Depression poses a major global health challenge, highlighting the urgent need for valid animal models to elucidate its pathogenesis and develop novel treatments. This review offers a comprehensive characterization and validation of an original rodent model of depression induced by chronic exposure to variable-frequency ultrasound (20-45 kHz), termed the ultrasound model (US-model). We hypothesize that this model uniquely recapitulates a state of "information uncertainty", providing a highly relevant framework for studying depression amid modern urban environments. Based on extensive experimental data collected over 10 years (2013-2024), the model has been systematically evaluated using three key criteria for validity. First, the US-model demonstrates face validity, recapitulating core behavioral abnormalities such as anhedonia, behavioral despair, social withdrawal, anxiety, and cognitive deficits. Second, its construct validity is supported by the faithful reproduction of key pathophysiological mechanisms, including monoamine system dysfunction, impaired neuroplasticity, neuroinflammation, oxidative stress, and hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. Finally, the model exhibits strong predictive validity, showing sensitivity to various established classes of antidepressants (e.g., fluoxetine, clomipramine), novel compounds (e.g., vindeburnol, neuropeptides), electroconvulsive therapy, and agents with antioxidant or anti-inflammatory properties. Compared to classic models, the US-model may offer several potential advantages such as a relatively high degree of standardization and an arguably more ethical profile, as it is less invasive. In conclusion, the US-model of depression represents a reliable and reproducible tool to investigate the pathogenesis of affective disorders and screen new therapeutic agents.

Alzheimer's disease (AD) remains an incurable neurodegenerative disorder. The concept of theranostics-combining diagnostic and therapeutic functions within a single nanoplatform-has been explored for over a decade. Despite a growing number of publications, no theranostic system has yet reached clinical application for AD. This critical review analyzes the fundamental conceptual contradictions that hinder the clinical translation of theranostic nanoplatforms for AD and identifies alternative strategies where nanotechnology may still be beneficial. The review presents key aspects essential for understanding theranostics challenges: AD molecular targets, analysis of existing nanoplatforms, identification of three inherent conceptual conflicts, and viable alternative approaches. Our analysis reveals three core conceptual conflicts: the pharmacokinetic conflict, where diagnostics demand rapid accumulation and clearance while therapy requires prolonged retention-exacerbated by minimal brain delivery (1-2% ID/g) and peripheral toxicity risks; the dose conflict, characterized by orders-of-magnitude disparities between diagnostic and therapeutic dosing, rarely quantified for identical particles; and the temporal conflict, pitting one-time diagnostics against chronic therapy needs, as long-persisting particles generate irremovable brain background signals. We further identify a pervasive methodological trap: predominant focus on mature β-amyloid (Aβ) fibrils overlooks soluble oligomers as the primary toxic species. We conclude by proposing viable alternatives: preclinical intervention for time-limited "hit-and-clear" applications; coordinated theranostic monitoring with separate diagnostics/therapy; theranostic pairs using ligand-matched, function-optimized particles; and external stimuli for temporal function separation. A practical roadmap guides the transition from conceptual demonstrations to clinical translation. Addressing these contradictions can transform theranostics from elegant chemical constructs into clinically meaningful AD tools.

