Chronic Ultrasound Prenatal Stress Altered the Brain's Neurochemical Systems in Newborn Rats.

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, ß-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), ß-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.

Ultrasound-Induced Prenatal Stress: New Possibilities for Modeling Mental Disorders.

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.

Inflammatory biomarkers and lipid metabolism parameters in women with mild cognitive impairment and dementia.

The detection of specific markers of dementia and mild cognitive decline (MCI) could be the key to disease prevention and forehanded treatment. Female gender is one of the major risk factor for dementia. The aim of our study was to compare serum concentration of some factors related to lipid metabolism and the immune system in patients with MCI and dementia. The study was performed on women >65 years old: controls (n = 75), diagnosed with dementia (n = 73) and MCI (n = 142). Patients were evaluated using Mini-Mental State Examination, Clock Drawing Test and Montreal Cognitive Assessment scales in the period 2020-2021. The level of Apo A1 and HDL was significantly decreased in patients with dementia; the level of Apo A1 was also decreased in MCI. EGF, eotaxin-1, GRO-α, and IP-10 were elevated in patients with dementia compared to the controls. IL-8, MIP-1ß, sCD40L, and TNF-α levels were decreased in MCI patients and increased in patients with dementia compared to the control. Serum VEGF levels were decreased in MCI and dementia patients in comparison with the control. We hypothesize that no single marker can indicate a neurodegenerative process. Future research should focus on identifying markers to determine possible diagnostic combinations that can reliably predict neurodegeneration.

Localized Increased Permeability of Blood-Brain Barrier for Antibody Conjugates in the Cuprizone Model of Demyelination.

The development of new neurotherapeutics depends on appropriate animal models being chosen in preclinical studies. The cuprizone model is an effective tool for studying demyelination and remyelination processes in the brain, but blood-brain barrier (BBB) integrity in the cuprizone model is still a topic for debate. Several publications claim that the BBB remains intact during cuprizone-induced demyelination; others demonstrate results that could explain the increased BBB permeability. In this study, we aim to analyze the permeability of the BBB for different macromolecules, particularly antibody conjugates, in a cuprizone-induced model of demyelination. We compared the traditional approach using Evans blue injection with subsequent dye extraction and detection of antibody conjugates using magnetic resonance imaging (MRI) and confocal microscopy to analyze BBB permeability in the cuprizone model. First, we validated our model of demyelination by performing T2-weighted MRI, diffusion tensor imaging, quantitative rt-PCR to detect changes in mRNA expression of myelin basic protein and proteolipid protein, and Luxol fast blue histological staining of myelin. Intraperitoneal injection of Evans blue did not result in any differences between the fluorescent signal in the brain of healthy and cuprizone-treated mice (IVIS analysis with subsequent dye extraction). In contrast, intravenous injection of antibody conjugates (anti-GFAP or non-specific IgG) after 4 weeks of a cuprizone diet demonstrated accumulation in the corpus callosum of cuprizone-treated mice both by contrast-enhanced MRI (for gadolinium-labeled antibodies) and by fluorescence microscopy (for Alexa488-labeled antibodies). Our results suggest that the methods with better sensitivity could detect the accumulation of macromolecules (such as fluorescent-labeled or gadolinium-labeled antibody conjugates) in the brain, suggesting a local BBB disruption in the demyelinating area. These findings support previous investigations that questioned BBB integrity in the cuprizone model and demonstrate the possibility of delivering antibody conjugates to the corpus callosum of cuprizone-treated mice.

Alteration of Blood Immune Biomarkers in MCI Patients with Different APOE Genotypes after Cognitive Training: A 1 Year Follow-Up Cohort Study.

