Arm Maze Research Articles

Microglia ameliorate delirium-like phenotypes in a murine model of acute ventilator-induced lung injury

BackgroundDelirium affects 50–85% of patients on mechanical ventilation and is associated with increased mortality, prolonged hospitalization, and a three-fold higher risk of dementia. Microglia, the resident immune cells of the brain, exhibit both neuroprotective and neurotoxic functions; however, their effects in mechanical ventilation-induced acute lung injury (VILI) are unknown. We hypothesize that in a model of short-term VILI, microglia play a neuroprotective role to ameliorate delirium-like phenotypes.MethodsMicroglia depletion (n = 18) was accomplished using an orally administered colony stimulating factor 1 receptor inhibitor, while controls received a vehicle diet (n = 18). We then compared extent of neuronal injury in the frontal cortex and hippocampus using cleaved caspase-3 (CC3) and multiple delirium-like behaviors in microglia depleted and non-microglia depleted male mice (C57BL/6 J aged 4–9 months) following VILI. Delirium-like behaviors were evaluated using the Open Field, Elevated Plus Maze, and Y-maze assays. We subsequently evaluated whether repopulation of microglia (n = 14 repopulation, 14 vehicle) restored the phenotypes.ResultsFrontal/hippocampal neuronal CC3 levels were significantly higher in microglia depleted VILI mice compared to vehicle-treated VILI controls (p < 0.01, p < 0.01, respectively). These structural changes were accompanied by worse delirium-like behaviors in microglia depleted VILI mice compared to vehicle controls. Specifically, microglia depleted VILI mice demonstrated: (1) significantly increased time in the periphery of the Open Field (p = 0.01), (2) significantly increased coefficient of variation (p = 0.02), (3) trend towards reduced time in the open arms of the Elevated Plus Maze (p = 0.09), and (4) significantly decreased spontaneous alternations on Y-maze (p < 0.01). There was a significant inverse correlation between frontal CC3 and percent spontaneous alternations (R2 = 0.51, p < 0.01). Microglia repopulation showed a near-complete return to vehicle levels of delirium like-behaviors.ConclusionsThis study demonstrates that microglia depletion exacerbates structural and functional delirium-like phenotypes after VILI, while subsequent repopulation of microglia restores these phenotypes. These findings suggest a neuroprotective role for microglia in ameliorating neuronal and functional delirium-like phenotypes and call for consideration of interventions that leverage endogenous microglia physiology to mitigate delirium.

An Alternative Analysis of Computational Learning within Behavioral Neuropharmacology in an Experimental Anxiety Model Investigation

Behavioral neuropharmacology, a branch of neuroscience, uses behavioral analysis to demonstrate treatment effects on animal models, which is fundamental for pre-clinical evaluation. Typically, this determination is univariate, neglecting the relevant associations for understanding treatment effects in animals and humans. This study implements regression trees and Bayesian networks from a multivariate perspective by using variables obtained from behavioral tests to predict the time spent in the open arms of the elevated arm maze, a key variable to assess anxiety. Three doses of allopregnanolone were analyzed and compared to a vehicle group and a diazepam-positive control. Regression trees identified cut-off points between the anxiolytic and anxiogenic effects, with the anxiety index standing out as a robust predictor, combined with the percentage of open-arm entries and the number of entries. Bayesian networks facilitated the visualization and understanding of the interactions between multiple behavioral and biological variables, demonstrating that treatment with allopregnanolone (2 mg) emulates the effects of diazepam, validating the multivariate approach. The results highlight the relevance of integrating advanced methods, such as Bayesian networks, into preclinical research to enrich the interpretation of complex behavioral data in animal models, which can hardly be observed with univariate statistics.

