Swim Task Research Articles

Traumatic Brain Injury in Mice Generates Early-Stage Alzheimer's Disease Related Protein Pathology that Correlates with Neurobehavioral Deficits.

Traumatic brain injury (TBI) increases the long-term risk of neurodegenerative diseases, including Alzheimer's disease (AD). Here, we demonstrate that protein variant pathology generated in brain tissue of an experimental TBI mouse model is similar to protein variant pathology observed during early stages of AD, and that subacute accumulation of AD associated variants of amyloid beta (Aβ) and tau in the TBI mouse model correlated with behavioral deficits. Male C57BL/6 mice were subjected to midline fluid percussion injury or to sham injury, after which sensorimotor function (rotarod, neurological severity score), cognitive deficit (novel object recognition), and affective deficits (elevated plus maze, forced swim task) were assessed post-injury (DPI). Protein pathology at 7, 14, and 28 DPI was measured in multiple brain regions using an immunostain panel of reagents selectively targeting different neurodegenerative disease-related variants of Aβ, tau, TDP-43, and alpha-synuclein. Overall, TBI resulted in sensorimotor deficits and accumulation of AD-related protein variant pathology near the impact site, both of which returned to sham levels by 14 DPI. Individual mice, however, showed persistent behavioral deficits and/or accumulation of toxic protein variants at 28 DPI. Behavioral outcomes of each mouse were correlated with levels of seven different protein variants in ten brain regions at specific DPI. Out of 21 significant correlations between protein variant levels and behavioral deficits, 18 were with variants of Aβ or tau. Correlations at 28 DPI were all between a single Aβ or tau variant, both of which are strongly associated with human AD cases. These data provide a direct mechanistic link between protein pathology resulting from TBI and the hallmarks of AD.

Analysis of Kinematic and Muscular Fatigue in Long-Distance Swimmers.

Muscle fatigue is a complex phenomenon that is influenced by the type of activity performed and often manifests as a decline in motor performance (mechanical failure). The purpose of our study was to investigate the compensatory strategies used to mitigate mechanical failure. A cohort of 21 swimmers underwent a front-crawl swimming task, which required the consistent maintenance of a constant speed for the maximum duration. The evaluation included three phases: non-fatigue, pre-mechanical failure, and mechanical failure. We quantified key kinematic metrics, including velocity, distance travelled, stroke frequency, stroke length, and stroke index. In addition, electromyographic (EMG) metrics, including the Root-Mean-Square amplitude and Mean Frequency of the EMG power spectrum, were obtained for 12 muscles to examine the electrical manifestations of muscle fatigue. Between the first and second phases, the athletes covered a distance of 919.38 ± 147.29 m at an average speed of 1.57 ± 0.08 m/s with an average muscle fatigue level of 12%. Almost all evaluated muscles showed a significant increase (p < 0.001) in their EMG activity, except for the latissimus dorsi, which showed a 17% reduction (ES 0.906, p < 0.001) during the push phase of the stroke cycle. Kinematic parameters showed a 6% decrease in stroke length (ES 0.948, p < 0.001), which was counteracted by a 7% increase in stroke frequency (ES -0.931, p < 0.001). Notably, the stroke index also decreased by 6% (ES 0.965, p < 0.001). In the third phase, characterised by the loss of the ability to maintain the predetermined rhythm, both EMG and kinematic parameters showed reductions compared to the previous two phases. Swimmers employed common compensatory strategies for coping with fatigue; however, the ability to maintain a predetermined motor output proved to be limited at certain levels of fatigue and loss of swimming efficiency (Protocol ID: NCT06069440).

Learning to swim efficiently in a nonuniform flow field.

Microswimmers can acquire information on the surrounding fluid by sensing mechanical queues. They can then navigate in response to these signals. We analyze this navigation by combining deep reinforcement learning with direct numerical simulations to resolve the hydrodynamics. We study how local and nonlocal information can be used to train a swimmer to achieve particular swimming tasks in a nonuniform flow field, in particular, a zigzag shear flow. The swimming tasks are (1) learning how to swim in the vorticity direction, (2) learning how to swim in the shear-gradient direction, and (3) learning how to swim in the shear-flow direction. We find that access to laboratory frame information on the swimmer's instantaneous orientation is all that is required in order to reach the optimal policy for tasks (1) and (2). However, information on both the translational and rotational velocities seems to be required to accomplish task (3). Inspired by biological microorganisms, we also consider the case where the swimmers sense local information, i.e., surface hydrodynamic forces, together with a signal direction. This might correspond to gravity or, for microorganisms with light sensors, a light source. In this case, we show that the swimmer can reach a comparable level of performance to that of a swimmer with access to laboratory frame variables. We also analyze the role of different swimming modes, i.e., pusher, puller, and neutral.