Many studies aim to detect the early phase of dementia. One of the major ways to achieve this is to identify corresponding biomarkers, particularly immune blood biomarkers. The objective of this study was to identify such biomarkers in patients with mild cognitive impairment (MCI) in an experiment that included cognitive training. A group of patients with MCI diagnoses over the age of 65 participated in the study (n = 136). Measurements of cognitive functions (using the Mini-Mental State Examination scale and Montreal Cognitive Assessment) and determination of 27 serum biomarkers were performed twice: on the first visit and on the second visit, one year after the cognitive training. APOE genotypes were also determined. Concentrations of EGF (F = 17; p = 0.00007), Eotaxin (F = 7.17; p = 0.008), GRO (F = 13.42; p = 0.0004), IL-8 (F = 8.16; p = 0.005), MCP-1 (F = 13.46; p = 0.0001) and MDC (F = 5.93; p = 0.016) increased after the cognitive training in MCI patients. All these parameters except IL-8 demonstrated a weak correlation with other immune parameters and were poorly represented in the principal component analysis. Differences in concentrations of IP-10, FGF-2, TGFa and VEGF in patients with MCI were associated with APOE genotype. Therefore, the study identified several immune blood biomarkers that could potentially be associated with changes in cognitive function.

Antibodies against N-Methyl D-Aspartate Receptor in Psychotic Disorders: A Systematic Review.

OBJECTIVE: The objective of this study was to provide comprehensive evidence synthesis including all available up-to-date data about the prevalence of N-methyl D-aspartate receptor (NMDAR) antibodies (ABs) in psychotic patients in order to evaluate the clinical relevance of ABs as well as to specify potential explanations of the heterogeneity of the findings and determine areas for further research. METHODS: A literature search was conducted using the PubMed/Medline, Web of Knowledge, and Scopus databases. RESULTS: Forty-seven studies and 4 systematic reviews (including 2 meta-analyses) were included in the present review. Studies that used cell-based assays (CBAs) provided heterogeneous results on AB prevalence, obviously depending on the type of detection assay and sample characteristics. Improvement of AB detection methods is necessary to determine the real prevalence of ABs across different groups of patients and healthy people. Live CBAs seem to have better sensitivity but probably poorer specificity than fixed CBAs. Moreover, some links between AB-positive status and acute symptoms are possible. A small amount of data on immunotherapy in AB-positive patients raises the possibility of its effectiveness but obviously require further research. CONCLUSIONS: NMDAR ABs are definitely present in a subset of psychotic patients. NMDAR ABs might shape psychosis and underlie some symptoms, and immunotherapy might be regarded as a treatment option for patients failing to respond to other therapies.

Protein Misfolding and Aggregation in the Brain: Common Pathogenetic Pathways in Neurodegenerative and Mental Disorders.

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).

Neurobiological Highlights of Cognitive Impairment in Psychiatric Disorders.

This review is focused on several psychiatric disorders in which cognitive impairment is a major component of the disease, influencing life quality. There are plenty of data proving that cognitive impairment accompanies and even underlies some psychiatric disorders. In addition, sources provide information on the biological background of cognitive problems associated with mental illness. This scientific review aims to summarize the current knowledge about neurobiological mechanisms of cognitive impairment in people with schizophrenia, depression, mild cognitive impairment and dementia (including Alzheimer's disease).The review provides data about the prevalence of cognitive impairment in people with mental illness and associated biological markers.

Brain Metabolic Profile after Intranasal vs. Intraperitoneal Clomipramine Treatment in Rats with Ultrasound Model of Depression.

BACKGROUND: Molecular mechanisms of depression remain unclear. The brain metabolome after antidepressant therapy is poorly understood and had not been performed for different routes of drug administration before the present study. Rats were exposed to chronic ultrasound stress and treated with intranasal and intraperitoneal clomipramine. We then analyzed 28 metabolites in the frontal cortex and hippocampus. METHODS: Rats' behavior was identified in such tests: social interaction, sucrose preference, forced swim, and Morris water maze. Metabolic analysis was performed with liquid chromatography. RESULTS: After ultrasound stress pronounced depressive-like behavior, clomipramine had an equally antidepressant effect after intranasal and intraperitoneal administration on behavior. Ultrasound stress contributed to changes of the metabolomic pathways associated with pathophysiology of depression. Clomipramine affected global metabolome in frontal cortex and hippocampus in a different way that depended on the route of administration. Intranasal route was associated with more significant changes of metabolites composition in the frontal cortex compared to the control and ultrasound groups while the intraperitoneal route corresponded with more profound changes in hippocampal metabolome compared to other groups. Since far metabolic processes in the brain can change in many ways depending on different routes of administration, the antidepressant therapy should also be evaluated from this point of view.