Objective: Alzheimer's disease (AD) and other forms of dementia are a heterogeneous group of neurodegenerative diseases characterized by progressive cognitive decline. Differential diagnosis between AD and other dementias is crucial for choosing the optimal treatment strategy. Currently, cerebrospinal fluid (CSF) analysis remains the most accurate diagnostic method, but its invasiveness limits its use. In this regard, the search for reliable biomarkers in the blood is an urgent task. Methods: The study included 31 dementia patients (23 women and 8 men) diagnosed via interdisciplinary consultations and neuropsychological testing (MMSE <= 24). CSF and blood plasma samples were collected and analyzed using Luminex technology. Biomarker concentrations were measured, and statistical analyses (ANOVA, Kruskal-Wallis, and Pearson correlation) were performed to compare groups and assess correlations. Results: Levels of A beta 40 and A beta 42 in CSF were significantly lower in patients with AD compared with non-AD dementia (p = 0.02 and p < 0.001, respectively). The A beta 42/40 ratio in CSF was higher in patients with non-AD dementia (p = 0.048). The concentration of A beta 42 in blood plasma was increased in patients with AD (p = 0.001). Positive correlations were found between A beta 42 in CSF and TDP-43 in plasma in non-AD dementia (r = 0.97, p < 0.001), as well as between neurogranin and TDP-43 in plasma in AD (r = 0.845, p < 0.001). Conclusions: The study demonstrates the potential of blood biomarkers, in particular A beta 42, for the differential diagnosis of AD and other forms of dementia. The discovered correlations between CSF and plasma biomarkers deepen the understanding of neurodegenerative processes and contribute to the development of noninvasive diagnostic methods.

Cognitive impairment is a common symptom of many psychiatric disorders and can significantly reduce the patients' quality of life. Vindeburnol, a synthetic derivative of eburnamine-vincamine alkaloids, has shown potential in models of depression and neurodegeneration; however, its comprehensive properties and molecular mechanisms of action have remained unexplored. We conducted a comprehensive preclinical assessment of vindeburnol, including a subchronic toxicity study (20 and 80 mg/kg/day, orally, 14 days), pharmacokinetic analysis (40 mg/kg), behavioral tests for memory and learning, and transcriptomic profiling of the locus coeruleus (LC) in mice. Vindeburnol demonstrated a good safety profile at 20 mg/kg, while the 80 mg/kg dose caused 20% mortality and hepatotoxicity. The compound exhibited high oral bioavailability (75%) and a long half-life (7.58 h). Behavioral analysis revealed a specific improvement in episodic memory in the novel object recognition test without affecting motor activity. Transcriptomic analysis of the LC identified 10 differentially expressed genes, including the upregulation of Npas3 and Cfap69, key regulators of neurogenesis and synaptic plasticity, and the downregulation of genes associated with neuroinflammation (Ctss, Hspa1b). Our study is the first to comprehensively characterize vindeburnol as a promising compound with proven procognitive effects. The data reveal its unique mechanism of action, which promotes neuroplasticity and counteracts pathological processes by modulating key transcriptional programs in the locus coeruleus, supporting its further investigation as a potential neurotropic agent.

The prevalence of mental disorders and how they are diagnosed represent some of the major problems in psychiatry. Modern genetic tools offer the potential to reduce the complications concerning diagnosis. However, the vast genetic diversity in the world population requires a closer investigation of any selected populations. In the current research, four polymorphisms, namely rs6265 in BDNF, rs10835210 in BDNF, rs6313 in HTR2A, and rs1800955 in DRD4, were analyzed in a case–control study of 2393 individuals (1639 patients with mental disorders (F20-F29, F30-F48) and 754 controls) from the European part of Russia using the TaqMan SNP genotyping method. Significant associations between rs6265 BDNF and rs1800955 DRD4 and mental impairments were detected when comparing the general group of patients with mental disorders (without separation into diagnoses) to the control group. Associations of rs6265 in BDNF, rs1800955 in DRD4, and rs6313 in HTR2A with schizophrenia in patients from the schizophrenia group separately compared to the control group were also found. The obtained results can extend the concept of a genetic basis for mental disorders in the Russian population and provide a basis for the future improvement in psychiatric diagnostics.