Stress Induces Prolonged Pain Recovery After Surgery: Involvement of Glucocorticoid-Related Pathway.

Increasing evidence suggests that chronic stress increases pain sensitivity and exacerbates existing pain. However, whether and how chronic unpredictable stress (CUS) affects surgical pain is unclear. A postsurgical pain model was performed by longitudinal incision from 0.3 cm of the proximal edge of the heel toward the toes. The skin was sutured, and the wound site was covered. Sham surgery groups underwent the same procedure without an incision. The short-term CUS procedure was conducted by exposure of mice to 2 different stressors each day for 7 days. The behavior tests were conducted between 9:00 am and 4:00 pm. Mice were killed on day 19, and the mouse bilateral L4/5 dorsal root ganglia, spinal cord, anterior cingulate and insular cortex, and amygdala were collected for immunoblot analyses. Presurgical exposure of mice to CUS every day for 1-7 days showed significant depression-like behavior as evidenced by reduced sucrose preference in the sucrose consumption test and prolonged immobility time in the forced swimming task. This short-term CUS procedure did not affect the basal nociceptive response to mechanical and cold stimuli in the Von Frey and acetone-induced allodynia tests, but it delayed pain recovery after surgery, as indicated by the prolonged hypersensitivity in mechanical and cold stimuli by 12 days. The subsequent studies demonstrated that this CUS caused an increase in adrenal gland index. The abnormalities in pain recovery and adrenal gland index after surgery were reversed by a glucocorticoid receptor (GR) antagonist RU38486. Moreover, the prolonged pain recovery after surgery induced by CUS seemed to involve an increase in GR expression and decreases in cyclic adenosine monophosphate, phosphorylated cAMP response element binding protein, and brain-derived neurotrophic factor levels in emotion-related brain regions, such as anterior cingulate and insular cortex, amygdala, dorsal horn, and dorsal root ganglion. This finding indicates that stress-induced GR change may result in dysfunction of GR-related neuroprotective pathway.

Narrowing the coordination solution space during motor learning standardizes individual patterns of search strategy but diversifies learning rates

Constraints on practice can benefit motor learning by guiding the learner towards efficient coordination patterns, but can also narrow the potential solution space of coordination and control. The aim of this paper was to investigate whether narrowing the solution space through more restrictive task constraints limits the expression of potential exploratory behaviours during the learning process, identified using Drifting Markov Models. In a breaststroke swimming task, the change in interlimb coordination of 7 learners practicing for 16 lessons over 2 months was analysed to quantify motor exploration and identify periods of metastable regimes of coordination. Results showed that the observed exploratory dynamics were highly individual both in terms of range of exploration and in the patterns of search. The more restrictive task constraints did not impair the amount of exploration but rather channelled the exploration around a few selected patterns. In addition, restraining the nature of the exploratory process increased the inter-individual differences of the learning rate. Although manipulating the task constraints during learning can help learners to escape from the behavioural consequences of their intrinsic dynamics, maintaining a broad solution space for a diversity of coordination patterns to emerge was key to fostering effective exploration of individual coordination solutions.

Chronic Stress Exacerbates Hyperglycemia-Induced Affective Symptoms in Male Mice

Introduction: Among chronically ill populations, affective disorders remain underdiagnosed and undertreated. A high degree of comorbidity exists between diabetes and affective disorders, particularly depression and anxiety. The mechanisms underlying stress-induced affective dysregulation are likely distinct from those induced by diabetes. A direct comparison between stress- and hyperglycemia-induced affective dysregulation could provide insight into distinct mechanistic targets for depression/anxiety associated with these different conditions. Methods: To this end, the present study used male C57BL/6J mice to compare the independent and combined behavioral and neuroinflammatory effects of two models: (1) unpredictable chronic mild stress and (2) pharmacologically induced hyperglycemia. Results: Streptozotocin-induced hyperglycemia was associated with a set of behavioral changes reflective of the neurovegetative symptoms of depression (i.e., reduced open field activity, reduced grooming, increased immobility in the forced swim task, and decreased marble burying), increased hippocampal Bdnf and Tnf expression, and elevations in frontal cortex Il1b expression. Our chronic stress protocol produced alterations in anxiety-like behavior and decreased frontal cortex Il1b expression. Discussion: While the combination of chronic stress and hyperglycemia produced limited additive effects, their combination exacerbated total symptom burden. Overall, the data indicate that stress and hyperglycemia induce different symptom profiles via distinct mechanisms.

