationship with the TLR system.

Interleukin-11 in Pathologies of the Nervous System.

The study of the role of cytokines in various pathological conditions of the body is a topical area in modern biomedicine. Understanding the physiological roles played by cytokines will aid in finding applications for them as pharmacological agents in clinical practice. Interleukin 11 (IL-11) was discovered in 1990 in fibrocyte-like bone marrow stromal cells, but there has been increased interest in this cytokine in recent years. IL-11 has been shown to correct inflammatory pathways in the epithelial tissues of the respiratory system, where the main events occur during SARS-CoV-2 infection. Further research in this direction will probably support the use of this cytokine in clinical practice. The cytokine plays a significant role in the central nervous system; local expression by nerve cells has been shown. Studies show the involvement of IL-11 in the mechanisms of development of a number of pathologies of the nervous system, and therefore it seems relevant to generalize and analyze the experimental data obtained in this direction. This review summarizes information that shows the involvement of IL-11 in the mechanisms of development of brain pathologies. In the near future this cytokine will likely find clinical application for the correction of mechanisms that are involved in the formation of pathological conditions of the nervous system.

The effect of rifampicin on expression of the toll-like receptor system genes in the forebrain cortex of rats prenatally exposed to alcohol.

Ethanol causes long-term changes in the toll-like receptor (TLR) system, promoting activation of neuroinflammation pathways. Alcohol use during pregnancy causes neuroinflammatory processes in the fetus; this can lead to the development of symptoms of fetal alcohol spectrum disorder (FASD). Our study has shown that prenatal alcohol exposure (PAE) induced long-term changes in the TLR system genes (Tlr3, Tlr4, Ticam, Hmgb1, cytokine genes) in the forebrain cortex of rat pups. Administration of rifampicin (Rif), which can reduce the level of pro-inflammatory mediators in various pathological conditions of the nervous system, normalized the altered expression level of the studied TLR system genes. This suggests that Rif can prevent the development of persistent neuroinflammatory events in the forebrain cortex of rat pups caused by dysregulation in the TLR system.

[Effect of ethanol on platelet biology]. / Vliianie étanola na biologiiu trombotsitov.

In recent years, interest in the study of platelets, significantly increased due to recent discoveries providing convincing evidence that their functions by are not limited to their participation in the blood coagulation mechanism. Many works are devoted to the study of the functional state of platelets under conditions of acute and chronic alcohol exposure. The results of such studies can be useful for the development of new markers of the degree of alcohol intoxication of the body for the subsequent choice of the method drug correction of disorders caused by acute or chronic alcohol effects. The review summarizes results in vivo and in vitro of studies performed during more than 60 years on the effect of ethanol on the biogenesis, number, morphology and biochemistry of platelets.

[Ginsenosides affect the system of Toll-like receptors in the brain of rats under conditions of long-term alcohol withdrawal]. / Ginzenozidy vliiaiut na sistemu Toll-podobnykh retseptorov v strukturakh golovnogo mozga krys v usloviiakh otmeny dlitel'noi alkogolizatsii.

Long-term alcohol consumption causes the development of neuroinflammation in various brain structures. One of the mechanisms involved in this process is the increased activity of TLR-signaling intracellular pathways. Studies confirm the ability of ginseng extract or its individual ginsenosides to reduce the increased activity of TLR-signaling pathways. The aim of our study was to study the effect of the amount of ginsenosides obtained from the extract of the Panax japonicus cell line on the state of the TLR-signaling system in the nucleus accumbens and hippocampus of the rat brain in a model of long-term alcohol consumption during alcohol withdrawal. The results of the study showed that ginsenosides were able to make changes in the TLR signaling system, which has been altered by long-term alcohol consumption. A significant effect of ginsenosides on the level of TLR3 and TLR4 mRNA in the nucleus accumbens was found, while in the hippocampus, ginsenosides significantly affected the level of TLR7 mRNA. The effect of ginsenosides on the level of mRNA of transcription factors and cytokines involved in TLR-signaling was evaluated. Thus, results of our study confirm that ginsenosides are able to influence the state of TLR-signaling pathways, but this effect is multidirectional in relation to different brain structures. In the future, it seems interesting to evaluate the role of individual ginsenosides in relation to genes of TLR-signaling, as well as the effect of ginsenosides on other brain structures.

[The effect of rifampicin on the system of Toll-like receptors in the nucleus accumbens of the brain of long-term alcoholized rats during alcohol withdrawal]. / Vliianie rifampitsina na sistemu Toll-podobnykh retseptorov v prilezhashchem iadre mozga dlitel'no alkogolizirovannykh krys v period otmeny alkogolia.

