Elevated Maze Research Articles

Isolation, characterization and therapeutic potential of a novel furanoid diterpene lactone from Hedychium spicatum rhizomes: Insights into antioxidant, anxiolytic, and circadian rhythm modulating properties

BackgroundHedychium spicatum rhizomes is widely used in ayurvedic medicine and traditional medicine systems around the Himalayas. PurposeStandardization of Hedychium spicatum rhizome SCFE extract by Identification, Isolation, characterization, and screening of pharmacological activity of phytoconstituents. Study designSupercritical fluid extraction, column chromatography, spectroscopic analysis, in-silico, and in-vivo study of compound 1 (3-((E) -2-((1S,8aR)-3,5,5,8a-tetramethyl-4-oxo-1,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl) vinyl) furan-2(5H)-one). MethodsA supercritical fluid extract was prepared and further purified to obtain a novel Furanoid diterpene lactone compound 1 (3-((E) -2-((1S,8aR)-3,5,5,8a-tetramethyl-4-oxo-1,4,4a,5,6,7,8,8a-octahydro-naphthalen-1-yl) vinyl) furan-2(5H)-one). It was characterised using IR, LC-ESI/MS, 1H, 13C NMR, 2D NMR-COSY, NOESY, HMBC, and HSQC and thin-layer chromatography. Compound was tested for anxiolytic activity using various animal behavioural model included elevated maze plus test, light and dark box test, social interaction, actophotometer test, rotarod test. ResultsThe compound gives a false Dragendorff's test in favour of the presence of lactone. HPLC profiling was done using DAD using 30 % v/v of o-phosphoric acid (0.1 % v/v) in water and 70 % v/v of acetonitrile (ACN) in the mobile phase. Compound 1 having significant anxiolytic effect tested in animal behavioural model ****p < 0.0001 diazepam as standard. ConclusionFree radical scavenging activity suggested that compound 1 has good potential as an antioxidant, having IC50 values of 75.62 µg and 96.556 µg using DPPH and ABTS inhibition assays. ADMET prediction suggested that compound 1 follows Lipinski's rules of five, absorbed through the intestine, and penetrates the blood-brain barrier and CNS. In-silico studies, suggested that compound 1 has an affinity to bind with GABA, melatonin 1, and glutamate receptor 5 and In-vivo study suggest compound 1 will be a good candidate as anxiolytic agent. It can be used as a promising natural remedy for oxidative stress, mental health issues, and sleep-related disorders, warranting further exploration and clinical investigation.

Tomato juice regulates bile acid-TGR5 signaling and reverses cognitive deficit and neuroinflammation in high-fat high-cholesterol diet-induced mice

Cognitive deficits and neuroinflammation are significant complications associated with metabolic diseases induced by a high-fat, high-cholesterol (HFHC) diet. Although tomato juice (TJ) has shown potential benefits for brain health, its specific interventional role remains unclear. This research examined the capability of TJ to mitigate HFHC-induced cognitive deficits and delineated TJ's specific mechanisms against neuroinflammation. The results demonstrated that TJ effectively ameliorated cognitive impairments triggered by HFHC diets, improving spatial working memory, novel object recognition, and reducing anxiety-like behaviors in open space and elevated maze tests. Moreover, TJ mitigated neuronal damage, decreased the activity of immune cells, and diminished the level of COX-2 and iNOS in the hippocampus. Additionally, TJ decreased serum TNF-α and lipopolysaccharide levels, reduced liver inflammation, and improved intestinal barrier markers Claudin-1 and Mucin-2 expression. Fecal metabolomics demonstrated that TJ significantly upregulated bile acid metabolism-related pathways. TJ also altered the profile of serum bile acids, elevating the levels of Takeda G protein-coupled receptor 5 (TGR5)-activating bile acids, including deoxycholic acid, ursodeoxycholic acid, and tauroursodeoxycholic acid. TJ upregulated TGR5 protein expression and inhibited the phosphorylation of protein kinase B and nuclear factor kappa B proteins in the hippocampus. Notably, the positive effects of TJ on cognition and TGR5 activation were nullified in an antibiotic-treated mouse model, underscoring the essential role of the gut-brain axis in mediating TJ's neuroprotective effects. These findings propose that bile acid-TGR5 signaling may be associated with the anti-neuroinflammatory effects of TJ, which may represent a novel approach for neurogenic disease prevention.