Glioma Cell and Astrocyte Co-cultures As a Model to Study Tumor-Tissue Interactions: A Review of Methods.

Astrocytes are a dominant cell type that envelopes the glioma bed. Typically, that is followed by formation of contacts between astrocytes and glioma cells and accompanied by change in astrocyte phenotype, a phenomenon known as a 'reactive astrogliosis.' Generally considered glioma-promoting, astrocytes have many controversial peculiarities in communication with tumor cells, which need thorough examination in vitro. This review is devoted to in vitro co-culture studies of glioma cells and astrocytes. Firstly, we list several fundamental works which allow understanding the modalities of co-culturing. Cell-to-cell interactions between astrocytes and glioma cells, the roles of astrocytes in tumor metabolism, and glioma-related angiogenesis are reviewed. In the review, we also discuss communications between glioma stem cells and astrocytes. Co-cultures of glioma cells and astrocytes are used for studying anti-glioma treatment approaches. We also enumerate surgical, chemotherapeutic, and radiotherapeutic methods assessed in co-culture experiments. In conclusion, we underline collisions in the field and point out the role of the co-cultures for neurobiological studies.

Beta-Amyloid and Its Asp7 Isoform: Morphological and Aggregation Properties and Effects of Intracerebroventricular Administration.

BACKGROUND/OBJECTIVES: One of the hallmarks of Alzheimer's disease (AD) is the accumulation of aggregated beta-amyloid (Aß) protein in the form of senile plaques within brain tissue. Senile plaques contain various post-translational modifications of Aß, 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 Aß 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 Aß42 and compared them to those of synthetic Aß42. 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 Aß42 and Asp7 iso-Aß42. 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-Aß42 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-Aß42 in translational research on AD and suggest its involvement in neurodegenerative processes.

BDNF, DRD4, and HTR2A Gene Allele Frequency Distribution and Association with Mental Illnesses in the European Part of Russia.

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.

Targeted delivery of liposomal nanocontainers to the peritumoral zone of glioma by means of monoclonal antibodies against GFAP and the extracellular loop of Cx43.

The selectivity of PEGylated immunoliposomes based on monoclonal antibodies against GFAP and the E2 extracellular loop of connexin 43 (MAbE2Cx43) with respect to the focus of a glioma was estimated in experiments on animals with intracranial C6 glioma. Stealth immunoliposomes were labeled with 2 alternative labels, a fluorescent (Dil C18) and a paramagnetic (Gd-DTPA) one. Fluorescent-labeled liposomal nanocontainers were detected at the periphery of the glioma, where the target antigens were overexpressed, 48 hours after injection. Dynamic T1 MRI of rats injected with paramagnetic immunoliposomes carrying MAbE2Cx43 showed distinct accumulation of the paramagnetic contrast agent at the periphery of the glioma, which began 6 hours after administration. These data suggest that immunoliposomal nanocontainers based on antibodies against GFAP and the E2 extracellular fragment of connexin 43 are suitable for targeted delivery of diagnostic and therapeutic drugs to the peritumoral invasion zone of high-grade gliomas. FROM THE CLINICAL EDITOR: PEGylated immunoliposomes based on monoclonal antibodies against GFAP and the E2 extracellular loop of connexin 43 were investigated in animals with intracranial C6 glioma. These immunoliposomal nanocontainers were found suitable for targeted delivery of diagnostic and therapeutic drugs to the peritumoral invasion zone of high-grade gliomas.