Inflammatory bowel diseases are extremely common throughout the world. However, in most cases, it is asymptomatic at the initial stage. Therefore, it is important to develop non-invasive diagnostic methods that allow identification of the IBD risks in a timely manner. It is well known that gastrointestinal microbiota secrete volatile compounds (VOCs) and their composition may change in IBD. We propose a non-invasive method to identify the dynamics of IBD development in the acute and remission stage at the level of VOCs in model of dextran sulfate sodium (DSS) with chemically induced colitis measured by headspace GC/MS (HS GC/MS). Methods: VOCs profile was identified using a headspace GC/MS (HS GC/MS). GC/MS data were processed using MetaboAnalyst 5.0 and GraphPad Prism 8.0.1 software. The disease activity index (DAI) and histological method were used to assess intestinal inflammation. The peak of intestinal inflammation activity was reached on day 7, according to the disease activity index. Histological examination data showed changes in the intestine due to different stages of inflammation. As the acute inflammation stage was reached, the metabolomic profile also underwent changes, especially at the short-fatty acids level. A higher relative amounts of acetic acid (p value < 0.025) and lower relative amounts of propanoic acid (p value < 0.0005), butanoic acid (p value < 0.005) and phenol 4-methyl- (p value = 0.053) were observed in DSS7 group on day 7 compared to the control group. In remission stage, disease activity indexes decreased, and the histological picture also improved. But metabolome changes continued despite the withdrawal of the DSS examination. A lower relative amounts of propanoic acid (p value < 0.025), butanoic acid (p value < 0.0005), pentanoic acid (p value < 0.0005), and a significant de-crease of hexanoic acid (p value < 0.0005) relative amounts were observed in the DSS14 group compared to the control group on day 14. A model of DSS-induced colitis in rats was successfully implemented for metabolomic assessment of different stages of inflammation. We demonstrated that the ratios of volatile compounds change in response to DSS before the appearance of standard signs of inflammation, determined by DAI and histological examination. Changes in the volatile metabolome persisted even after visual intestine repair and it confirms the high sensitivity of the microbiota to the damaging effects of DSS. The use of HS GC/MS may be an important addition to existing methods for assessing inflammation at early stages.

Vindeburnol (VIND, RU24722, BC19), a synthetic molecule derived from the eburnamine-vincamine alkaloid group, has many neuropsychopharmacological effects, but its antidepressant-like effects are poorly understood and have only been described in a few patents. To reliably estimate this effect, vindeburnol was studied in a model of long-term variable-frequency ultrasound (US) exposure at 20-45 kHz in male Wistar rats and BALB/c mice. Vindeburnol was administered chronically for 21 days against a background of simultaneous ultrasound exposure at a dose of 20 mg/kg intraperitoneally (IP). Using four behavioral tests, the sucrose preference test (SPT), the social interaction test (SIT), the open field test (OFT), and the forced swimming test (FST), we found that the treatment with the compound diminished depression-like symptoms in mice and rats. The compound restored the ultrasound-related reduced sucrose consumption to control levels and increased social interaction time in mice and rats compared with those in ultrasound-exposed animals. Vindeburnol showed contraversive results of horizontal and vertical activity in both species and generally did not increase locomotor activity. At the same time, the compound showed a specific effect in the FST, significantly reducing the immobility time. Moreover, we found an increase in norepinephrine, dopamine, and its metabolite levels in the brainstem, as well as an increase in dopamine, 3-methoxytyramine, and 3,4-dihydroxyphenylacetic acid levels in the striatum. We also observed a statistically significant increase in tyrosine hydroxylase (TH) levels in the region containing the locus coeruleus (LC). We suggest that using its distinct chemical structure and pharmacological activity as a starting point could boost antidepressant drug discovery.