Nucleus accumbens (NAc) is the ventral part of the striatum of the brain; it is an important part of the mesolimbic pathway involved in the reward system that mediates the formation of various forms of addiction, in particular alcohol addiction. Neuroimaging data and in vitro studies indicate the development of a pronounced neurodegenerative process in the NAc, with long-term alcohol use, but the key mechanisms mediating this process remain unknown. In recent years, the attention of researchers has been focused on studying the system of Toll-like receptors (TLRs), the increased activity of which is clearly shown in the cerebral cortex and hippocampus during prolonged alcohol exposure, but there is a need to study the role of this system in other brain structures. In this study, we have shown that prolonged alcohol exposure (2 months) with moderate doses of ethanol (2 g/kg) promotes a pronounced increase in the expression of the Tlr4 gene and its endogenous ligand Hmgb1 in NAc during the period of alcohol withdrawal in rats. Injections of rifampicin (100 mg/kg) reduced the elevated expression level of Hmgb1, Tlr4, as well as pro-inflammatory cytokine genes (IL1ß, IL6), while the administration of the drug increased the reduced level of mRNA of anti-inflammatory cytokines (IL10, IL11).

[Behavioral correlations of gradual forced administration of psychoactive drugs].

The study was aimed at evaluating the behavioral correlations of the forced administration of psychoactive drugs. Wistar rats received the following drugs in elevated doses (over 4 days, i. p.): (i) physiological saline (control; 0.1-0.2-0.4-0.8 ml/rat), (ii) psychostimulant amphetamine (0.5-1.0--2.0-4.0 mg/kg); (iii) opioid analgetic fentanyl (0.00625-0.0125--0.025-0.05 mg/kg), (iv) ethanol 40% solution (0.5-1.0--2.0-4.0 g/kg), (v) barbiturate sodium ethaminal (2.5-5--10-20 mg/kg); and(vi) synthetic glucocorticoid dexamethasone (0.5-1.0--2.0-4.0 mg/kg). The forced regime of drug administration led to gradual load of the organism and prevented drug tolerance. The dynamics of self-stimulation reaction of the lateral hypothalamus was registered every day over drug administration period and revealed the following regularities: (I) dose-dependent effect of psychostimulant amphetamine and opioid analgetic fentanyl; (II) dexamethasone modulated self-stimulation, increasing (2 day, 1 mg/kg) or decreasing it (3 day, 2 mg/kg); (III) ethanol (1-2 g/kg) activated self-stimulation slightly; (IV) sodium ethaminal slightly inhibited self-stimulation and increased the thresholds of self-stimulation. In 24 h and 72 h after the last administration of drugs, the rat behavior was assessed in open field, elevated plus maze, resident-intruder paradigm, and Porsolt's test. In the open field, significant signs of post-intoxication exposure of psychoactive drugs were revealed, which were registered for 24-72 h after drug withdrawal. The withdrawal of drugs was accompanied with reduction (in 24 h) and subsequent recovery (in 72 h) of the vertical motor activity, exploration behavior, and emotionality. The anxiety indexes were increased up to the 3rd day after withdrawal. The antidepressant effect was also increased. The system of aggression-defense was restored only in rats treated with ethanol. The indexes of individual behavior and communicability in the post-intoxication period were decreased as well. It is suggested that the forced regime of drug administration in increasing doses with subsequent withdrawal of drug injections is a suitable method to evaluate the behavioral elements of drug dependence.

[Significance of CRF and dopamine receptors in amygdala for reinforcing effects of opiates and opioids on self-stimulation of lateral hypothalamus in rats].

Bipolar electrodes were implanted in the lateral hypothalamus in a group of 44 Wistar male rats in order to study self-stimulation reaction in the Skinner box. Simultaneously, microcanules were implanted into the central nucleus of the amygdala to inject the drugs (1 microl per injection). The blockade of corticoliberin (CRF) receptors (astressin, 1 microg) or Na+influx currents (xycaine or lidocain 1 microg) by the intrastructural administration of drugs into the amygdala decreased self-stimulation reaction of the lateral hypothalamus in rats by 29-55%. The inhibition of D1 and D2 dopamine receptors in the amygdala with SCH23390 (1 microg) or sulpiride (1 microg) respectively, also reduced self-stimulation but to a lower degree. On the background of blockade of CRF (astressin) and dopamine (sulpiride) receptors as well as sodium influx ionic currents (lidocain) in the amygdala neurons, psychomotor stimulant amphetamine (1 mg/kg) and barbiturate sodium ethaminal (5 mg/kg) retained their psychoactivating effect on self-stimulation (+30-37%), while fentanyl (0.1 mg/kg) and leu-enkephaline (0.1 mg/kg) did not produce this effect. Fentanyl moderately activated self-stimulation only after the blockade of D1 dopamine receptors with SCH23390. After the blockade of CRF receptors, leu-enkephaline strengthened its depressant effect on self-stimulation reaction (-89%). Therefore, if the modulating action of amygdala on the hypothalamus is eliminated, the enhancing effects of opiates (fentanyl) and opioids (leu-encephaline) are blocked, but the effects of psychomotor stimulant amphetamine and barbiturate sodium ethaminal are retained.