Intranasal neuropeptide Y is most effective in some aspects of acute stress compared to melatonin, oxytocin and orexin.

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.

Preparation of Protein Aerogel Particles for the Development of Innovative Drug Delivery Systems.

The research was oriented towards the preparation of aerogel particles based on egg white and whey protein isolate using various dispersion methods: dripping, spraying, and homogenization. Based on the results of analytical studies, the most appropriate samples were selected to obtain aerogels loaded with the drug. The results of the experimental research were used to study methods for obtaining nasal drug delivery systems based on aerogels. Protein aerogels were obtained by thermal gelation followed by supercritical drying. The obtained particles of protein aerogels have a specific surface area of up to 350 m2/g with a pore volume of up to 2.9 cm3/g, as well as a porosity of up to 95%. The results of experimental studies have shown that changing the dispersion method makes it possible to control the structural characteristics of protein aerogel particles. The results of the studies were applied to obtain innovative nasal drug delivery systems for the treatment of socially significant diseases. Analytical studies were conducted to determine the amount and state of adsorbed drugs in protein aerogel particles, as well as in vivo experiments on the distribution of clomipramine in blood plasma and brain tissue of rats to study the pharmacokinetics and bioavailability of the resulting drug-loaded protein aerogel.

Positive Effect of Cognitive Training in Older Adults with Different APOE Genotypes and COVID-19 History: A 1-Year Follow-Up Cohort Study.

(1) Background: Older people suffer from cognitive decline; several risk factors contribute to greater cognitive decline. We used acquired (COVID-19 infection) and non-modifiable (presence of APOE rs429358 and rs7412 polymorphisms) factors to study the progression of subjective cognitive impairment while observing patients for one year. Cognitive training was used as a protective factor. (2) Methods: Two groups of subjects over the age of 65 participated in the study: group with subjective cognitive decline receiving cognitive training and individuals who did not complain of cognitive decline without receiving cognitive training (comparison group). On the first visit, the concentration of antibodies to COVID-19 and APOE genotype was measured. At the first and last point (1 year later) the Mini-Mental State Examination scale and the Hospital Anxiety and Depression Scale were performed. (3) Results: COVID-19 infection did not affect cognitive function. A significant role of cognitive training in improving cognitive functions was revealed. Older adults with APOE-ε4 genotype showed no positive effect of cognitive training. (4) Conclusions: Future research should focus on cognitive dysfunction after COVID-19 in long-term follow-up. Attention to the factors discussed in our article, but not limited to them, are useful for a personalized approach to maintaining the cognitive health of older adults.

Suicide-Related Single Nucleotide Polymorphisms, rs4918918 and rs10903034: Association with Dementia in Older Adults.

Dementia has enormous implications for patients and the health care system. Genetic markers are promising for detecting the risk of cognitive impairment. We hypothesized that genetic variants associated with suicide risk might significantly increase the risk of cognitive decline because suicide in older adults is often a consequence of cognitive impairment. We investigated several single-nucleotide polymorphisms that were initially associated with suicide risk in dementia older adults and identified the APOE gene alleles. The study was performed with subjects over the age of 65: 112 patients with dementia and 146 healthy volunteers. The MMSE score was used to assess cognitive functions. Study participants were genotyped using real-time PCR (APOE: rs429358, rs7412; genes associated with suicide: rs9475195, rs7982251, rs2834789, rs358592, rs4918918, rs3781878, rs10903034, rs165774, rs16841143, rs11833579 rs10898553, rs7296262, rs3806263, and rs2462021). Genotype analysis revealed the significance of APOEε4, APOEε2, and rs4918918 (SORBS1) when comparing dementia and healthy control groups. The association of APOEε4, APOEε2, and rs10903034 (IFNLR1) with the overall MMSE score was indicated. The study found an association with dementia of rs4918918 (SORBS1) and rs10903034 (IFNLR1) previously associated with suicide and confirmed the association of APOEε4 and APOEε2 with dementia.