Egg White Hydrolysate Mitigates Cadmium-induced Neurological Disorders and Oxidative Damage

We aimed to investigate whether the consumption of Egg White Hydrolysate (EWH) acts on nervous system disorders induced by exposure to Cadmium (Cd) in rats. Male Wistar rats were divided into (a) Control (Ct): H2O by gavage for 28 days + H2O (i.p. − 15th − 28th day); (b) Cadmium (Cd): H2O by gavage + CdCl2 − 1 mg/kg/day (i.p. − 15th − 28th day); (c) EWH 14d: EWH 1 g/kg/day by gavage for 14 days + H2O (i.p.- 15th − 28th day); (d) Cd + EWH cotreatment (Cd + EWHco): CdCl2 + EWH for 14 days; (e) EWH 28d: EWH for 28 days; (f) EWHpre + Cd: EWH (1st − 28th day) + CdCl2 (15th − 28th day). At the beginning and the end of treatment, neuromotor performance (Neurological Deficit Scale); motor function (Rota-Rod test); ability to move and explore (Open Field test); thermal sensitivity (Hot Plate test); and state of anxiety (Elevated Maze test) were tested. The antioxidant status in the cerebral cortex and the striatum were biochemically analyzed. Cd induces anxiety, and neuromotor, and thermal sensitivity deficits. EWH consumption prevented anxiety, neuromotor deficits, and alterations in thermal sensitivity, avoiding neuromotor deficits both when the administration was performed before or during Cd exposure. Both modes of administration reduced the levels of reactive species, and the lipid peroxidation increased by Cd and improved the striatum’s antioxidant capacity. Pretreatment proved to be beneficial in preventing the reduction of SOD activity in the cortex. EWH could be used as a functional food with antioxidant properties capable of preventing neurological damage induced by Cd.

Long-term consumption of natural sweeteners differentially modulates stress, anxiety, and depression behaviors in C57BL/6 female mice

Excessive consumption of added sugars has been associated with psychiatric disorders such as stress, anxiety, and depression, especially in women. The aim of this study was to evaluate the effect of natural sweeteners on stress, anxiety, and depression behaviors and physiological effects in C57BL/6 female mice (n = 72). Agave syrup (AS), monk fruit (MF), glycyrrhizin (GLY), xylitol (XYL), and allulose (AL) were administered in the drinking water for 20 weeks. The intake of food and drink, and body weight of the mice was evaluated weekly. Moreover, forced swimming, tail suspension, elevated maze tests, morphometric analyses, organ weight/body weight index estimation, leukocyte count and granulocytes/leukocytes (G/L), and plasma glucose levels were performed at the end of the experimental trial. According to the results, all sweeteners increased weight gain (p < 0.01) but not food and drink intakes or glucose levels. The consumption of AS, MF, XYL, and AL decreased the symptoms of depression, while the consumption of AS, GLY, XYL, and AL increased the signs of anxiety (p < 0.001). In leukocyte count, all sweeteners caused changes compared to the control group (CON) (p < 0.0001). Organ weights, lengths, and G/L ratio showed significant reductions for all sweeteners except GLY. In conclusion, the consumption of natural sweeteners in female mice triggers alterations in behavioral disorders and other physiological responses.