Inflammatory bowel diseases are characterized by chronic intestinal inflammation and alterations in the gut microbiota composition. Bacteroides fragilis, which secretes outer membrane vesicles (OMVs) with polysaccharide A (PSA), can moderate the inflammatory response and possibly alter the microbiota composition. In this study, we created a murine model of chronic sodium dextran sulfate (DSS)-induced intestinal colitis and treated it with B. fragilis OMVs. We monitored the efficiency of OMV therapy by determining the disease activity index (DAI) and performing histological examination (HE) of the intestine before and after vesicle exposure. We also analyzed the microbiota composition using 16S rRNA gene sequencing. Finally, we evaluated the volatile compound composition in the animals' stools by HS-GC/MS to assess the functional activity of the microbiota. We observed more effective intestinal repair after OMV treatment according to the DAI and HE. A metabolomic study also revealed changes in the functional activity of the microbiota, with a predominance of phenol and pentanoic acid in the control group compared to the group treated with DSS and the group treated with OMVs (DSS OMVs). We also observed a positive correlation of these metabolites with Saccharibacteria and Acetivibrio in the control group, whereas in the DSS group, there was a negative correlation of phenol and pentanoic acid with Lactococcus and Romboutsia. According to the metabolome and sequencing data, the microbiota composition of the DSS-treated OMV group was intermediate between that of the control and DSS groups. OMVs not only have an anti-inflammatory effect but also contribute to the recovery of the microbiota composition.IMPORTANCEBacteroides fragilis vesicles contain superficially localized polysaccharide A (PSA), which has unique immune-modulating properties. Isolated PSA can prevent chemically induced colitis in a murine model. Outer membrane vesicles (OMVs) also contain digestive enzymes and volatile metabolites that can complement the anti-inflammatory properties of PSA. OMVs showed high therapeutic activity against sodium dextran sulfate-induced colitis, as confirmed by histological assays. 16S rRNA sequencing of fecal samples from different inflammatory stages, supplemented with comprehensive metabolome analysis of volatile compounds conducted by HS-GC/MS, revealed structural and functional alterations in the microbiota composition under the influence of OMVs. Correlation analysis of the OMV-treated and untreated experimental animal groups revealed associations of phenol and pentanoic acid with Lactococcus, Romboutsia, Saccharibacteria, and Acetivibrio.

Background/Objectives: One of the hallmarks of Alzheimer’s disease (AD) is the accumulation of aggregated beta-amyloid (Aβ) protein in the form of senile plaques within brain tissue. Senile plaques contain various post-translational modifications of Aβ, including prevalent isomerization of Asp7 residue. The Asp7 isomer has been shown to exhibit increased neurotoxicity and induce amyloidogenesis in brain tissue of transgenic mice. The toxicity of Aβ peptides may be partly mediated by their structure and morphology. In this respect, in this study we analyzed the structural and aggregation characteristics of the Asp7 isoform of Aβ42 and compared them to those of synthetic Aβ42. We also investigated the effects of intracerebroventricular (i.c.v.) administration of these peptides, a method often used to induce AD-like symptoms in rodent models. Methods: Atomic force microscopy (AFM) was conducted to compare the morphological and aggregation properties of Aβ42 and Asp7 iso-Aβ42. The effects of i.c.v. stereotaxic administration of the proteins were assessed via behavioral analysis and reactive oxygen species (ROS) estimation in vivo using a scanning ion-conductance microscope with a confocal module. Results: AFM measurements revealed structural differences between the two peptides, most notably in their soluble toxic oligomeric forms. The i.c.v. administration of Asp7 iso-Aβ42 induced spatial memory deficits in rats and elevated oxidative stress levels in vivo, suggesting a potential of ROS in the pathogenic mechanism of the peptide. Conclusions: The findings support the further investigation of Asp7 iso-Aβ42 in translational research on AD and suggest its involvement in neurodegenerative processes.

Protein (eggwhite) and chitosan aerogel microparticles characterized by low density, developed morphology, high specific surface area, high porosity, large volume, and small pore diameter, have been obtained. Particle size distribution curves were obtained by laser diffraction, from which the number average and aerodynamic diameters were calculated. The aerodynamic diameter of all of the obtained biopolymer aerogels lies in the range required for targeted delivery of active pharmaceutical ingredients (APIs) to the olfactory region of the nasal cavity. Experimental studies were performed to introduce the “melatonin” API in the pores of biopolymer aerogels at the solvent replacement and supercritical adsorption steps. The mass fractions of APIs in the resulting biopolymer aerogel–API pharmaceutical composites were determined by high-performance liquid chromatography. An X-ray powder diffraction analysis showed that API was present in pharmaceutical compositions mainly in the amorphous state. The results of in vivo experimental studies showed that in the case of intranasal administration of both biopolymer aerogel–API composites, the maximum concentration of API in brain tissues is reached already after 30 min. This proves that the obtained biopolymer aerogels based on protein (eggwhite) and chitosan are promising for use as API carrier matrices in the development of nasal drug delivery systems.

