Exposure to ionizing radiation during manned deep space missions to Mars could lead to functional impairments of the central nervous system, which may compromise the success of the mission and affect the quality of life for returning astronauts. Along with radiation-induced changes in cognitive abilities and emotional status, the effects of increased motor activity were observed. The mechanisms behind these phenomena still remain unresolved. We conducted a study on grip strength, locomotor activity and intrasession habituation to novelty in 5-month-old rats after exposure to radiation (combined 0.4 Gy gamma-rays and 0.14 Gy 12C nuclei). At the same time, we carried out neurochemical and molecular analysis of the nucleus accumbens (NAc) and the dorsal striatum (dST). The study revealed radiation-induced hyperlocomotion and enhanced habituation. It also showed an increase in choline concentration and a decreased in 5-hydroxyindoleacetic acid concentration in the NAc after irradiation. In addition to this, a down-regulation of syntaxin 1A in NAc and dST as well as up-regulation α-synuclein in NAc were observed. The obtained data indicate both the damaging effect of irradiation on striatum tissues and the initiation of neuronal/axonal regeneration processes. It is hypothesized that the increase in choline concentration in NAc and the decreased content of syntaxin 1A in dST may be the part of the mechanism responsible for the radiation-induced hyperlocomotion.

Neuroinflammation can be an important factor of many disorders in central nervous system (CNS) including cognitive dysfunction, affective disorders, and addictive behavior associated with prenatal alcohol exposure and presented in early adulthood. In this study we used an experimental rodent model of prenatal alcohol (PA) exposure (consumption of a 10

In orbital and ground-based experiments, it has been demonstrated that ionizing radiation (IR) can stimulate the locomotor and exploratory activity of rodents, but the underlying mechanism of this phenomenon remains undisclosed. Here, we studied the effect of combined IR (0.4 Gy γ-rays and 0.14 Gy carbon-12 nuclei) on the locomotor and exploratory activity of rats, and assessed the sensorimotor cortex volume by magnetic resonance imaging-based morphometry at 1 week and 7 months post-irradiation. The sensorimotor cortex tissues were processed to determine whether the behavioral and morphologic effects were associated with changes in neurotrophin content. The irradiated rats were characterized by increased locomotor and exploratory activity, as well as novelty-seeking behavior, at 3 days post-irradiation. At the same time, only unirradiated rats experienced a significant decrease in the sensorimotor cortex volume at 7 months. While there were no significant differences at 1 week, at 7 months, the irradiated rats were characterized by higher neurotrophin-3 and neurotrophin-4 content in the sensorimotor cortex. Thus, IR prevents the age-associated decrease in the sensorimotor cortex volume, which is associated with neurotrophic and neurogenic changes. Meanwhile, IR-induced increases in locomotor activity may be the cause of the observed changes.

Affective disorders, including anxiety and depression, developed in adult offspring of the mothers who consumed alcohol during pregnancy could be associated with an imbalance in neuroimmune factors in the amygdala (corpus amygdaloideum) resulted in impaired emotional stimulus processing. The aim of this study was to compare the content of cytokines TNF-α, IL-1α, IL-1β, IL-10, and IL-17 in the amygdala of adult female rats exposed to alcohol in utero and control rats. Cytokine levels were evaluated using a multiplex immunoassay system; mRNA expression was investigated using a real-time reverse transcription-polymerase chain reaction (RT-qPCR) assay. Prenatal alcohol exposure led to the increase in the content of TNF-α and IL-1β without significant changes in the mRNA expression level. Our data suggest that ethanol exposure to the fetus during pregnancy can result in long-term alterations in the content of the key neuroinflammatory factors in the amygdala, which in turn can be a risk factor for affective disorders in the adulthood.

Earlier we showed the pro-cognitive effect of low doses of combined irradiation (including heavy charged particles) on Wistar rats. In the present work we studied the effect of irradiation (gamma-rays, 0.24 Gy; carbon-12, 0.18 Gy, 400 MeV/nucleon) on the course of neurodegenerative process using Tau P301S and 5xFAD transgenic mice lines, experimental models of Alzheimer’s disease. Irradiation led to an increase in pro- and anti-inflammatory cytokines and chemokines (IL-2, IL-6, IL-10, KC) in Tau P301S mice, but not in 5xFAD. At the same time, only the Tau P301S line was found to exhibit radiation-induced improvement in spatial learning.

Galactic cosmic rays (GCR) pose a serious threat to astronauts' health during deep space missions. The possible functional alterations of the central nervous system (CNS) under GCR exposure can be critical for mission success. Despite the obvious negative effects of ionizing radiation, a number of neutral or even positive effects of GCR irradiation on CNS functions were revealed in ground-based experiments with rodents and primates. This review is focused on the GCR exposure effects on emotional state and cognition, emphasizing positive effects and their potential mechanisms. We integrate these data with GCR effects on adult neurogenesis and pathological protein aggregation, forming a complete picture. We conclude that GCR exposure causes multidirectional effects on cognition, which may be associated with emotional state alterations. However, the irradiation in space-related doses either has no effect or has performance enhancing effects in solving high-level cognition tasks and tasks with a high level of motivation. We suppose the model of neurotransmission changes after irradiation, although the molecular mechanisms of this phenomenon are not fully understood.