0065 A Novel Automated Task for Spatial Learning in Rodents

Abstract Introduction Spatial learning in rodents is useful for addressing a variety of research questions. We set out to create a fully automated spatial learning task that required rodents to make a sequence of cued navigational decisions. We used this maze to investigate the impact of sleep on insight gain, a sudden rather than gradual acquisition of a skill or behavior. Methods We designed a circular four-quadrant elevated maze. Each quadrant had three choice points on a branched arm, consisting of a reward well and cue light. To discourage rats from backtracking, motorized doors were placed between quadrants. Rats were trained to follow the light for a water reward. Their position was tracked by custom MATLAB code processing live video from a ceiling-mounted camera; the code also controlled all components of the maze, calculated and presented novel routes through the maze, analyzed results in real time, and maintained records of each rat across sessions. After an average of five days rats reached criterion in pretraining (following lights in pseudorandom positions) and were taught a hidden rule: the direction cued on the second quadrant was the correct direction on the fourth (uncued) quadrant. Rats completed one session each in the morning and afternoon, separated by 3h of sleep opportunity or sleep disruption, achieved by gentle handling. This was repeated after a night of sleep opportunity or sleep disruption for a total of four sessions. Results Rats quickly learned and consistently chose the correct well, remaining motivated for 96 consecutive trials. Rats were said to have gained insight if they demonstrated significant learning of the hidden rule. Although no animals have yet met this criterion, there was a trend of sleep-disrupted rats performing worse, suggesting that sleep plays an important role in consolidating the spatial rules of the task. Conclusion The versatility of this maze can accommodate many tasks not limited to insight gain specifically. Delivering rewards consistently at multiple distinct locations is a valuable technique for investigating spatial learning, navigation, and decision making, making this maze a powerful tool for investigating interventions for disease models that implicate the hippocampus or striatum. Support (if any)

Effect of Ganmai Dazao Decoction on ethology of rats with PTSD and its mechanism

This study aimed to explore the effect of Ganmai Dazao Decoction on the ethology of rats with posttraumatic stress disorder(PTSD) and study the related mechanism through the changes in magnetic resonance imaging and protein expression. Sixty rats were randomly divided into 6 groups, namely the normal group, the model group, the low(1 g·kg~(-1)), medium(2 g·kg~(-1)), and high-dose Ganmai Dazao Decoction groups(4 g·kg~(-1)), and the positive control group(intragastric administration with 10.8 mg·kg~(-1) of fluoxetine), with 10 rats in each group. Two weeks after inducing PTSD by single-prolonged stress(SPS) in rats, the positive control group was given fluoxetine hydrochloride capsule by gavage, the low, medium, and high-dose groups were given Ganmai Dazao Decoction by gavage, and both the normal group and the model group were given the same volume of normal saline by gavage, each for 7 days. The open field experiment, elevated cross elevated maze, forced swimming experiment, and new object recognition test were carried out for the behavioral test. Three rats in each group were selected to detect the expression of neuropeptide receptor Y1(NPY1R) protein in the hippocampus by Western blot. Then, the other three rats in each group were selected to use the 9.4T magnetic resonance imaging experiment to observe the overall structural changes in the brain region and the anisotropy fraction of the hippocampus. The results of the open field experiment showed that the total distance and central distance of rats in the model group were significantly lower than those in the normal group, and the total distance and central distance of rats in the middle and high-dose Ganmai Dazao Decoction groups were higher than those in the model group. The results of the elevated cross maze test showed that medium and high-dose Ganmai Dazao Decoction remarkably increased the number of open arm entries and the residence time of open arm of rats with PTSD. The results of the forced swimming experiment showed that the immobility time in the water of the model group rats was significantly higher than that of the normal group, and Ganmai Dazao Decoction hugely reduced the immobility time in the water of rats with PTSD. The results of the new object recognition test showed that Ganmai Dazao Decoction significantly increased the exploration time of new objects and familiar objects in rats with PTSD. The results of Western blot showed that Ganmai Dazao Decoction significantly reduced the expression of NYP1R protein in the hippocampus of rats with PTSD. The 9.4T magnetic resonance examination found that there was no significant difference in the structural image among the groups. In the functional image, the fractional anisotropy(FA value) of the hippocampus in the model group was significantly lower than that in the normal group. The FA value of the hippocampus in the middle and high-dose Ganmai Dazao Decoction groups was higher than that in the model group. Ganmai Dazao Decoction reduces the injury of hippocampal neurons by inhibiting the expression of NYP1R in the hippocampus of rats with PTSD, thereby improving the nerve function injury of rats with PTSD and playing a neuroprotective role.

Melatonin alleviates PTSD-like behaviors and restores serum GABA and cortisol levels in mice.