Electroconvulsive therapy (ECT) is an effective treatment method for depression therapy. It produces a number of biological effects, including neurotrophic factors regulation. In the present paper, we investigated the ECT response in depressed rats subjected to the variable frequency ultrasound (20–45 kHz) and examined the contribution of brain-derived neurotrophic factor (BDNF) expression changes to the observed effects. The obtained results reflect the therapeutic potential of ECT for the treatment of depressive-like state in rodents and indicate the role of BDNF in these processes. In future research, it is necessary to investigate the relationship between neurotrophin and structural changes and to study other neurotrophic biomarkers that may be associated with the development of depression-like state and the therapy response.

Natural products (NPs) often act as sources of CNS-active agents and provide inspiration for the development of synthetic molecules that incorporate their best features. Vindeburnol (VIND; (±)-(3α,14β)-20,21-dinoreburnamenin-14-ol; developmental codes RU24722 or BC19), based on the core structure of eburnamine-vincamine alkaloids, has been extensively investigated for its biological activities. This molecule has demonstrated potential therapeutic properties in various in vivo models of CNS disorders such as multiple sclerosis, Alzheimer's disease, and depressive-like behavior. Although few clinical trials were conducted, further development of vindeburnol was abandoned. This review presents synthetic approaches to vindeburnol synthesis as well as the most complete discussion of its pharmacological effects. Studies involving vindeburnol in animal models of CNS disorders and a few human trials have been presented in separate sections. Special attention is placed on derivatives and analogs based on the vindeburnol scaffold. The interesting pharmacological profile of vindeburnol suggests that this NP-inspired compound may serve as a useful tool or structural basis for next-generation molecules in CNS drug design and discovery.

Prenatal stress (PS) affects the development and functioning of the central nervous system, but the exact mechanisms underpinning this effect have not been pinpointed yet. A promising model of PS is one based on chronic exposure of pregnant rodents to variable-frequency ultrasound (US PS), as it mimics the PS with a psychic nature that most adequately captures the human stressors in modern society. The aim of this study was to investigate the effects of US PS on the brain neurotransmitter, neuropeptide, and neurotrophic systems of newborn Wistar rats. We determined the concentration of neurotransmitters and their metabolites (serotonin, HIAA, dopamine, DOPAC, and norepinephrine), neuropeptides (α-MSH, β-endorphin, neurotensin, oxytocin, and substance P), and the neurotrophin brain-derived neurotrophic factor (BDNF) in rat brain tissues by HPLC-ED, ELISA, and multiplex ELISA. Correlation analysis and principal component analysis (PCA) were used to get a sense of the relationship between the biochemical parameters of the brain. The results demonstrated that US PS increases the concentration of serotonin (p=0.004) and DOPAC (p=0.04) in the hippocampus has no effect on the neurotransmitter systems of the frontal cortex, reduces the concentration of BDNF in the entirety of the brain of males (p=0.008), and increases the neuropeptides α-MSH (p=0.02), β-endorphin (p=0.01), oxytocin (p=0.008), and substance P (p<0.001) in the entire brain. A degree of complexity in the neurotransmitter system network in the frontal cortex and network change in the hippocampus after exposure to US PS have been observed. PCA revealed a similar pattern of neurotransmitter system interactions in the frontal cortex and hippocampus in males and females after exposure to US PS. We suggest that US PS can alter neurodevelopment, which is mediated by changes in the studied neurochemical systems that thus affect the behavioral phenotype in animals.