Alcohol experienced during gestation is associated with the development of neurodevelopmental and neuropsychiatric dysfunctions, as well as addictive behavior in the offspring. However, the biological basis of these effects remains poorly understood. Taking into account that the extrahypothalamic corticotropin-releasing factor (CRF) system plays an important role in regulation of the negative emotional state produced by alcohol abuse and withdrawal, the present study was aimed at investigating: 1) the effect of prenatal alcohol exposure (PA) on voluntary alcohol drinking (free choice 24 hours/day) or intermittent (“drinking in the dark”) regimen in adult Wistar rats; 2) differences in the basal gene expression levels of CRF and CRF-R1 in amygdala of adult PA and control rats; and 3) the effect of voluntary alcohol drinking on the above mRNA levels. PA males displayed a significantly greater voluntary alcohol intake than control males as observed by both drinking paradigms. 24 hours after the first withdrawal episode, PA males demonstrated a higher level of anxiety in the light-dark box test. No differences were found between PA and control females. Basal amygdalar CRF and CRFR1 mRNA levels did not differ between PA and control rats of both sexes. No difference was observed in the amygdalar CRF and CRFR1 mRNA levels after alcohol drinking in PA and control males. Conversely, the CRF mRNA levels in amygdala of PA female rats decreased under the action of alcohol consumption, compared to control female rats. The results show that the PA effect on future alcohol-related behavior is sex-specific, but do not support the hypothesis that changes in CRF and CRFR1 mRNA levels in amygdala may be responsible for high alcohol intake in males.

Space radiation, presented primarily by high-charge and -energy particles (HZEs), has a substantial impact on the central nervous system (CNS) of astronauts. This impact, surprisingly, has not only negative but also positive effects on CNS functions. Despite the fact that the mechanisms of this effect have not yet been elucidated, several studies indicate a key role for monoaminergic networks underlying these effects. Here, we investigated the effects of acute irradiation with 450 MeV/n carbon (12C) nuclei at a dose of 0.14 Gy on Wistar rats; a state of anxiety was accessed using a light–dark box, spatial memory in a Morris water maze, and the dynamics of monoamine metabolism in several brain morphological structures using HPLC. No behavioral changes were observed. Irradiation led to the immediate suppression of dopamine turnover in the prefrontal cortex, hypothalamus, and striatum, while a decrease in the level of norepinephrine was detected in the amygdala. However, these effects were transient. The deferred effect of dopamine turnover increase was found in the hippocampus. These data underscore the ability of even low-dose 12C irradiation to affect monoaminergic networks. However, this impact is transient and is not accompanied by behavioral alterations.

Disruption of normal epigenetic reprogramming during the prenatal period under the influence of exogenous factors affects fetus development and adult phenotype formation. The mechanisms through which determinants, such as maternal alcohol intake, contribute to the formation of an alcohol-vulnerable phenotype later in life still remain unclear. In this paper, we suggest that alteration in the reinforcing properties of ethanol in prenatally alcohol-exposed subjects may be associated with transcriptional dysregulation of the brain opioid receptor genes. We compared voluntary alcohol intake and levels of mRNA coding for μ- (MOP) and κ-opioid (KOP) receptors in the mesolimbic areas of adult male offspring of the female Wistar rats having received 10% ethanol as the only source of liquid throughout pregnancy or water (control). We found that prenatally alcohol exposed rats had higher alcohol preference on PND60 (free-choice paradigm) and lower mRNA expression for both MOP and KOP in the midbrain compared to the control. This suggests a potential link between prenatal alcohol, dysfunction of the brain opiate system and adult vulnerability for alcohol use disorder.

Maternal alcohol consumption is one of the strong predictive factors of alcohol use and consequent abuse; however, investigations of sex differences in response to prenatal alcohol exposure (PAE) are limited. Here we compared the effects of PAE throughout gestation on alcohol preference, state anxiety and mRNA expression of presynaptic proteins α-, β- and γ-synucleins in the brain of adult (PND60) male and female Wistar rats. Total RNA was isolated from the hippocampus, midbrain and hypothalamus and mRNA levels were assessed with quantitative RT-PCR. Compared with naïve males, naïve female rats consumed more alcohol in “free choice” paradigm (10% ethanol vs. water). At the same time, PAE produced significant increase in alcohol consumption and preference in males but not in females compared to male and female naïve groups, correspondingly. We found significantly lower α-synuclein mRNA levels in the hippocampus and midbrain of females compared to males and significant decrease in α-synuclein mRNA in these brain areas in PAE males, but not in females compared to the same sex controls. These findings indicate that the impact of PAE on transcriptional regulation of synucleins may be sex-dependent, and in males’ disruption in α-synuclein mRNA expression may contribute to increased vulnerability to alcohol-associated behavior.