The effect of 2,6-dimethylpyridine N-oxide on cognitive functions and emotional state of rats following ins long-term oral administration

Background. Global anthropogenic environmental pollution, intensification of production, daily physical, emotional and psychogenic stress on humans, as well as the working environment provoke a variety of diseases, fatigue, and cognitive impairment, etc. This may be attributed to a reduced nonspecific resistance of the health system and the development of stressful conditions. Therefore, one of the focal points of preventive toxicology is the development of agents with adaptogenic properties that would prevent the occurrence of harmful effects under the influence of stressors. The aim of the present study was to examine the effect of 2,6-dimethylpyridine N-oxide on cognitive functions and emotional status of rats following its long-term oral administration. Materials and Methods. The plant growth regulator (PGR) Ivin (2,6-dimethylpyridine N-oxide, 99.9%) was chosen for the study. Adaptogen Eleutherococcus was used as a reference agent. The study was conducted on Wistar Hannover rats divided into 2 cohorts. Each cohort included the following groups: 1 – intact animals, 2 – control (distilled water), 3 and 4 – Ivin at doses of 13.0 and 0.013 mg/kg (1/100 and 1/100000 LD50), respectively, 5 – Eleutherococcus at a dose of 50 mg/kg. Exposure period – 28 days, oral route of administration. The state of the central nervous system was assessed by behavioural reactions in the Morris Water Maze and the Elevated Plus Maze. Results. Ivin at doses of 13 and 0.013 mg/kg increased the ability to learn and to form short- and long-term memory in rats, as evidenced by a decrease in the average time of platform location in the Morris Water Maze test. Ivin at a dose of 0.013 mg/kg significantly increased the number of rearings in closed arms of the Elevated Plus Maze, indicating its anxiolytic effect. The anti-anxiety effect of Ivin needs to be confirmed by additional studies in the Open Field and/or Hole-board tests. The effectiveness of Ivin in terms of the studied parameters was similar or exceeded those of the known adaptogen Eleutherococcus.

Time cells in the retrosplenial cortex.

The retrosplenial cortex (RSC) is a key component of the brain's memory systems, with anatomical connections to the hippocampus, anterior thalamus, and entorhinal cortex. This circuit has been implicated in episodic memory and many of these structures have been shown to encode temporal information, which is critical for episodic memory. For example, hippocampal time cells reliably fire during specific segments of time during a delay period. Although RSC lesions are known to disrupt temporal memory, time cells have not been observed there. In this study, we reanalyzed archival RSC neuronal firing data during the intertrial delay period from two previous experiments involving different behavioral tasks, a blocked alternation task and a cued T-maze task. For the blocked alternation task, rats were required to approach the east or west arm of a plus maze for reward during different blocks of trials. Because the reward locations were not cued, the rat had to remember the goal location for each trial. In the cued T-maze task, the reward location was explicitly cued with a light and the rats simply had to approach the light for reward, so there was no requirement to hold a memory during the intertrial delay. Time cells were prevalent in the blocked alternation task, and most time cells clearly differentiated the east and west trials. We also found that RSC neurons could exhibit off-response time fields, periods of reliably inhibited firing. Time cells were also observed in the cued T-maze, but they were less prevalent and they did not differentiate left and right trials as well as in the blocked alternation task, suggesting that RSC time cells are sensitive to the memory demands of the task. These results suggest that temporal coding is a prominent feature of RSC firing patterns, consistent with an RSC role in episodic memory.

The Projection-Specific Noradrenergic Modulation of Perseverative Spatial Behavior in Adult Male Rats.

Adaptive behavior relies on efficient cognitive control. The anterior cingulate cortex (ACC) is a key node within the executive prefrontal network. The reciprocal connectivity between the locus ceruleus (LC) and ACC is thought to support behavioral reorganization triggered by the detection of an unexpected change. We transduced LC neurons with either excitatory or inhibitory chemogenetic receptors in adult male rats and trained rats on a spatial task. Subsequently, we altered LC activity and confronted rats with an unexpected change of reward locations. In a new spatial context, rats with decreased noradrenaline (NA) in the ACC entered unbaited maze arms more persistently which was indicative of perseveration. In contrast, the suppression of the global NA transmission reduced perseveration. Neither chemogenetic manipulation nor inactivation of the ACC by muscimol affected the rate of learning, possibly due to partial virus transduction of the LC neurons and/or the compensatory engagement of other prefrontal regions. Importantly, we observed behavioral deficits in rats with LC damage caused by virus injection. The latter finding highlights the importance of careful histological assessment of virus-transduced brain tissue as inadvertent damage of the targeted cell population due to virus neurotoxicity or other factors might cause unwanted side effects. Although the specific role of ACC in the flexibility of spatial behavior has not been convincingly demonstrated, our results support the beneficial role of noradrenergic transmission for an optimal function of the ACC. Overall, our findings suggest the LC exerts the projection-specific modulation of neural circuits mediating the flexibility of spatial behavior.