[Prenatal exposure to alcohol alters TLR4 signaling in the prefrontal cortex in rats]. / Prenatal'noe vozdeistvie alkogolia izmeniaet TLR4-oposredovannuiu signalizatsiiu v prefrontal'noi kore golovnogo mozga u krys.

Prenatal alcohol exposure (PAE) can lead to developmental disorders of the central nervous system (CNS) and mental retardation. Toll-like receptor (TLR) 4 plays an important role in the development of defects in the nervous system caused by PAE. However, how PAE affects the TLR4 response in the brain remains unclear. Using the model of semi-forced alcoholization of pregnant rats, we investigated TLR4-mediated signaling on the 30th day of postnatal development in their offspring. Rats exposed to PAE showed a higher expression of proinflammatory cytokines in the prefrontal cortex, but TLR4-mediated signaling in response to lipopolysaccharide (LPS) was weakened. These data suggest that PAE can lead to neuroinflammation and suppression of the TLR4-mediated response to LPS in the prefrontal cortex of young rats. Since innate immunity plays an important role in brain development, PAE-induced suppression of the TLR4-mediated response may be one of the mechanisms for the development of CNS pathology.

[HMGB1gene expression changes in the striatum and amigdal of the rat's brain under alcoholization and ethanol withdrawal]. / Ékspressiia gena HMGB1 izmeniaetsia v striatume i amigdale mozga krys pri dlitel'noi alkogolizatsii i otmene étanola.

Intracellular signaling mediated by the HMGB1 protein, an agonist of TLRs, is considered as a possible target for the correction of pathologies of the neuroimmune system, however, the expression level of the Hmgb1 gene has not been previously studied in various brain structures of rats exposed to prolonged alcoholization followed by ethanol withdrawal. The study showed that long-term use of ethanol caused to an increase in the level of Hmgb1 mRNA in the striatum of rat brain. Alcohol withdrawal changed the level Hmgb1 mRNA in the striatum and amygdala on the 1st and 14th day. The data obtained may indicate that in different structures of the brain there are multidirectional changes in the molecular mechanisms of the neuroimmune response with prolonged use of ethanol and its withdrawal.

[The TLR3 induction increases content of interferons in rat's brain by TRAIL signaling during long-term alcoholization]. / Induktsiia TLR3 pri dlitel'noi alkogolizatsii uvelichivaet soderzhanie interferonov v golovnom mozge u krys posredstvom TRAIL-signalizatsii.

The pathogenetic mechanisms associated with alcohol use include dysregulation of the innate immune system mechanisms in the brain. TLR3 expression is increased in the postmortem material of the prefrontal cortex of humans. An increase in the TLR3 signaling activity leads to the induction of interferons (IFN). IFN are associated with depressive symptoms and, therefore, may play a role in the pathogenesis of alcoholism; however, the exact mechanisms of intracellular signaling mediated by the influence of ethanol are not fully elucidated and their study was the purpose of this work. The experimental results showed that ethanol and the TLR3 agonist Poly (I:C) increased the content of TLR3, IFNß, and IFNγ mRNA in the prefrontal cortex. In addition, expression of the TRAIL encoding gene also increased, and this increase positively correlaed with the mRNA content of TLR3, IFNß and IFNγ both under alcoholization conditions and after injections of the TLR3 agonist. The data obtained may indicate that alcoholization is able to activate TLR3-TRAIL-IFN-signaling in the prefrontal cortex of the brain.

[Increase in the level of orexin receptor 1 (OX1R) mRNA in the brain structures of rats prone to impulsivity in behavior]. / Povyshenie urovnia mRNK retseptora oreksina pervogo tipa (OX1R) v strukturakh golovnogo mozga u krys, sklonnykh k impul'sivnosti v povedenii.

Orexin and its receptors are involved in the mechanisms of pathological craving for alcohol and psychoactive drugs. The orexin system is also involved in the mechanisms of non-chemical forms of addiction: binge eating and gambling. The aim of this work was to study the level of orexin receptor mRNA in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior in a model for studying the elements of gambling addiction (a variant of the Iowa Gambling Task test). Brain structures were isolated on the 22nd day of the experiment. The expression of the OX1R gene was higher in the hypothalamus by 122% and in the hippocampus by 149% in rats that preferred to receive a high reward, but with a low probability as compared with a group of animals that preferred a low level of reinforcement, but with a 100% probability. In the prefrontal cortex, on the contrary, no significant changes were observed in the level of OX1R mRNA. The level of OX2R mRNA insignificantly changed in the hypothalamus, hippocampus, and prefrontal cortex of rats prone to impulsivity in behavior. The data indicate involvement of OX1R in the hypothalamus and hippocampus in mechanisms mediating impulsive behavior and the choice of the significance of positive reinforcement in terms of its varying strength and probability.