BACKGROUND:Ionizing Radiation (IR) is one of the major limiting factors for human deep-space missions. Preventing IR-induced cognitive alterations in astronauts is a critical success factor. It has been shown that cognitive alterations in rodents can be inferred by alterations of a psycho- emotional balance, primarily an anxiogenic effect of IR. In our recent work, we hypothesized that the neurokinin-1 (NK1) receptor might be instrumental for such alterations.OBJECTIVE:The NK1 receptor antagonist rolapitant and the classic anxiolytic diazepam (as a comparison drug) were selected to test this hypothesis on Wistar rats.METHODS:Pharmacological substances were administered through intragastric probes. We used a battery of tests for a comprehensive ethological analysis. High-performance liquid chromatography was applied to quantify monoamines content. An analysis of mRNA expression was performed by real-time PCR. Protein content was studied by the Western blotting technique.RESULTS:Our salient finding includes no substantial changes in anxiety, locomotor activity and cognitive abilities of treated rats under irradiation. No differences were found in the content of monoamines. We discovered a synchronous effect on mRNA expression and protein content of 5- HT2a and 5-HT4 receptors in the prefrontal cortex, as well as decreased content of serotonin transporter and increased content of tryptophan hydroxylase in the hypothalamus of irradiated rats. Rolapitant affected the protein amount of a number of serotonin receptors in the amygdala of irradiated rats.CONCLUSION:Rolapitant may be the first atypical radioprotector, providing symptomatic treatment of CNS functional disorders in astronauts caused by IR.

Neurokinin‐1 receptor (NK1r) antagonists have been shown to suppress operant self‐administration of alcohol, voluntary alcohol consumption and stress‐induced reinstatement of alcohol‐seeking behaviour. Considering the long half‐life and anxiolytic‐like properties of NK1r antagonist rolapitant, we expected that it may be an effective option for reducing anxiety and alcohol motivation during early withdrawal. Voluntary alcohol intake (two‐bottles paradigm) was recorded in male Wistar rats during the three periods: 24 days (basal level), 6‐day period when rats received 5 mg·kg −1 rolapitant or vehicle and 12‐h period after repeated withdrawal episodes (alcohol cessation for 36 h). We found that upon intraperitoneal (i.p.) administration, rolapitant rapidly penetrated into specific rat brain regions – amygdala, hypothalamus and neocortex – implicated in the control of anxiety and reward. Rolapitant did not affect basal voluntary alcohol intake, but significantly suppressed anxiety‐like behaviour and alcohol consumption following withdrawal episodes. Our findings suggest that rolapitant should be further investigated as a novel treatment option for relapse prevention in alcohol‐dependent patients.

In this study, a procedure was applied to purify lipopolysaccharides from Escherichia coli based on a hot phenolic extraction protocol. The purity of the extracted lipopolysaccharides was assessed by HPLC-UV. Pyrogenic activity was determined using the Limulus Amebocyte Lysate test and used to monitor the functionality of the purified lipopolysaccharides. HPLC analysis showed a high degree of purity comparable to commercial lipopolysaccharide. Pyrogenic activity confirmed the functional activity of purified lipopolysaccharides. The presented protocol can be used to isolate lipopolysaccharides with high purity and functional activity.

The liposomal form of a new original remedy based on the preputial gland of Siberian musk has been standardized and characterized. For the preparative isolation of musk musk liposomes, an effective and scalable method of high-pressure homogenization was used. The resulting liposomal product was characterized by transmission electron microscopy, dynamic light scattering, preparative and analytical chromatography, and chromatography-mass spectrometry. A specification for the liposomal form of the extract of the prepucial gland of Siberian musk deer, including all critical indicators of the product quality, has been developed. Homogeneous dispersions of musk musk liposomes with uniform size distribution — with distribution maxima at 50 and 240 nm — were obtained. The high physical and chemical stability of the liposomal dispersion was established: the zeta potential of the obtained nanoparticles was -5...-35 mV. The degree of inclusion in the liposomes of the target components of musk musk according to gel-size chromatography and mass spectrometry for musk liposomes for steroid components and total protein was 58–75%. The developed quality indicators of the liposomal product allow for serial standardization of the manufacturing quality control and form the prerequisites for guaranteed high efficiency of the product based on the liposomal form of musk musk extract as an adaptogen of natural origin with an enhanced and pronounced effect.

The review summarizes the glutamate/GABA data in response to brain injuries of different origins. Many nonpeptide neurotransmitters have toxic effects and their metabolic impairment is closely connected with the development and propagation of the neurodegenerative process. An example is excitotoxicity resulting from hyperactivity of the N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors. One of the excitotoxins is glutamate, an excitatory agent within the central nervous system (CNS). Another neurotransmitter, γ-aminobutyric acid (GABA), is metabolically associated with glutamate and acts as an inhibitor within the CNS. The glutamate/GABA system dominates in the neocortex and is crucial in the realization of cognitive functions in animals and human creative activity. Disbalance in this system is a key factor in the development of psychiatric and neurodegenerative disorders, including autism, schizophrenia, Alzheimer’s disease, lateral amyotrophic sclerosis, etc. Impaired glutamate metabolism, along with an increase in the concentration of the glutamate free form in cytoplasm and extracellular space due to disturbing factors, is the main risk factor for CNS.