Behavioral context improves optogenetic stimulation of transplanted dopaminergic cells in unilateral 6-OHDA rats

Stem cell therapy has long been a popular method of treatment for Parkinson’s disease currently being researched in both preclinical and clinical settings. While early clinical results are based upon fetal tissue transplants rather than stem cell transplants, the lack of successful integration in some patients and gradual loss of effect in others suggests a more robust protocol is needed. We propose a two-front approach, one where transplants are directly stimulated in coordination with host activity elicited by behavioral tasks, which we refer to as behavioral context. After a pilot with unilateral 6-OHDA rats transplanted with dopaminergic cells differentiated from mesenchymal stem cells that were optogenetically stimulated during a swim task, we discovered that early stimulation predicted lasting reduction of motor deficits, even in the absence of later stimulation. This led to a follow-up with n = 21 rats split into three groups: one stimulated while performing a swim task (Stim-Swim; St-Sw), one not stimulated while swimming (NoStim-Swim; NSt-Sw), and one stimulated while stationary in a bowl (Stim-NoSwim; St-NSw). After initial stimulation (or lack thereof), all rats were retested two and seven days later with the swim task in the absence of stimulation. The St-Sw group gradually achieved and maintained symmetrical limb use, whereas the NSt-Sw group showed persistent asymmetry and the St-NSw group showed mixed results. This supports the notion that stem cell therapy should integrate targeted stimulation of the transplant with behavioral stimulation of the host tissue to encourage proper functional integration of the graft.

Acute gut inflammation reduces neural activity and spine maturity in hippocampus but not basolateral amygdala

Gastrointestinal tract (gut) inflammation increases stress and threat-coping behaviors, which are associated with altered activity in fear-related neural circuits, such as the basolateral amygdala and hippocampus. It remains to be determined whether inflammation from the gut affects neural activity by altering dendritic spines. We hypothesized that acute inflammation alters dendritic spines in a brain region-specific manner. Here we show that acute gut inflammation (colitis) evoked by dextran sodium sulfate (DSS) did not affect the overall spine density in the CA1 region of hippocampus, but increased the relative proportion of immature spines to mature spines on basal dendrites of pyramidal neurons. In contrast, in animals with colitis, no changes in spine density or composition on dendrites of pyramidal cells was observed in the basolateral amygdala. Rather, we observed decreased spine density on dendrites of stellate neurons, but not the relative proportions of mature vs immature spines. We used cFos expression evoked by the forced swim task as a measure of neural activity during stress and found no effect of DSS on the density of cFos immunoreactive neurons in basolateral amygdala. In contrast, fewer CA1 neurons expressed cFos in mice with colitis, relative to controls. Furthermore, CA1 cFos expression negatively correlated with active stress-coping in the swim task and was negatively correlated with gut inflammation. These data reveal that the effects of acute gut inflammation on synaptic remodeling depend on brain region, neuronal phenotype, and dendrite location. In the hippocampus, a shift to immature spines and hypoactivity are more strongly related to colitis-evoked behavioral changes than is remodeling in basolateral amygdala.

"The wrong tools for the right job": a critical meta-analysis of traditional tests to assess behavioural impacts of maternal separation.