Melatonin is an endogenous hormone which modulates sleep-wake cycles. Previous studies have found a close correlation between melatonin and post-traumatic stress disorder (PTSD), a trauma- and stress-related psychiatric disorder with symptoms of sleep disturbance. However, it is still unclear if melatonin can have a therapeutic effect on PTSD. This study aimed to investigate the effects of melatonin on foot shocks induced PTSD-like behaviors and abnormal neuroendocrine levels in mice. As compared to no-shock controls, PTSD-like mice spent significantly more time freezing and displayed less rearing in a contextual fear test, spent significantly less time in and had fewer entries into open arms in an elevated maze test, and spent significantly less time in and had fewer entries into a light box in a light-dark transition task. In addition, serum GABA and cortisol levels were both found to be significantly decreased, whereas epinephrine levels were significantly increased in the PTSD-like mice. Our results showed that intraperitoneal injections of melatonin (2 mM, but not 0.2 nor 20 mM, 0.1 ml/day for two consecutive weeks) alleviated PTSD-like behaviors and restored serum GABA and cortisol levels. Further, it was found that melatonin receptor 1/2 antagonist luzindole significantly blocked the beneficial effects of melatonin for PTSD-like behaviors and serum GABA and cortisol levels, whereas melatonin receptor 2 antagonist 4-P-PDOT slightly blocked these effects. These results indicate that melatonin has a potential therapeutic effect on PTSD-like symptoms in mice, and melatonin receptor 1 mediated the effect.

VTA-NAc glutaminergic projection involves in the regulation of pain and pain-related anxiety.

Besides the established role of dopamine neurons and projections in nociceptive stimuli, the involvement of ventral tegmental area (VTA) glutamatergic projections to nucleus accumbens (NAc) in pain remains unknown. In the present study, we aimed to examine the role of VTA glutamatergic projections to NAc in painful stimuli and its related behavioral changes. Unilateral chronic constrictive injury (CCI) of sciatic nerve or intraplantar hind paw injections (i.pl.) of complete Freund's adjuvant (CFA) were used to develop pathological pain models in wild-type and VGluT2-Cre mice. The involvement of VTA glutamatergic neurons with projections to NAc in CCI-induced pain model was noted by c-Fos labeling and firing rate recordings. Pain response and pain-related behavior changes to the artificial manipulation of the VTA glutamatergic projections to NAc were observed by Hargreaves tests, von Frey tests, open field tests, elevated maze tests, and sucrose preference tests. Glutamatergic neurons in VTA had efferent inputs to shell area of the NAc. The CCI pain model significantly increased neuronal activity and firing rate in VTA glutamate neurons with projections to NAc. The photoinhibition of these glutamatergic projections relieved CCI-induced neuropathic pain and CFA-induced acute and chronic inflammatory pain. Moreover, pathological neuropathic pain-induced anxiety and less sucrose preference were also relieved by inhibiting the VTA glutamatergic projections to NAc. Together, glutamatergic inputs from VTA to NAc contribute to chronic neuropathic and inflammatory pain and pain-related anxiety and depressive behaviors, providing a mechanism for developing novel therapeutic methods.

Methamphetamine Induces Systemic Inflammation and Anxiety: The Role of the Gut-Immune-Brain Axis.

Methamphetamine (METH) is a highly addictive drug abused by millions of users worldwide, thus becoming a global health concern with limited management options. The inefficiency of existing treatment methods has driven research into understanding the mechanisms underlying METH-induced disorders and finding effective treatments. This study aims to understand the complex interactions of the gastrointestinal–immune–nervous systems following an acute METH dose administration as one of the potential underlying molecular mechanisms concentrating on the impact of METH abuse on gut permeability. Findings showed a decreased expression of tight junction proteins ZO-1 and EpCAm in intestinal tissue and the presence of FABP-1 in sera of METH treated mice suggests intestinal wall disruption. The increased presence of CD45+ immune cells in the intestinal wall further confirms gut wall inflammation/disruption. In the brain, the expression of inflammatory markers Ccl2, Cxcl1, IL-1β, TMEM119, and the presence of albumin were higher in METH mice compared to shams, suggesting METH-induced blood–brain barrier disruption. In the spleen, cellular and gene changes are also noted. In addition, mice treated with an acute dose of METH showed anxious behavior in dark and light, open field, and elevated maze tests compared to sham controls. The findings on METH-induced inflammation and anxiety may provide opportunities to develop effective treatments for METH addiction in the future.

FTH1- and SAT1-Induced Astrocytic Ferroptosis Is Involved in Alzheimer's Disease: Evidence from Single-Cell Transcriptomic Analysis.