Safeguarding Neuronal Integrity: Unveiling Possible Role of NFκB in the Neuroprotective Efficacy of Andrographolide Contrary to Aluminium Chloride-induced Neurotoxicity and Associated Spatial Memory Impairments in Rats.

The current study was structured to evaluate the neuroprotective properties of andrographolide in the context of aluminum chloride (AlCl3)-induced neurotoxicity, along with its concurrent impact on spatial memory impairment in Wistar rats. The present investigation elucidated the biochemical and neurobehavioral outcomes of andrographolide treatment in rats, emphasizing the areas of the brain associated with memory, i.e., the cortex and the hippocampus. Prolonged dosing of AlCl3 (7 mg/kg) intraperitoneally for 10 days exhibited a substantial enhancement in the values of oxidative stress markers associated with a reduction in the concentrations of antioxidant enzymes within the brain. The selection of andrographolide doses (1, 2, and 3 mg/kg) was grounded in precedent safety and toxicity investigations, with subsequent oral administration. The evaluation of behavioral parameters, specifically spatial memory, was conducted through the utilization of the Radial Eight Arm Maze (RAM) test. On the concluding day of the experiment, the assessment encompassed biochemical parameter analysis and histological scrutiny of the brain tissue. The oral dosing of andrographolide at 1, 2, and 3 mg/kg, in conjunction with AlCl3, effectively mitigated the behavioral deficits induced by aluminum exposure. Notably, a significant suppression of NFκB was uncovered in the rats treated with andrographolide. Furthermore, histopathological examinations of the cortex and hippocampus of rat brains provided corroborative evidence, demonstrating that andrographolide substantially alleviated the toxic impact of AlCl3, thereby maintaining the typical histoarchitectural arrangement of these regions. These findings collectively suggest that andrographolide holds the potential to counteract memory impairment instigated by aluminum toxicity, accomplished through the modulation of NFκB activity and the amelioration of the adverse consequences of AlCl3 exposure.

Development of a New Scoring System in Higher Animals for Testing Cognitive Function in the Newborn Period: Effect of Prenatal Hypoxia-Ischemia

Introduction: Enhanced models for assessing cognitive function in the neonatal period are imperative in higher animals. Postnatal motor deficits, characteristic of cerebral palsy, emerge in newborn kits within our prenatal rabbit model of hypoxia-ischemia (HI). In humans, prenatal HI leads to intellectual disability and cerebral palsy. In a study examining cognitive function in newborn rabbits, we explored several questions. Is there a distinction between conditioned and unconditioned kits? Can the kits discern the human face or the laboratory coat? Do motorically normal kits, born after prenatal HI, exhibit cognitive deficits? Methods: The conditioning protocol was randomly assigned to kits from each litter. For conditioning, the same human, wearing a laboratory coat, fed the rabbit kits for 9 days before the cognitive test. The 6-arm radial maze was chosen for its simplicity and ease of use. Normally appearing kits, born after uterine ischemia at 79% or 92% term in New Zealand White rabbits, were compared to naïve kits. On postpartum day 22/23 or 29/30, the 6-arm maze helped determine if the kits recognized the original feeder from bystander (test 1) or the laboratory coat on bystander (test 2). The use of masks of feeder/bystander (test 3) assessed confounding cues. A weighted score was devised to address variability in entry to maze arms, time, and repeated-trial learning. Results: In conditioned kits, both naïve and HI kits exhibited a significant preference for the face of the feeder but not the laboratory coat. Cognitive deficits were minimal in normal-appearing HI kits. Conclusion: The weighted score was amenable to statistical manipulation.