Unconditioned tasks in rodents have been the mainstay of behavioural assessment for decades, but their validity and sensitivity to detect the behavioural consequences of early life stress (ELS) remains contentious and highly variable. In the present study, we carried out a meta-analysis to investigate whether persistent behavioural effects, as assessed using unconditioned procedures in rats, are a reliable consequence of early repeated maternal separation, a commonly used procedure in rodents to study ELS. A literature search identified 100 studies involving maternally separated rats and the following unconditioned procedures: the elevated plus maze (EPM); open field test (OFT); sucrose preference test (SPT) and forced swim task (FST). Studies were included for analysis if the separation of offspring from the dam was at least 60min every day during the pre-weaning period prior to the start of adolescence. Our findings show that unconditioned tasks are generally poor at consistently demonstrating differences between control and separated groups with pooled effect sizes that were either small or non-existent (EPM: Hedge's g =  - 0.35, p = 0.01, OFT: Hedge's g =  - 0.32, p = 0.05, SPT: Hedge's g =  - 0.33, p = 0.21, FST: Hedge's g = 0.99, p = 0.0001). Despite considerable procedural variability between studies, heterogeneity statistics were low; indicating the lack of standardization in the maternal separation protocol was the not the cause of these inconsistent effects. Our findings indicate that in general, unconditioned tests of depression and anxiety are not sufficient to reveal the full behavioural repertoire of maternal separation stress should not be relied upon in isolation. We argue that more objective tasks that sensitively detect specific cognitive processes are better suited for translational research on stress-related disorders such as depression.

Tag-based estimates of bottlenose dolphin swimming behavior and energetics.

Current estimates of marine mammal hydrodynamic forces tend to be made using camera-based kinematic data for a limited number of fluke strokes during a prescribed swimming task. In contrast, biologging tag data yield kinematic measurements from thousands of strokes, enabling new insights into swimming behavior and mechanics. However, there have been limited tag-based estimates of mechanical work and power. In this work, we investigated bottlenose dolphin (Tursiops truncatus) swimming behavior using tag-measured kinematics and a hydrodynamic model to estimate propulsive power, work and cost of transport. Movement data were collected from six animals during prescribed straight-line swimming trials to investigate swimming mechanics over a range of sustained speeds (1.9-6.1 m s-1). Propulsive power ranged from 66 W to 3.8 kW over 282 total trials. During the lap trials, the dolphins swam at depths that mitigated wave drag, reducing overall drag throughout these mid- to high-speed tasks. Data were also collected from four individuals during undirected daytime (08:30-18:00h) swimming to examine how self-selected movement strategies are used to modulate energetic efficiency and effort. Overall, self-selected swimming speeds (individual means ranging from 1.0 to 1.96 m s-1) tended to minimize cost of transport, and were on the lower range of animal-preferred speeds reported in literature. The results indicate that these dolphins moderate propulsive effort and efficiency through a combination of speed and depth regulation. This work provides new insights into dolphin swimming behavior in both prescribed tasks and self-selected swimming, and presents a path forward for continuous estimates of mechanical work and power from wild animals.

Depression-related phenotypes at early stages of Aβ and tau accumulation in inducible Alzheimer's disease mouse model: Task-oriented and concept-driven interpretations

Depression is highly prevalent in Alzheimer Disease (AD); however, there is paucity of studies that focus specifically on the assessment of depression-relevant phenotypes in AD mouse models. Conditional doxycycline-dependent transgenic mouse models reproducing amyloidosis (TetOffAPPsi) and/or tau (TetOffTauP301L) pathology starting at middle age (6 months) were used in this study. As AD patients can experience depressive symptoms relatively early in disease, testing was conducted at early, pre-pathology stages of Aβ and/or tau accumulation (starting from 45 days of transgenes expression). Tau-related differences were detected in the Novelty Suppressed Feeding task (NSF), whereas APP-related differences were observed predominantly in measures of the Open Field (OF) and Forced Swim tasks (FST). Effects of combined production of Aβ and tau were detected in immobility during the 1st half of the Tail Suspension task (TST). These data demonstrate that results from different tasks are difficult to reconcile using task/variable-centered interpretations in which a single task/variable is assigned an ad-hoc meaning relevant to depression. An alternative, concept-oriented, approach is based on multiple variables/tests, with an understanding of their possible inter-dependence and utilization of statistical approaches that handle correlated data sets. The existence of strong correlations within and between some of the tasks supported utilization of factor analyses (FA). FA explained a similar amount of variability across the genotypes (∼80%) and identified two factors stable across genotypes and representing motor activity and anxiety measures in OF. In contrast, variables related to FST, TST, and NSFT did not demonstrate a structure of factor loadings that would support the existence of a single integral factor of "depressive state" measured by these tasks. In addition, factor loadings varied between genotypes, indicating that genotype-specific between-task correlations need to be considered for interpretations of findings in any single task. In general, this study demonstrates that utilization of multiple tasks to characterize behavioral phenotypes, an approach that is finally gaining more widespread adoption, requires a step of data integration across different behavioral tests for appropriate interpretations.