Objectives: Despite significant advances in neuroscience, the mechanisms of AD are not fully understood. Single-cell RNA sequencing (scRNA-seq) techniques provide potential solutions to analyze cellular composition of complex brain tissue and explore cellular and molecular biological mechanisms of AD. Methods: We investigated cellular heterogeneity in AD via utilization of bioinformatic analysis of scRNA-seq in AD patients and healthy controls from the Gene Expression Omnibus (GEO) database. The “GOplot” package was applied to explore possible biological processes in oligodendrocytes, astrocytes, and oligodendrocyte progenitor cells (OPCs). Expression patterns and biological functions of differentially expressed genes (DEGs) from scRNA-seq data were validated in RNA sequencing data. DEGs in astrocytes interacted with ferroptosis-related genes in FerrDb. CCK-8 and EdU assays were performed to measure cell proliferation ability. ROS, Fe2+ level, mitochondrial membrane potentials, iron concentrations, and total iron binding capacity (TIBC) in serum were evaluated. Y-maze and elevated maze were used to measure anxiety-like behavior. Autonomous and exploration behaviors or learning and memory ability in mice were analyzed using open field test and novel object recognition test. Results: Multiple clusters were identified, including oligodendrocytes, astrocytes, OPCs, neurons, microglia, doublets, and endothelial cells. Astrocytes were significantly decreased in AD, while oligodendrocytes and OPCs increased. Cell-to-cell ligand–receptor interaction analysis revealed that astrocytes, neurons, and OPCs mainly established contacts with other cells via the NRG3–ERBB4 ligand–receptor pair. GO and KEGG analyses found that astrocytes were enriched in the ferroptosis pathway. FTH1 and SAT1 in astrocytes were identified as hub mRNAs associated with ferroptosis. Serum iron concentration of 5xFAD mice was higher than that of WT, and emotional and cognitive function were significantly impaired as compared to WT. Serum iron concentration was negatively correlated with number of astrocytes and percentage of time spent entering the novelty arm in the Y-maze test, while it was positively correlated with percentage of time spent in the central area. Meanwhile, number of astrocytes was negatively correlated with percentage of time spent in the central area, while it was positively correlated with percentage of time spent entering the novelty arm. Conclusions: Through scRNA-seq analysis, we found that ferroptosis was activated in astrocytes and may contribute to the pathophysiological process in the entorhinal cortex. FTH1 and SAT1 were identified to impact astrocyte ferroptosis. Emotional and cognitive impairment in AD was associated with astrocyte ferroptosis. Our findings provide clues to reveal the pathophysiological processes following AD at the cellular level and highlight potential drug targets for the treatment of AD.

Measures of cardiovascular function suggest autonomic nervous system dysregulation after surgical induction of joint injury in the male Lewis rat

Functional changes in the autonomic nervous system may help explain variability in the progression of knee osteoarthritis (OA). Thus, the objective of this study was to evaluate autonomic nervous system shifts, measured via heart rate response variables, in rat knee joint injury and OA models. Cardiovascular characteristics were measured at baseline and bi-weekly for 8 weeks after skin incision, medial collateral ligament transection (MCLT), or MCLT+medial meniscus transection (MCLT+MMT). Heart rate was also assessed during a mild stressor (elevated maze). At endpoint, cardiovascular responses to mechanical knee stimuli were evaluated, as well as responses to 1-phenylbiguanide, a 5HT3A receptor agonist with reported ability to stimulate vagal responses. During low activity, a slower heart rate occurred in MCLT (299±10 bpm) and MCLT+MMT (310±10 bpm) animals compared to controls (325±10 bpm). Furthermore, patellar ligament mechanical stimuli produced an immediate decrease in heart rate and blood pressure in all groups. Finally, a larger drop in heart rate was observed in MCLT (252±40 bpm) and MCLT+MMT (263±49 bpm) following administration of 1-phenylbiguanide compared to skin incision (168±45 bpm). Acute mechanical stimulation of the patellar ligament produced drops in heart rate, suggesting a possible joint-brain connection that modulates autonomic responses. With both joint injury, cardiac vagal activation was altered in response to pharmacological stimulation, with chronic longitudinal heart rate reduction. These data provide some preliminary evidence of potential functional shifts in autonomic nervous system function in models of joint injury and OA.