Maze runners: monkeys show restricted Arabic numeral summation during computerized two-arm maze performance

Mazes have been used in many forms to provide compelling results showcasing nonhuman animals’ capacities for spatial navigation, planning, and numerical competence. The current study presented computerized two-arm mazes to four rhesus macaques. Using these mazes, we assessed whether the monkeys could maximize rewards by overcoming mild delays in gratification and sum the values of Arabic numerals. Across four test phases, monkeys used a joystick controller to choose one of two maze arms on the screen. Each maze arm contained zero, one or two Arabic numerals, and any numerals in the chosen maze arm provided the monkeys with rewards equivalent to the value of those numerals. When deciding which arm to enter, monkeys had to consider distance to numerals and numeral value. In some tests, gaining the maximum reward required summing the value of two numerals within a given arm. All four monkeys successfully maximized reward when comparing single numerals and when comparing arms that each contained two numerals. However, some biases occurred that were suboptimal: the largest single numeral and the delay of reward (by placing numerals farther into an arm from the start location) sometimes interfered with the monkeys’ abilities to optimize. These results indicate that monkeys experience difficulties with inhibition toward single, high valence stimuli in tasks where those stimuli must be considered in relation to overall value when represented by symbolic stimuli such as numerals.

European common frogs determine migratory direction by inclination magnetic compass and show diurnal variation in orientation.

Animals can use two variants of the magnetic compass: the 'polar compass' or the 'inclination compass'. Among vertebrates, the compass type has been identified for salmon, mole rats, birds, turtles and urodeles. However, no experiments have been conducted to determine the compass variant in anurans. To elucidate this, we performed a series of field and laboratory experiments on males of the European common frog during the spawning season. In field experiments in a large circular arena, we identified the direction of the stereotypic migration axis for a total of 581 frogs caught during migration from river to pond or in a breeding pond. We also found that motivation of the frogs varied throughout the day, probably to avoid deadly night freezes, which are common in spring. The laboratory experiments were conducted on a total of 450 frogs in a T-maze placed in a three-axis Merritt coil system. The maze arms were positioned parallel to the natural migration axis inferred on the basis of magnetic field. Both vertical and horizontal components of the magnetic field were altered, and frogs were additionally tested in a vertical magnetic field. We conclude that European common frogs possess an inclination magnetic compass, as for newts, birds and sea turtles, and potentially use it during the spring migration. The vertical magnetic field confuses the frogs, apparently as a result of the inability to choose a direction. Notably, diurnal variation in motivation of the frogs was identical to that in nature, indicating the presence of internal rhythms controlling this process.

Feeding behaviour and food choice in three populations of the millipede Glomeris hexasticha Brandt, 1833 (Diplopoda: Glomerida: Glomeridae): intra- and interpopulation laboratory study

Abstract Foraging behaviour, determined by both internal and external factors, requires investment of time and energy. Optimizing the nutritional decisions also influences efficiency during the feeding process and fitness. Feeding behaviour has been poorly investigated in millipedes. Hence, the aims of this study were to test food choice and to explore intra- and interpopulation variability in several sequences of feeding behaviour in millipede Glomeris hexasticha Brandt, 1833 under laboratory conditions. Individuals of G. hexasticha and leaf litter were collected from three populations within Belgrade, Serbia. A feeding experiment was conducted using a cross-shaped experimental maze with oak leaves, small-leaved linden leaves, and moss as potential food sources. The individuals most often chose oak leaves, subsequently moss, while linden leaves were the least preferred. Sexual dimorphism was detected only for the average time spent in maze arms that contained food items in the Ada New Belgrade population and the Hyde Park population. Intrapopulation differences that depended on feeding status and interpopulation differences in some behavioural sequences were detected. We assume that sexual dimorphism in most of the analysed behavioural traits was not detected, because both sexes had to satisfy basic nutritive requirements after the same starvation period. However, research timing may be responsible, at least partially, for the obtained results. Repeating experiments in different periods of the year or using more fresh food or food sources in different phases of the decomposition may give different results. Further, in our experimental design, some unknown preference towards particular maze arms could not be completely excluded.