Получены микрочастицы аэрогеля на основе яичного белка и хитозана, характеризующиеся низкой плотностью, развитой морфологией и высокой удельной площадью поверхности, высокой пористостью, большим объемом и малым диаметром пор. Методом лазерной дифракции получены кривые распределения частиц по размерам, из которых были рассчитаны среднечисленный и аэродинамический диаметры. Аэродинамический диаметр всех полученных биополимерных аэрогелей лежит в диапазоне, необходимом для осуществления адресной доставки активных фармацевтических ингредиентов (АФИ) в обонятельную область носовой полости. Проведены экспериментальные исследования по внедрению АФИ «мелатонин» в поры биополимерных аэрогелей на стадии замены растворителя и методом сверхкритической адсорбции. Методом высокоэффективной жидкостной хроматографии определены массовые доли АФИ в полученных фармацевтических композициях «биополимерный аэрогель — АФИ». Методом рентгенофазового анализа показано, что АФИ в фармацевтических композициях присутствует преимущественно в аморфном состоянии. Результаты экспериментальных исследований in vivo показали, что в случае интраназального введения обеих композиций «биополимерный аэрогель — АФИ» максимальная концентрация АФИ в тканях мозга достигается уже через 30 мин. Это доказывает, что полученные биополимерные аэрогели на основе белка и хитозана перспективны для использования в качестве матриц-носителей АФИ при разработке назальных систем их доставки. Protein (egg white) and chitosan aerogel microparticles characterized by low density, developed morphology and high specific surface area, high porosity, large volume and small pore diameter, were obtained. Using the laser diffraction method, particle size distribution curves were obtained, from which the average number and aerodynamic diameters were calculated. The aerodynamic diameter of all obtained biopolymer aerogels lies in the range required for targeted delivery of active pharmaceutical ingredients (APIs) to the olfactory region of the nasal cavity. Experimental studies have been carried out on the introduction of API «melatonin» into the pores of biopolymer aerogels at the stages of solvent replacement and supercritical adsorption. Mass fractions of API in the resulting pharmaceutical compositions «biopolymer aerogel — API» were determined by high-performance liquid chromatography. X-ray powder diffraction showed that API in pharmaceutical compositions is present mainly in the amorphous state. The results of in vivo experimental studies showed that in the case of intranasal administration of both «biopolymer aerogel — API» compositions, the maximum concentration of API in brainтtissues is reached after 30 minutes. This proves that the resulting biopolymer aerogels based on protein (egg white) and chitosan are promising for use as API carrier matrices in the development of nasal drug delivery systems.

The development of animal models of mental disorders is an important task, since such models are useful for studying the neurobiological mechanisms of psychopathologies and for trial of new therapeutic drugs. One way to model pathologies of the nervous system is to impair fetal neurodevelopment through stress of the pregnant future mother, or prenatal stress. The use of variable frequency ultrasound in rodents is a promising method of imitating psychological stress, to which women in modern society are most often subjected. The aim of our study was to investigate the effect of prenatal stress induced by exposure to variable frequency ultrasound (US PS) throughout the gestational period on the adult rat offspring, namely to identify features of behavioral alterations and neurochemical brain parameters that can be associated with certain mental disorders in humans, to determine the possibility of creating a new model of psychopathology. Our study included a study of some behavioral characteristics of male and female rats in the elevated plus maze, open field test, object recognition test, social interaction test, sucrose preference test, latent inhibition test, Morris water maze, forced swimming test, acoustic startle reflex and prepulse inhibition tests. We also determined the activity of the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems in the hippocampus and frontal cortex by HPLC-ED. Concentration of norepinephrine, dopamine, DOPAC, serotonin, and HIAA, as well as DOPAC/dopamine and HIAA/serotonin ratios were determined. A correlation analysis of behavioral and neurochemical parameters in male and female rats was performed based on the data obtained. The results of the study showed that US PS altered the behavioral phenotype of the rat offspring. US PS increased the level of anxious behavior, impaired orientation-research behavior, increased grooming activity, decreased the desire for social contacts, shifted behavioral reactions from social interaction to interaction with inanimate objects, impaired latent inhibition, and decreased the startle reflex. US PS activated the serotonergic, dopaminergic, and noradrenergic neurotransmitter systems of the rat frontal cortex and hippocampus. A correlation between neurochemical and behavioral parameters was revealed. Our study showed that US PS leads to a certain dysfunction on behavioral and neurochemical levels in rats that is most closely associated with symptoms of schizophrenia or autism. We hypothesize that this could potentially be an indicator of face validity for a model of psychopathology based on neurodevelopmental impairment.