Effects of parasitism on antipredatory responses and defensive behaviors in the subterranean rodent Ctenomys talarum

Predation represents an important evolutionary force shaping specific adaptations. Prey organisms present behavioral adaptations that allow them to recognize, avoid, and defend themselves from their predators. In addition to predation, there is a growing consensus about the role of parasitism in the structuring of biological communities. In vertebrates, the effects on hosts include changes in daily activity, feeding, mate selection, reproduction, and modifications in responses to environmental stimuli. These behavioral variations can benefit the parasite (parasitic manipulation), benefit the host, or appear as a side effect of the infection. We evaluated the influence of parasitism on the behavioral and physiological responses of the tuco-tucos of the Talas (Ctenomys talarum Thomas, 1898) to predator cues. We found that individuals exposed to cat odors and immobilization entered less often and spent less time in the transparent arms of elevated maze, exhibiting a preference for protected areas (anxiogenic response). Additionally, we evaluated if the presence of parasites affected antipredatory behaviors in C. talarum (naturally parasitized, deparasitized, or inoculated with Eimeria sp.). We did not find differences among the groups with regards to responses to predator cues. Therefore, while exposure to predator cues triggered a stress response, the manipulation of parasite loads did not modify homeostasis under these experimental conditions.

Undesired Effects of Bioinsecticides Molecules in Wistar Rats: Case of Spirotetramat, Citrulus Colocynthis and Cleome Arabica Extracts

The use of pesticides is becoming an indispensable technique in most agricultural practices, regardless of the level of development of the country. Currently, the pesticides used are often less toxic and more specific and are based on insect physiology. Recent studies indicate that pesticide intoxication induces oxidative stress. This work aims to study the neurobehavioral consequences of the administration of two insecticides currently widely used in agriculture: spirotetramat (an inhibitor of lipid synthesis in insects) and the ethanolic extract of Citrullus colocynthis (a plant endemic to the Algerian Sahara) and the ethanolic extract of Cleome arabica (Capparidaceae) The different behavioral tests (elevated cross maze, open fields and forced swimming) show that the have a significant impact on the degree of anxiety of rodents.These products significantly influence the biochemical parameters (blood sugar, cholesterol, triglycerides, urea, creatinine), the hormone Adreno CorticoTropic Hormone, acetylcholine esterase,

Effects of treadmill exercise on anxiety-like behavior in association with changes in estrogen receptors ERα, ERβ and oxytocin of C57BL/6J female mice.

Exercise can reduce the incidence of stress-related mental diseases, such as depression and anxiety. Control group was neither exposed to CVMS nor TRE (noCVMS/noTRE). Females were tested and levels of serum17-beta-oestradiol (E2), estrogen receptors α immunoreactive neurons (ERα-IRs), estrogen receptors β immunoreactive neurons (ERβ-IRs) and oxytocin immunoreactive neurons (OT-IRs) were measured. The results showed there’s increased anxiety-like behaviors for mice from CVMS/noTRE, CVMS/higher speed TRE (CVMS/HTRE) and noCVMS/HTRE groups when they were put in open field and elevated maze tests. They had lower serum E2 levels than mice from CVMS/low-moderate speed TRE (CVMS/LMTRE), noCVMS/LMTRE and noCVMS/noTRE groups. The three groups of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice had more ERα-IRs and less ERβ-IRs in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA), hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The number of OT-IRs in PVN and SON of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice was also lower than that of mice from CVMS/LMTRE, noCVMS/LMTRE and noCVMS/noTRE groups. Interestingly, CVMS/LMTRE and noCVMS/LMTRE mice were similar to noCVMS/noTRE mice in that they did not show anxiety, while CVMS/HTRE and noCVMS/HTRE mice did not, which were similar to the mice in CVMS/noTRE. We propose that LMTRE instead of HTRE changes the serum concentration of E2. ERβ/ERα ratio and OT level in the brain may be responsible for the decrease in anxiety-like behavior in female mice exposed to anxiety-inducing stress conditions.