Effect of Edible Bird’s Nest on Protecting against Cognitive Deficit and Ameliorating Beta‐Amyloid in Hippocampal Rats’ Model of Cerebral Ischemia

Cerebral ischemia has been identified as the primary cause of global mortality, but there is currently no effective therapy for treating this condition. Consequently, the search for novel neuroprotective agents that can guard against stroke remains essential. Recent research has demonstrated the importance of alternative treatments in the pathology of cerebral ischemia leading to vascular dementia. The purpose of this study was to determine the effect of neurocognitive behavior and beta‐amyloid markers in terms of the neuroprotective effects of Edible Bird’s Nest (EBN). Male adult Wistar rats were orally administered EBN at concentrations of 10, 50, and 100 mg/kg for 2 weeks prior to and 3 weeks after middle cerebral artery occlusion surgery to mimic vascular dementia. The rodents were then classified based on their neurological score, beta‐amyloid accumulation, volume of cerebral infarction, and acetylcholinesterase activity. We assessed the animals’ spatial memory and administered the Morris water maze and radial arm maze tests. We found that EBN substantially decreased beta‐amyloid in the hippocampus, decreased acetylcholinesterase activity, and enhanced the animals’ neurological scores and spatial memory. We conclude that EBN contains potential substances that promote learning and memory pathways. However, additional research is still necessary to confirm these findings.

A Method for Assessing Working Memory in Rats Using Controlled Virtual Environment.

Biological part of the investigation: In our study, young healthy Wistar rats aged 6-7 months were used. The initial stage involved habituating the experimental animals to the experimenter over a period of two weeks. The habituation process was conducted in several successive steps. First, the rats were acclimated to wearing a jacket, which is part of the apparatus that holds the animal in the experimental setup. Next, they were familiarized with the fixation system. Following this, the rats were introduced to the treadmill (a sphere), and finally, they were acclimated to the entire setup. Subsequently, the rats were gradually habituated to the virtual maze and the associated reward system through positive reinforcement. This approach helped minimize stress and facilitated their adaptation to the new conditions. The second stage involved exploring the virtual space and learning the features of the virtual maze, including walls, turns, and the end goal. During the learning phase, the animals received positive reinforcement in the form of sugared water from the automatic water dispenser for correctly performed tasks. To navigate the T-maze, the rats used visual cues such as wall color and figures on the wall. At this stage, the rats learned to use virtual space to achieve their goals. Once the rats showed evident progress in learning the virtual environment, we implemented a protocol to assess their working memory. This assessment was based on the time it took for the rats to find the maze arm that provided positive reinforcement.Engineering part of the investigation: The animal is positioned on a foam plastic sphere with a 30 cm radius, using a custom device that allows its head and paws to remain mobile. Bearing fix the sphere in place, enabling the rat to rotate freely around its vertical axis. The rat's forward and backward movements cause the sphere to rotate, simulating a treadmill. The sphere's movements are detected by two infrared sensors (adapted from optical LED mice with USB interfaces) and transmitted to a computer, which generates an image of the virtual environment - a maze with landmarks on its walls. The virtual environment, created using the Unity Real-Time 3D Development Platform, is projected onto a custom-designed dome display containing the sphere and the lab rat. The setup provided the rat with a 360° field of view. In our study, we present a setup that includes a projector, a dome display, a sphere (treadmill), a virtual T-maze, motion capture sensors, systems for securing animals to the sphere, and positive reinforcement delivery systems. We have developed an optimal protocol for immersing laboratory animals into a virtual environment and evaluating their cognitive functions, particularly working memory. The application of virtual reality in biological experiments enables more precise control over study conditions and allows for the creation of highly accurate and realistic behavioral protocols to assess cognitive functions in animals. This approach enhances our understanding of the mechanisms underlying working memory and their relationship with behavioral processes in rats and other animals.