Soft Underwater Swimming Robots Based on Artificial Muscle

AbstractWith the increasing requirements of underwater missions and the rapid development of soft robotics technologies, soft underwater swimming robots have become a hot topic of research due to their low noise, high flexibility, and high environmental adaptability. In the past 10 years, research into soft underwater robots based on artificial muscle actuation has made considerable progress. Herein, a comprehensive survey on recent advances in soft underwater swimming robots based on different actuation methods is reviewed systematically, including pressure actuation, intelligent material actuation, and biomaterial actuation. First, for each type of actuation, the actuating principle, structural design, and swimming performance of soft underwater robots are introduced in detail. Then, according to the different swimming modes of underwater organisms, the aforementioned soft underwater robots are classified and compared. The results show that for different swimming tasks and application scenarios, the robot needs to realize the optimal design by reasonably selecting the actuating method and the swimming mode. This review summarizes the advanced information and critical technology in designing high‐performance soft underwater robots in the aspect of structural design, actuating methods, and swimming modes and offers an insightful outlook for the future development of soft robots.

Lithium produces bi-directionally regulation of mood disturbance, acts synergistically with anti-depressive/-manic agents, and did not deteriorate the cognitive impairment in murine model of bipolar disorder

Lithium (Li) is a well-established mood disorder treatment and may be neuroprotective. Bi-directional regulation (i.e. affecting manic symptoms and depressive symptoms) by Li has not been demonstrated. This study explored: (1) bidirectional regulation by Li in murine models of depression, mania, and bipolar disorder (BP); and (2) potential Li synergism with antidepressant/anti-mania agents. The chronic unpredictable mild stress (CUMS) and ketamine-induced mania (KM) models were used. These methods were used in series to produce a BP model. In vivo two-photon imaging was used to visualize Ca2+ activity in the dorsolateral prefrontal cortex. Depressiveness, mania, and cognitive function were assessed with the forced swim task (FST), open field activity (OFA) task, and novel object recognition task, respectively. In CUMS mice, Ca2+ activity was increased strongly by Li and weakly by lamotrigine (LTG) or valproate (VPA), and LTG co-administration reduced Li and VPA monotherapy effects; depressive immobility in the FST was attenuated by Li or LTG, and attenuated more strongly by LTG-VPA or LTG-Li; novel object exploration was increased strongly by Li and weakly by LTG-Li, and reduced by LTG, VPA, or LTG-VPA. In KM mice, Li or VPA attenuated OFA mania symptoms and normalized Ca2+ activity partially; Li improved cognitive function while VPA exacerbated the KM alteration. These patterns were replicated in the respective BP model phases. Lithium had bi-directional, albeit weak, mood regulation effects and a cognitive supporting effect. Li co-administration with antidepressant/-manic agents enhanced mood-regulatory efficacy while attenuating their cognitive-impairing effects.

The protocol for assessing olfactory working memory capacity in mice.

BackgroundWorking memory capacity (WMC) is the ability to maintain information over a few seconds. Although it has been extensively studied in healthy subjects and neuropsychiatric patients, few tasks have been developed to measure such changes in rodents. Many procedures have been used to measure WM in rodents, including the radial arm maze, the WM version of the Morris swimming task, and various delayed matching and nonmatching‐to‐sample tasks. It should be noted, however, that the memory components assessed in these procedures do not include memory capacity.MethodsWe developed an olfactory working memory capacity (OWMC) paradigm to assess the WMC of 3‐month‐old 5×FAD mice, a mouse model of Alzheimer's disease. The task is divided into five phases: context adaptation, digging training, rule learning for nonmatching to a single sample odor (NMSS), rule learning for nonmatching to multiple sample odors (NMMS), and capacity testing.ResultsIn the NMSS rule‐learning phase, there was no difference between wild‐type (WT) mice and 5×FAD mice in the performance correct rate, correct option rate, and correct rejection rate. The WT mice and 5×FAD mice showed similar memory capacity in the NMMS rule‐learning phase. After capacity test, we found that the WMC was significantly diminished in 5×FAD mice. As the memory load increased, 5×FAD mice also made significantly more errors than WT mice.ConclusionThe OWMC task, based on a nonmatch‐to‐sample rule, is a sensitive and robust behavioral assay that we validated as a reliable method for measuring WMC and exploring different components of memory in mice.