Ameliorative Potential of Glycyrrhiza glabra Extracts on Memory Impairments in Stress Triggered Rats

Background: Glycyrrhiza glabra Linn. (Family: Fabaceae) is known to be a very useful medicinal plant in the Traditional Medicinal Systems since centuries. With ethnopharmacological values, it is a well-reported plant for its anti-inflammatory, antioxidant, anxiolytic, expectorant and antidepressant activities. Objective: Although the plant has been described to possess memory enhancing activity, the present study focused on examining the comparative effect of Glycyrrhiza glabra extracts viz. flavonoid rich (GGFE) and glycyrrhizin rich (GGGE) in stress-triggered rats and providing future research insights on this herbal drug, for which no scientific justification has been reported till now. Methods: Male Wister rats divided into 7 different groups (n= 6 per group) were given chronic foot-shock stress for 21 successive days with scheduled administration of the extracts (50 and 100 mg/kg) and standard drug (10 mg/kg) for 28 days. Elevated Plus Maze, Rectangular Maze, Morris Water Maze, and Locomotor activity were performed to test behavioral alteration and learning ability of stressed rats. Further, rats were sacrificed to assay acetylcholinesterase activity and antioxidant activity in brain samples for their mechanistic role in learning and memory. Results: Extracts of Glycyrrhiza glabra indicated a significant alteration in stress-induced learning and memory deficiency in behavioral parameters studied. These extracts also modulated significant changes in acetylcholinesterase and antioxidant enzyme activity to improve the learning and memory of stressed rats. Conclusions: Both the extracts of Glycyrrhiza glabra (GGFE and GGGE) were found to exert memory enhancing property in stress-triggered rats. Moreover, the comparative results confirmed that the high potential of GGGE in comparison to GGFE might be due to the rich glycyrrhizin content present in GGGE responsible for acetylcholinesterase and antioxidant enzyme modulatory activities. Therefore, GGGE could be used as a promising lead for further mechanistic and molecular studies for defining the role of glycyrrhizin in Glycyrrhiza glabra.

Evaluation of the effect of high air temperature on the behavioural activity and physical performance of animals (in a rat model)

Introduction. The profession of firefighters belongs to extreme activities. Fire hazards include flames, sparks, heat flow, elevated ambient temperatures, increased concentrations of toxic combustion and thermal decomposition products, decreased oxygen concentrations, and reduced visibility in smoke. High air temperature during fire extinguishing is one of the main adverse physical factors affecting firefighters’ bodies. Material and methods. The study was carried out on 124 outbred white male 3-month rats weighing 250-300 g, divided randomly into two groups: the first group (62 rats) underwent single hyperthermia. The second group (62 rats) experienced daily hyperthermia for 14 days. The study of the behavioural activity of animals was carried out after single and prolonged hyperthermia using the following methods: “Open field”, “Elevated cruciform maze”, Porsolt’s test, running on a treadmill. The tests were performed two times: the first time - before exposure, the second - after, with intervals between tests of at least two weeks. Results. The data obtained indicate that the high ambient temperature causes changes in the behavioural responses in animals, which is expressed by an increase in the level of anxiety, a decrease in motor and research activity, the development of depressive states, and a decrease in physical endurance. Conclusion. An experimental model of extreme heat exposure on animals showed the emergence and persistence of changes in animals’ behavioural activity and physical performance indicators. This experiment can be used to study the long-term effects of high temperatures on firefighters’ bodies.

Melatonin pretreatment alleviates blast-induced oxidative stress in the hypothalamic-pituitary-gonadal axis by activating the Nrf2/HO-1 signaling pathway

Although melatonin has been demonstrated to exert a potent antioxidant effect, the ability of melatonin to alleviate blast-induced oxidative stress in the hypothalamic-pituitary-gonadal (HPG) axis remains unclear. This study aimed to elucidate the effects and underlying mechanism of melatonin pretreatment on the HPG axis disrupted by blast injury. Sixty C57BL/6 mice were randomly divided into control, blast, and blast + melatonin groups for behavioral experiments. The elevated maze experiment, open field experiment, and Morris Water Maze experiment were carried out on the 7th, 14th and 28th day after the blast injury. Fifty Sprague Dawley rats were randomly divided into control, blast, blast + melatonin, and blast + melatonin + luzindole groups for hormone assays and molecular and pathological experiments. Blood samples were used for HPG axis hormone detection and ELISA assays, and tissue samples were used to detect oxidative stress, inflammation, apoptosis, and stress-related protein levels. The results showed that melatonin pretreatment alleviated blast-induced behavioral abnormalities in mice and maintained the HPG axis hormone homeostasis in rats. Additionally, melatonin significantly reduced MDA5 expression and increased the expression of Nrf2/HO-1. Moreover, melatonin significantly inhibited NF-κB expression and upregulated IL-10 expression, and it reversed the blast-induced high expression of caspase-3 and Bax and the low expression of Bcl-2. Furthermore, luzindole counteracted melatonin inhibition of NF-κB and upregulated Nrf2/HO-1. Melatonin significantly alleviated blast-induced HPG axis hormone dyshomeostasis, behavioral abnormalities, oxidative stress, inflammation, and apoptosis, which may be achieved by upregulating the Nrf2/HO-1 signaling pathway. Our study suggested that melatonin pretreatment is a potential treatment for blast-induced HPG axis hormonal and behavioral abnormalities.