Contemporary comprehensive approaches to assessing the effectiveness of experimental model of neurodegenerative disorders with cognitive status changes

Aim of the study was to characterize the locomotor and cognitive aspects of the behavior of experimental rats under intracerebroventricular colchicine administration in the open field test and the 8-arm radial maze, as well as identify a set of behavioral features of experimental animals that emerged during the study.&#x0D; Materials and methods. The study was conducted in two stages on 20 male Wistar rats aged 10–11 months. The first stage involved assessment of initial locomotor activity and cognitive functions in all intact rats. At the next stage, the rats were divided into two experimental groups (n = 10): the first group with intracerebroventricular injection of physiological NaCl solution, and the second group with intracerebroventricular injection of colchicine. In 14 days after the surgery, repeated recording of locomotive and cognitive activity indicators was performed.&#x0D; Results. The locomotor activity characteristics did not statistically differ between the animals before the surgical procedures and the rats of the first group. However, in the second group, the activity indicators were significantly higher than in the respective pre-surgery rats. In the intergroup comparison of the rats that entered the second stage of the experiment, it was found that among all the investigated parameters, only the indicator of high activity duration was significantly higher in the second group compared to the first group. At the same time, the animals in the second group showed significant cognitive impairments compared to the first group, as indicated by significantly lower memory index values, the number of correct entries into the maze arms, and a significantly longer time to make the first correct entry into the maze arm.&#x0D; Conclusions. Intracerebroventricular administration of colchicine to experimental rats is accompanied by increased locomotor activity and impairment of cognitive functions. The administration of a physiological solution is not accompanied by a statistically significant increase in locomotor activity, but it demonstrates a clear tendency to increase, which may indicate a certain influence of the procedure itself. The applied pharmacological model of neurodegeneration with subsequent comprehensive assessment of animal behavior in an open field and an 8-arm radial maze is legitimate and can be used to study the early development of neuroinflammation, neuroapoptosis, and synaptogenesis disorders in the experiment.

Effect of Diet on Cognitive Function and Gut Microbiota in Aged Rats.

AbstractBackgroundMany patients with mild cognitive impairment and Alzheimer’s disease have alterations in the gut microbiota. Dietary consumption directly modulates gut microbiota; therefore, the quality of a diet may impact cognitive function and susceptibility to memory impairments. We hypothesized that consumption of the Mediterranean diet (MeDi) versus the Western diet (WD) will improve cognitive function through beneficial changes to the gut microbiota.MethodTwelve‐month‐old male Fischer 344 rats (n = 14/group) were randomly assigned to a MeDi, WD, or Chow diet (positive control to MeDi) for three months. Animals then underwent neurobehavioral assessments (n = 10/group) including the Morris water maze and radial arm water maze to assess aspects of short‐ and long‐term memory. Data were analyzed via One‐ or Two‐Way Repeated Measures ANOVA where appropriate. Fecal samples were collected prior to the behavior. Microbial composition was determined by 16S rRNA sequencing.ResultThe MeDi and WD groups consumed more kcals (p&lt;0.05) at various weeks and weighed more compared to the chow group (p&lt;0.05). There was no difference in time to reach the platform between the MeDi and WD or Chow groups in the Morris water maze, however, animals consuming the chow diet were quicker to reach the platform compared to the WD (p = 0.046). There were no differences in total errors measured by the radial arm water maze (p = 0.50) between diets. Gut microbiota composition (β‐diversity) was distinct between diets (Weighted and Unweighted UniFrac, p&lt;0.001).ConclusionThere were no differences in short‐ or long‐term memory in aged animals consuming a MeDi or WD for three months. Diet‐modulated the gut microbiota as exhibited by differences in β‐diversity between the MeDi, WD, and Chow. As animals consumed a chow diet throughout their lifespan, the MeDi or WD may need to be started earlier in life to exhibit differences. Funding: NIH Mentoring Research Excellence in Aging and Regenerative Medicine5P20GM103629‐10

Effects of low-level RF fields reveal complex pattern of magnetic input to the avian magnetic compass