Proteomic dataset: Profiling of glioma C6 and astrocytes rat cell lines before and after co-cultivation.

Human multiforme glioblastoma is characterized by an unfavorable prognosis, low survival rate and extremely limited possibilities for therapy. Rat C6 glioma is an experimental model for the study of glioblastoma growth and invasion. It has been shown that the growth and development of the tumor is accompanied by changes in the surrounding normotypic tissues [1]. These changes create a favorable environment for the development of the tumor and give it an evolutionary advantage [2]. Description of changes occurring in normotypic cells of the body upon their contact with tumor cells is of great interest. We have grown C6 glioma cells and rat astrocytes, as well as astrocyte cells co-cultured together with C6 glioma. We performed proteome-wide LC-MS analysis of these experimental groups. The data includes LC-MS/MS raw files and exported MaxQuant and ProteinPilot search results with fasta. Dataset published in the PRIDE repository project accession PXD026776.

Plasma Neurotrophic Factor Levels are not Associated with the Severity of Depression: Prospective Pilot Study.

INTRODUCTION: Depression is one of the most common mental illnesses. Impaired neurogenesis is observed in depression. Biomarkers of impaired neurogenesis in depression can act as a useful objective and diagnostic and prognostic tool to determine the severity of depression. AIM: To study the concentration of biochemical indicators in the blood that may be involved in the pathogenesis of depression and their intercorrelations, and to determine any associations between the concentrations of biochemical indicators and severity of depressive symptoms. METHODS: We determined the plasma concentrations of serotonin, dopamine, and neurotrophic factors involved in neurogenesis (BDNF, CDNF and neuropeptide Y) using enzyme immunoassay and mass spectrometry in depressed patients (n=22) and healthy controls (n=16) matched by socio-demographic parameters. All participants were assessed using the Hamilton Depression Scale (HAMD), the Generalized Anxiety Disorder Questionnaire (GAD-7), and the Center for Epidemiologic Studies Depression Scale (CES-D) to enter the study. The standard cut-offs for the CES-D and GAD-7 scales were used to confirm the presence or absence of depression and anxiety. RESULTS: The concentrations of serotonin, dopamine, BDNF, CDNF, and neuropeptide Y in plasma did not differ between the groups and was not found to be associated with the scores on the scales. Positive correlations were found between the concentration of neuropeptide Y and serotonin, BDNF, and CDNF in blood plasma. CONCLUSIONS: Plasma concentrations of biomarkers related to the pathophysiology of depression did not correlate with the severity of its symptoms.

Study of possibility of cell recognition in brain tumors.

The brain has an exceptionally high requirement for energy metabolism, with glucose serving as the exclusive energy source. Cancers, including glioblastoma, have a high glucose uptake and rely on aerobic glycolysis for energy metabolism. The alternation of high-efficiency oxidative phosphorylation to a low-efficiency aerobic glycolysis pathway (Warburg effect) provides macromolecules for biosynthesis and proliferation. Current research indicates that the specific metabolism in the tumor tissue and normal brain tissue in the glioma allows the use of 5-aminolevulinic acid (5 ALA)-induced protoporphyrin IX (PpIX) and methylene blue (MB) to monitor and correct the development of the tumor. The focus is on the detection of the differences between tumor cells and tumor-associated macrophages/microglia using spectroscopic and microscopic methods, based on the fluorescent signals and the difference in the drug accumulation of photosensitizers (PSs). Since 5 ALA has long been used effectively in the clinic for fluorescent surgical navigation, it was employed as an agent to identify the localization of tumor tissue and study its composition, particularly tumor and immune cells (macrophages), which have also been shown to actively accumulate PpIX. However, since PpIX is photodynamically active, it can be considered effective as the main target of tumor tissue for further successful photodynamic therapy. MB was employed to visualize resident microglia, which is important for their activation/deactivation to prevent the reprogramming of the immune cells by the tumor. Thus, using two drugs, it is possible to prevent crosstalk between tumor cells and the immune cells of different geneses.