Antistress action of Fornicium uniflorum extract in chronic stress

The anti-stress effect of the Fornicium uniflorum extract was studied in Wistar rats in model of chronic unpredictable stress. Stress disorders in rats were determined using methods open field, plus elevated maze, forced swimming test, tail suspension model, sucrose test, as well as changes in the weight indicators of stress target organs. The course administration of F. uniflorum extract to rats under conditions of chronic stress prevented the development of behavioral disorders: the indicators of horizontal, vertical motor activities and mink reflex in the open field were, respectively, 1.5, 4 and 2.5 times higher than those of control rats (without treatment) (p 0.05); the time spent in the open arms of the plus elevated maze and the number of entries into them were respectively 3 and 8.5 times greater than the indices of control rats (p 0.05); the time of immobility of rats in the forced swimming test and the model of hanging by the tail were 2 and 3 times less than in the control; the volume of consumption of sucrose solution in the sucrose test by rats was 1.4 times higher than that of control rats (p 0.05), which indicated the antidepressant activity. In the rats treated with F. uniflorum, no changes in the relative mass of stress target organs were noted, in contrast to the control (p 0.05). Therefore, the course administration of F. uniflorum has an anti-stress and antidepressant effect in chronic unpredictable stress.

Transcriptome Changes in Three Brain Regions during Chronic Lithium Administration in the Rat Models of Mania and Depression.

Lithium has been the most important mood stabilizer used for the treatment of bipolar disorder and prophylaxis of manic and depressive episodes. Despite long use in clinical practice, the exact molecular mechanisms of lithium are still not well identified. Previous experimental studies produced inconsistent results due to different duration of lithium treatment and using animals without manic-like or depressive-like symptoms. Therefore, we aimed to analyze the gene expression profile in three brain regions (amygdala, frontal cortex and hippocampus) in the rat model of mania and depression during chronic lithium administration (2 and 4 weeks). Behavioral changes were verified by the forced swim test, open field test and elevated maze test. After the experiment, nucleic acid was extracted from the frontal cortex, hippocampus and amygdala. Gene expression profile was done using SurePrint G3 Rat Gene Expression whole transcriptome microarrays. Data were analyzed using Gene Spring 14.9 software. We found that chronic lithium treatment significantly influenced gene expression profile in both mania and depression models. In manic rats, chronic lithium treatment significantly influenced the expression of the genes enriched in olfactory and taste transduction pathway and long non-coding RNAs in all three brain regions. We report here for the first time that genes regulating olfactory and taste receptor pathways and long non-coding RNAs may be targeted by chronic lithium treatment in the animal model of mania.

Implementation of Basic Computer Vision Methods for Analyzing the Results of Biological Experiments

The article discusses the video processing methods necessary for the automation of processing the results of the experiments “Morris Water Maze”, “Open Field”, “Elevated Cross-shaped Maze”, which are used to study the behavior of laboratory mice depending on various external factors, as well as an experiment with daily tracking Rhesus macaque activity. To process the received information, the C++ programming language is used including the OpenCV 3.2 and Qt 5.2 libraries. Later in the paper new applications are discussed to further the research based on findings described here. For further use monkey observation is proposed. The choice was made based on similarity between discussed and proposed methods for video processing and automation of experiments. For reviewed methods their advantages and disadvantages are included in the work. For each of experiments “Morris Water Maze”, “Open Field”, “Elevated Crossshaped Maze” there is corresponding image sequence for anyone unfamiliar with the topic.