The avian magnetic compass can be disrupted by weak narrow-band and broadband radio-frequency (RF) fields in the lower MHz range. However, it is unclear whether disruption of the magnetic compass results from the elimination of the perception pattern produced by the magnetic field or from qualitative changes that make the pattern unrecognizable. We show that zebra finches trained in a 4-arm maze to orient relative to the magnetic field are disoriented when tested in the presence of low-level (~ 10 nT) Larmor-frequency RF fields. However, they are able to orient when tested in such RF fields if trained under this condition, indicating that the RF field alters, but does not eliminate, the magnetic input. Larmor-frequency RF fields of higher intensities, with or without harmonics, dramatically alter the magnetic compass response. In contrast, exposure to broadband RF fields in training, in testing, or in both training and testing eliminates magnetic compass information. These findings demonstrate that low-level RF fields at intensities found in many laboratory and field experiments may have very different effects on the perception of the magnetic field in birds, depending on the type and intensity of the RF field, and the birds’ familiarity with the RF-generated pattern.

Abstract 15835: Inhibition of Soluble Epoxide Hydrolase Reduces Cognitive Impairment and Improves Cerebral Hemodynamics in AD/ADRD

Alzheimer's Disease and Alzheimer's Disease-Related Dementias (AD/ADRD) is an emerging global healthcare crisis. However, underlying mechanisms have not been understood well enough to translate into precision medicine. Recent human genetic evidence indicated that soluble hydrolase (sEH) is linked to AD/ADRD. Inhibition of sEH has been reported to improve cognition in AD mice due to its anti-inflammatory and neuronal protective effects. Here, we examined whether inhibition of sEH with TPPU could reduce cognitive impairments by improving cerebral hemodynamics in 18-month-old diabetes (DM)-related ADRD rats and 6 months of TgF344-AD rats. The myogenic responses of the middle cerebral artery (MCA) were impaired in both AD and ADRD rats and were normalized with TPPU. The inner diameters of MCA increased by 49.16 ± 17.02 % in DM rats but decreased by 16.06 ± 2.46% and 11.24 ± 0.05% in age-matched control and TPPU-treated DM rats when pressure was elevated from 40 to 180 mmHg. Similarly, TPPU-treated AD rats significantly enhanced the MCA constriction by 25%. Forced dilatation occurred at pressures &gt; 140 mmHg in MCAs in both rats and was rescued with TPPU treatment. Endothelial denuded MCAs from TPPU-treated DM rats constricted to 75.15 ± 4.25 % at a perfusion pressure of 140 mmHg and further constricted to 74.66 ± 4.01 % at 180 mmHg, compared to dilation of 155.48 ± 17.35 % and 172.78 ± 13.36 % in DM rats at the same pressures. The percentage of time spent with the novel object was 43.32 ± 8.04% and 83.23 ± 8.70% in DM and TPPU-treated DM rats, versus 75.68 ± 3.33% in non-DM rats. Impaired learning and short and long-term memory function examined with an 8-arm water maze in both DM and AD rats were rescued with TPPU treatment. These results provide the first evidence demonstrating that inhibition of sEH reverses cerebrovascular dysfunction and cognitive impairments in AD/ADRD.

Effect of Acute and Chronic Sleep Deficit on Working and Long-Term Memory in Rats

It is known that insufficient sleep or diurnal rhythm disturbances of sleep and wakefulness exert a detrimental effect on cognitive functions. It was thought for a long period that memory consolidation is the most vulnerable link, i.e., information transfer from short-term/working memory to long-term memory. However, there is a progressive number of studies indicating that the most negative consequences of sleep loss are observed in working memory. In our study, we undertook an effort to assess possible disturbances in working memory and long-term memory following sleep loss impact with different protocols in acute and chronic experiment in rats. Sleep in Wistar rats was deprived/restricted by swinging platform technique according to the following protocols: 1 – total sleep deprivation for 18 h; 2 – partial sleep restriction for 24 h (3 h of sleep deprivation alternated with 1 h of sleep opportunity – totally 18 h of sleep deprivation); 3 – chronic partial sleep restriction (conditions 2 for five consistent days). Total sleep deprivation in Y-maze test was shown to result in a significant decrease in spontaneous alternations of maze arms that indicates working memory impairment. This impact in Barnes test did not exert an effect on long-term memory – time spent for seeking a shelter did not change in this task. Acute and chronic sleep restriction induced no changes in working memory and long-term memory. The results obtained allow us to come to conclusion that working memory (in contrast to long-term memory) is a vulnerable component of cognitive function under total sleep deprivation conditions. This negative effect was abolished if periods of sleep deprivation alternated with short periods of sleep opportunities that indicate protective significance of short sleep periods for cognitive functions during sleep deficit. Hence, short-term sleep is helpful for cognitive health and protects working memory, whereas continuous long-term wakefulness impairs it.