The search for potential effective antidepressants with minimal side effects is necessary. Peptides are possible applicants for this role. We investigated the antidepressant effect of neuropeptide Y (NY), alone and in combination with clomipramine, in models of acute and chronic stress induced by ultrasound of variable frequencies. Rats were divided into the following groups: the control group, stress group, and stress groups with intranasal administration of NY (100 μg/kg) or clomipramine (7.5 mg/kg), or their combination. Rat behavior was evaluated using a sucrose preference test and forced swimming test in an acute stress model, and a sucrose preference test, forced swimming test, social interaction test, open field test, and Morris water maze test in a chronic stress model. The results of our experiment demonstrated a protective effect of intranasal NY in a model of acute stress, which was comparable to the antidepressant effect of clomipramine. When the same dose was chronically administered, NY also demonstrated an antidepressant action, although expressed in a lesser degree than clomipramine. The combination of NY and clomipramine was much less effective in the chronic stress paradigm compared to the separated drug administration, but was just as effective in the acute stress paradigm. Until now, there was no convincing evidence for the efficacy of the chronic administration of neuropeptide Y; we demonstrated its effectiveness in the animal model of depressive-like behavior. However, our hypothesis that neuropeptide Y can enhance the effect of a classical antidepressant was not confirmed.

Objectives: In the current study, we compared the effects of a single intranasal administration of clomipramine with effects of four neuropeptides, melatonin, oxytocin, orexin, and neuropeptide Y, to compare them in an acute stress model. Methods: The anti-stress effect was evaluated in the sucrose preference and forced swimming tests. Serum corticosterone level in rats was measured to evaluate the stress response. Results: Neuropeptide Y reduced immobilization time in the Porsolt test and decreased corticosterone levels, but increased the anhedonia. Orexin had no positive effect on animal behavior, but decreased corticosterone levels. Oxytocin decreased immobilization time, maintained anhedonia at the level of control, but did not affect corticosterone levels. Melatonin demonstrated no positive effects in any of the tests. Conclusion: The intranasal administered neuropeptide Y could be a promising compound for the treatment of stress disorders.

In this study, we identified the optimal time frame for the development of signs of beta-amyloid-induced Alzheimer's disease using behavioral tests. It was shown that significant cognitive impairments in males were observed 8 weeks after injection of the beta-amyloid peptide.

Mental disorders represent common brain diseases characterized by substantial impairments of social and cognitive functions. The neurobiological causes and mechanisms of psychopathologies still have not been definitively determined. Various forms of brain proteinopathies, which include a disruption of protein conformations and the formation of protein aggregates in brain tissues, may be a possible cause behind the development of psychiatric disorders. Proteinopathies are known to be the main cause of neurodegeneration, but much less attention is given to the role of protein impairments in psychiatric disorders' pathogenesis, such as depression and schizophrenia. For this reason, the aim of this review was to discuss the potential contribution of protein illnesses in the development of psychopathologies. The first part of the review describes the possible mechanisms of disruption to protein folding and aggregation in the cell: endoplasmic reticulum stress, dysfunction of chaperone proteins, altered mitochondrial function, and impaired autophagy processes. The second part of the review addresses the known proteins whose aggregation in brain tissue has been observed in psychiatric disorders (amyloid, tau protein, α-synuclein, DISC-1, disbindin-1, CRMP1, SNAP25, TRIOBP, NPAS3, GluA1, FABP, and ankyrin-G).