Assessment of VO2 Max Reliability with Garmin Smart Watch among Swimmers

Maximal aerobic capacity (VO2  max) is one of the important factors that influence swimming performance. Currently, the Garmin Forerunner Fitness Watch 935 used to measure VO2  max are expensive, require skilled-trained personnel, not feasible for large-scale use, and land-based, which will not be accurate in measuring water-based activity. In order to measure the swimming performance, there is a need for an affordable, feasible, and reliable device. Therefore, the current study aimed to examine the intra- rater reliability of Garmin Forerunner Fitness Watch 935 accuracy in measuring the VO2  max among collegiate swimmers during the 200m swimming task. The VO2  max measurement of 10 collegiate swimmers was taken with Garmin Forerunner for two trials. The intra-class correlation coefficient (ICC), standard error of measurements (SEMs), and Bland-Altman plot was used in the current study to establish  the inter-rater  reliability measurement. The intra-rater  reliability  of Garmin  Forerunner  showed high  reliability and accuracy with an intra-class correlation coefficient (2,1) of 0.869 and standard error of measurements of 0.231 ml/kg/min. Further, the results were strengthened with Bland-Altman plot showed an acceptable agreement between the two trials. The Garmin Forerunner would be a simple, objective and useful device to be used by physiotherapists, trainers and other sports-related disciplines to assess and improve the swimming performance by targeting the heart rate and VO2 max.

An external focusing strategy was beneficial in experienced children but not in novices: The effect of external focus, internal focus, and holistic attention strategies

External focus (attention directed to an intended effect) has been shown to improve motor performance compared to internal focus (attention directed to body movements). Recently, holistic attention (attention directed to the overall feeling) has been discussed as an effective alternative. We hypothesized that a less specific cue (e.g. holistic attention) may be more effective than an external focus in experienced individuals. Therefore, the present study examined the effect of external focus, internal focus, and holistic attention on 14 experienced children-athletes ( Mage, 14.35 ± 1.98 years; Mheight, 171.28 ± 9.53 cm; Mweight, 58.28 ± 10.28 kg) and 14 novice children ( Mage, 14.21 ± 1.92 years; Mheight, 170.92 ± 12.40 cm; Mweight, 62.14 ± 15.62 kg). Participants completed a 16-meter front crawl swimming task with assigned instructions for three trials per condition. The results showed main effects of skill level ( p &lt; 0.001), condition ( p = 0.006), and the skill level/condition interaction ( p = 0.003). Post hoc tests revealed that external focus was superior to internal focus ( p &lt; 0.001), with no difference between holistic attention and internal focus ( p = 0.158) or holistic attention and external focus ( p = 0.05) in the experienced athletes, while none of the conditions were different in novices. The benefits of attentional focus may be influenced by the level of experience.

Consequences of Hyperphosphorylated Tau in the Locus Coeruleus on Behavior and Cognition in a Rat Model of Alzheimer's Disease.

The locus coeruleus (LC) is one of the earliest brain regions to accumulate hyperphosphorylated tau, but a lack of animal models that recapitulate this pathology has hampered our understanding of its contributions to Alzheimer's disease (AD) pathophysiology. We previously reported that TgF344-AD rats, which overexpress mutant human amyloid precursor protein and presenilin-1, accumulate early endogenous hyperphosphorylated tau in the LC. Here, we used TgF344-AD rats and a wild-type (WT) human tau virus to interrogate the effects of endogenous hyperphosphorylated rat tau and human tau in the LC on AD-related neuropathology and behavior. Two-month-old TgF344-AD and WT rats received bilateral LC infusions of full-length WT human tau or mCherry control virus driven by the noradrenergic-specific PRSx8 promoter. Rats were subsequently assessed at 6 and 12 months for arousal (sleep latency), anxiety-like behavior (open field, elevated plus maze, novelty-suppressed feeding), passive coping (forced swim task), and learning and memory (Morris water maze and fear conditioning). Hippocampal microglia, astrocyte, and AD pathology were evaluated using immunohistochemistry. In general, the effects of age were more pronounced than genotype or treatment; older rats displayed greater hippocampal pathology, took longer to fall asleep, had reduced locomotor activity, floated more, and had impaired cognition compared to younger animals. TgF344-AD rats showed increased anxiety-like behavior and impaired learning and memory. The tau virus had negligible influence on most measures. Effects of hyperphosphorylated tau on AD-like neuropathology and behavioral symptoms were subtle. Further investigation of different forms of tau is warranted.