Effect of apparatus characteristics on anxiety-like behavior in young adult and old mice of both sexes assessed by the elevated plus maze assay.

Incidence of anxiety-like disorders in humans has been shown to decrease with aging; however, it is still under debate whether there are similarities in mice, which would support the use of mouse models in understanding the neuronal network changes that regulate anxiety-like behavior in aging. One of the most common tests used to assess anxiety-like behavior in laboratory animals is the elevated plus maze (EPM). Although several variables, such as room brightness and width of the maze arms, have been shown to influence the spontaneous animal behavior during the EPM test, none of these variables have ever been evaluated in aging to understand their possible differential effect on younger and older mice. We therefore decided to investigate the effect of apparatus construction on young adult and old mice of both sexes on EPM test performance. Our results show that distance traveled during the test is the variable that is most affected by apparatus characteristics independent of age and sex. We also found that apparatus construction was key in demonstrating that old mice spent more time and had relatively more entries in the open arms as compared to young mice, suggesting a decrease in anxiety-like behavior with age. Taken together, our data demonstrate that EPM apparatus characteristics dramatically affect test outcome with a wider arm apparatus being more effective in revealing age-dependent changes in anxiety-like behavior, thus, suggesting the use of a wider arm EPM when conducting aging studies in mice.

Learning and laterality in wild-caught Namaqua rock mice (Micaelamys namaquensis)

Individuals often exhibit differences in cognition and/or preferences for one side over the other. Such differences have been attributed to the mating system and lateralization of the brain hemispheres that can differ between the sexes, respectively. Despite the hypothesized significant effects on fitness, only a limited number of rodent studies addresses sex differences in laterality and most focus on laboratory rodents. Here we examined whether wild-caught Namaqua rock mice (Micaelamys namaquensis), a rodent widespread in sub-Saharan Africa, exhibit sex differences in learning and laterality in a T-maze. Food-deprived animals entered the maze significantly faster over subsequent learning trials, suggesting that the sexes learned to find the food reward at the end of the maze arms equally. Although we could not confirm a side preference at the population level, the animals were strongly lateralized at an individual level. When the sexes were considered separately, females exhibited a preference for the right maze arm while the opposite was observed in males. The lack of comparable studies of sex-specific lateralization patterns in rodents makes the generalization of our results challenging and highlights the need for more such studies in rodents at both the individual and population levels.

Derivatives of 3, 4, 5-Trimethoxycinnamic Acid Ameliorate Stress-Induced Anxiety in Mice and Rats.

Stress is an overwhelming problem associated with neuronal damage leading to anxiety and depression. The compound 3, 4, 5-trimethoxycinnamic acid (TMCA) has shown anti-stress effects; however, its derivatives remained unknown for their anxiolytic properties. Here, therefore, we investigated derivatives of TMCA (dTMCA) for their anxiolytic effects using immobilization and electric shock-induced stress in rats. Derivatives of TMCA ameliorated anxiety in mice and rats revealed by extended period of time spent in the open arms of elevated plus maze. Stress-mediated repression of tyrosine hydroxylase (TH) protein expression in the amygdala regions of rat brain and dopamine levels in the PC12 cells was restored by two selected derivatives (TMCA#5 and TMCA#9). Unlike TH expression, stress-induced protein expression of phospho-extracellular signal-regulated kinase (pERK) was unaffected by both derivatives in rats. Given the preferential inhibitory activity of dTMCA on dopamine and serotonin receptors, serotonergic road map of cellular signaling could be their target for anxiolytic effects. Thus, dTMCA would be promising agents to prevent neuronal damage associated with rampant stressful conditions.