[Surgical correction of overactive bladder resistant to standard therapy].

Surgical treatment was given to 45 patients with overactive bladder: transurethral detrusorotomy was made in 21 patients (group 1), bladder hydrodilation (BH) was made in 24 patients (group 2). Detrusorotomy was performed by transurethral median cut of the bladder posterior wall by needle electrode leading to destroyment of intramural sympathic and parasympathic nervous fibres. Hydrodilation of the bladder was made under intravesical pressure equal to systolic arterial pressure with 2 min exposure. On day thirty after the operation regress of the lower urinary tract symptoms was registered in 20 (95.2%) patients of group 1 and 11 (45.8%) patients of group 2. Urge to voiding (UV) disappeared in 90.5% patients of group 1 and in 45.8% of group 2 (p < 0.05), the number of patients with miction pain reduced 6-fold and 1.9-fold, with UV--8.5 and 1.2-fold, respectively (p < 0.05). The number of diurnal mictions in group 1 decreased 3.2-fold vs 1.9-fold in group 2. The bladder size in urgency in group 1 patients increased 2.5-fold, the pressure fell also 2.5-fold. In group 2 these parameters changed only 1.2 times (p < 0.05). Cystometry recorded recurrent detrusor overactivity in 13 (54.2%) patients after hydrodilation and only in 3 (14.3%)--after cut of the bladder wall (p < 0.05). Thus, transurethral detrusorotomy in overactive bladder resistant to conventional treatment is much more effective than hydrodilation. The operation is low invasive and is well tolerated. Simple performance and good short-time results are advantages of this technique.

Low-temperature quantum magnetotransport of graphene on SiC (0 0 0 1) in pulsed magnetic fields up to 30 T.

Resistivity, ρ(T), and magnetoresistance (MR) are investigated in graphene grown on SiC (0 0 0 1), at temperatures between T ~ 4-85 K in pulsed magnetic fields of B up to 30 T. According to the Raman spectroscopy and Kelvin-probe microscopy data, the material is a single-layer graphene containing ~20% double-layer islands with a submicron scale and relatively high amount of intrinsic defects. The dependence of ρ(T) exhibits a minimum at temperature T m ~ 30 K. The low-field Hall data have yielded a high electron concentration, n R ≈ 1.4 × 1013 cm-2 connected to intrinsic defects, and a mobility value of µ H ~ 300 cm2 (Vs)-1 weakly depending on T. Analysis of the Shubnikov-de Haas oscillations of MR, observed between B ~ 10-30 T, permitted to establish existence of the Berry phase ß ≈ 0.55 and the cyclotron mass, m c ≈ 0.07 (in units of the free electron mass) close to expected values for the single-layer graphene, respectively. MR at 4.2 K is negative up to B ~ 9 T, exhibiting a minimum near 3 T. Analysis of MR within the whole range of B = 0-10 T below the onset of the SdH effect has revealed three contributions, connected to (i) the classical MR effect, (ii) the weak localization, and (iii) the electron-electron interaction. Analysis of the ρ(T) dependence has confirmed the presence of the contributions (ii) and (iii), revealing a high importance of the electron-electron scattering. As a result, characteristic relaxation times were obtained; an important role of the spin-orbit interaction in the material has been demonstrated, too.

[Involvement of TOLL-like receptors in the neuroimmunology of alcoholism]. / Rol' TOLL-podobnykh retseptorov v neiroimmunologii alkogolizma.

Alcohol use is a global socially significant problem that remains one of the leading risk factors for disability and premature death. One of the main pathological characteristics of alcoholism is the loss of cognitive control over the amount of consumed alcohol. Growing body of evidence suggests that alterations of neuroimmune communication occurring in the brain during prolonged alcoholization are one of the main mechanisms responsible for the development of this pathology. Ethanol consumption leads to activation of neuroimmune signaling in the central nervous system through many types of Toll-like receptors (TLRs), as well as the release of their endogenous agonists (HMGB1 protein, S100 protein, heat shock proteins, extracellular matrix breakdown proteins). Activation of TLRs triggers intracellular molecular cascades leading to increased expression of the innate immune system genes, particularly proinflammatory cytokines, subsequently causing the development of a persistent neuroinflammatory process in the central nervous system, which results in massive death of neurons and glial cells in the brain structures, which are primarily associated with the development of a pathological craving for alcohol. In addition, some subtypes of TLRs are capable of forming heterodimers with neuropeptide receptors (corticoliberin, orexin, ghrelin receptors), and may also have other functional relationships.