Stress reveals a specific behavioral phenotype for opioid abuse susceptibility.

Susceptibility to stress has long been considered important for the development of substance use disorders. Nonetheless, behavioral and physiological responses to stress are highly variable, making it difficult to identify the individuals who are most likely to abuse drugs. In the present study, we employed a comprehensive battery of tests for negative valence behaviors and nociception to identify individuals predisposed to opioid seeking following oral opioid self-administration. Furthermore, we examined how this profile was affected by a history of stress. We observed that mice receiving foot shock stress failed to exhibit a preference for sucrose, showed increased immobility in the forced swim task, and exhibited mechanical hypersensitivity when compared to controls. When considering these behaviors in light of future fentanyl-seeking responses, we observed that heightened mechanical sensitivity corresponded to higher opioid preference in mice with a history of stress, but not controls. Moreover, we were surprised to discover that paradoxically high sucrose preferences predicted fentanyl preference in shock mice, while signs of anhedonia predicted fentanyl preference in controls. Taken together, these results indicate that stress can act as a physiological modulator, shifting profiles of opioid abuse susceptibility depending on an individual's history.

The Effect of Early Life Stress on Emotional Behaviors in GPR37KO Mice.

GPR37 is an orphan G-protein-coupled receptor, a substrate of parkin which is linked to Parkinson’s disease (PD) and affective disorders. In this study, we sought to address the effects of early life stress (ELS) by employing the paradigm of limited nesting material on emotional behaviors in adult GPR37 knockout (KO) mice. Our results showed that, while there was an adverse effect of ELS on various domains of emotional behaviors in wild type (WT) mice in a sex specific manner (anxiety in females, depression and context-dependent fear memory in males), GPR37KO mice subjected to ELS exhibited less deteriorated emotional behaviors. GPR37KO female mice under ELS conditions displayed reduced anxiety compared to WT mice. This was paralleled by lower plasma corticosterone in GPR37KO females and a lower increase in P-T286-CaMKII by ELS in the amygdala. GPR37KO male mice, under ELS conditions, showed better retention of hippocampal-dependent emotional processing in the passive avoidance behavioral task. GPR37KO male mice showed increased immobility in the forced swim task and increased P-T286-CaMKII in the ventral hippocampus under baseline conditions. Taken together, our data showed overall long-term effects of ELS—deleterious or beneficial depending on the genotype, sex of the mice and the emotional context.

Tamsulosin facilitates depressive-like behaviors in mice: Involvement of endogenous glucocorticoids

The benign prostatic hyperplasia (BPH) is the main source of lower urinary tract symptoms. The BPH is a common age‐dependent disease and tamsulosin is an α1-adrenoceptor blocker widely prescribed for BPH. Beyond the common adverse effects of tamsulosin, increased diagnosis of dementia after prescription was observed. Importantly, a clinical study suggested that tamsulosin may exert antidepressant effects in BPH patients. Considering the expression of α1-adrenoceptors in the brain, this study aimed to investigate the effects of tamsulosin in the forced swimming and open field tests in mice. For this, tamsulosin (0.001–1 mg/kg) was orally administered subacutely (1, 5 and 23 hr) and acutely (60 min) before tests. Mifepristone (10 mg/kg), a glucocorticoid receptor antagonist, and aminoglutethimide (10 mg/kg), a streoidogenesis inhibitor, were intraperitoneally injected before tamsulosin to investigate the role of the hypothalamic-pituitary-adrenal axis in the mediation of tamsulosin-induced effects. Subacute and acute administrations of tamsulosin increased the immobility time in the first exposition to an inescapable stressful situation. In the re-exposition to the swim task, controls displayed a natural increase in the immobility time, and the treatment with tamsulosin further increased this behavioral parameter. Tamsuslosin did not affect spontaneous locomotion neither in naïve nor in stressed mice. Our findings also showed that mifepristone and aminoglutethimide prevented the tamsulosin-induced increase in the immobility time in the first and second swimming sessions, respectively. In conclusion, tamsulosin may contribute to increased susceptibility to depressive-like behaviors, by facilitating the acquisition of a passive stress-copying strategy. These effects seem to be dependent on endogenous glucocorticoids.