Highly Ordered Eutectic Mesostructures via Template-Directed Solidification within Thermally Engineered Templates.

Template-directed self-assembly of solidifying eutectics results in emergence of unique microstructures due to diffusion constraints and thermal gradients imposed by the template. Here, the importance of selecting the template material based on its conductivity to control heat transfer between the template and the solidifying eutectic, and thus the thermal gradients near the solidification front, is demonstrated. Simulations elucidate the relationship between the thermal properties of the eutectic and template and the resultant microstructure. The overarching finding is that templates with low thermal conductivities are generally advantageous for forming highly organized microstructures. When electrochemically porosified silicon pillars (thermal conductivity < 0.3 Wm-1K-1) are used as the template into which an AgCl-KCl eutectic is solidified, 99% of the unit cells in the solidified structure exhibit the same pattern. In contrast, when higher thermal conductivity crystalline silicon pillars (≈100 Wm-1K-1) are utilized, the expected pattern is only present in 50% of the unit cells. The thermally engineered template results in mesostructures with tunable optical properties and reflectances nearly identical to the simulated reflectances of perfect structures, indicating highly ordered patterns are formed over large areas. This work highlights the importance of controlling heat flows in template-directed self-assembly of eutectics.

Parvovirus B19 infection after kidney transplantation: A single centre experience.

Background: Parvovirus B19 is an uncommon cause of anaemia in kidney transplant recipients (KTRs). The study aims to determine the incidence, clinical presentation, laboratory findings and outcome of parvovirus B19-related anaemia in KTR. Method: We conducted a 12-year retrospective, single-centre study describing the clinical profile of KTRs with parvovirus B19-related anaemia. Result: Amongst the 714 patients who underwent kidney transplantation between January 2011 and January 2023, (cumulative follow-up: 1287 patient-years), six females and one male, developed parvovirus B19-related anaemia. The incidence proportion (risk) is 0.98% with an incidence rate of 5.43 cases per 1000 patient-year. The median duration from transplant to development of anaemia was 6 weeks (range: 4-40 weeks). The mean fall in haemoglobin was 2.88 ± 1.55 gm/dl; concomitant leukopenia and thrombocytopenia were observed in 57.1 and 28.6% of patients. Three patients responded to a reduction in immunosuppression, the four non-responders required the administration of low-dose intravenous immunoglobulin. The mean duration from initiation of therapy to a sustained rise in haemoglobin was 7.71 ± 2.62 weeks. None of the patients had a relapse of the infection. Conclusions: Parvovirus B19 infection is an uncommon cause of post-transplant refractory anaemia. The key to successfully managing such patients includes a high index of suspicion, early diagnosis and reduction of immunosuppression with or without administration of intravenous immunoglobulin.

Uncertainty evaluation of data acquisition and analysis system relevant to infrared flowing medium laser.

In flowing medium Chemical Oxygen Iodine Laser (COIL), Singlet oxygen is produced by the exothermic reaction of basic hydrogen peroxide solution and chlorine gas. It pumps the iodine and lasing process takes place by stimulated emission. Laser power is extracted using cavity. Development of customized data acquisition system is essential for measurements and analysis of both fundamental (temperature, pressure, level) as well as derived parameters (lasing medium concentration, flow rates of gases and laser power). The focus of the present paper is to dwell on uncertainty evaluation of a complex gas laser source in terms of ascertaining influences of primary/fundamental variables and corresponding derived parameters along with manner of uncertainty propagation. The study facilitates determining the variables with most significant impact on system performance, critical form point of view from optimal functioning of large-scale systems. This enables prediction of overall system uncertainty potentially extendable to other similar laser systems involving subsystems with mutual interdependencies together being distributed over a significantly large laboratory space. The relative combined uncertainty is computed to be 8.3%. The methodology shows significant potential for true decision-making and control of realistic gas laser source operation using developed 150 channel Data Acquisition and Analysis System (DAAS).

Designing Multicomponent Polymer Colloids for Self-Stratifying Films.

Aqueous polymer colloids known as latexes are widely used in coating applications. Multicomponent latexes comprised of two incompatible polymeric species organized into a core-shell particle morphology are a promising system for self-stratifying coatings that spontaneously partition into multiple layers, thereby yielding complex structured coatings requiring only a single application step. Developing new materials for self-stratifying coatings requires a clear understanding of the thermodynamic and kinetic properties governing phase separation and polymeric species transport. In this work, we study phase separation and self-stratification in polymer films based on multicomponent acrylic (shell) and acrylic-silicone (core) latex particles. Our results show that the molecular weight of the shell polymer and heat aging conditions of the film critically determine the underlying transport phenomena, which ultimately controls phase separation in the film. Unentangled shell polymers result in efficient phase separation within hours with heat aging at reasonable temperatures, whereas entangled shell polymers effectively inhibit phase separation even under extensive heat aging conditions over a period of months due to kinetic limitations. Transmission electron microscopy is used to track morphological changes as a function of thermal aging. Interestingly, our results show that the rheological properties of the latex films are highly sensitive to morphology, and linear shear rheology is used to understand morphological changes. Overall, these results highlight the importance of bulk rheology as a simple and effective tool for understanding changes in morphology in multicomponent latex films.

The Food Recognition Benchmark: Using Deep Learning to Recognize Food in Images.

The automatic recognition of food on images has numerous interesting applications, including nutritional tracking in medical cohorts. The problem has received significant research attention, but an ongoing public benchmark on non-biased (i.e., not scraped from web) data to develop open and reproducible algorithms has been missing. Here, we report on the setup of such a benchmark using publicly available food images sourced through the mobile MyFoodRepo app used in research cohorts. Through four rounds, the benchmark released the MyFoodRepo-273 dataset constituting 24,119 images and a total of 39,325 segmented polygons categorized in 273 different classes. Models were evaluated on private tests sets from the same platform with 5,000 images and 7,865 annotations in the final round. Top-performing models on the 273 food categories reached a mean average precision of 0.568 (round 4) and a mean average recall of 0.885 (round 3), and were deployed in production use of the MyFoodRepo app. We present experimental validation of round 4 results, and discuss implications of the benchmark setup designed to increase the size and diversity of the dataset for future rounds.

Solar disinfection - An appropriate water treatment method to inactivate faecal bacteria in cold climates.

Solar disinfection (SODIS) is an inexpensive drinking water treatment method applied in tropical and sub-tropical low-income countries. However, it has been unclear whether it functions adequately also in colder climates. To investigate this issue, SODIS experiments were performed in the humid continental climate of Finland by exposing faecally contaminated drinking water to natural solar radiation at different water temperatures (8-23 °C) and UV intensities (12-19 W/m2) in polyethylene (PE) bags. To establish an adequate benchmark, SODIS experiments with the same experimental design were additionally conducted in the Mediterranean climate of Spain in typical conditions of SODIS application (~39 °C and 42 W/m2). Out of all experiments, the highest coliform and enterococci inactivation efficiencies in terms of lowest required doses for 4-log disinfection (25 Wh/m2 and 60 Wh/m2, respectively) were obtained in humid continental climate at the lowest studied mean water temperature (8-11 °C). Despite the low mean UV irradiance (~19 Wh/m2), 4-log disinfection of coliforms and enterococci were also reached fast in these conditions (1 h 27 min and 3 h 18 min, respectively). Overall, the doses required for disinfection increased as the water temperatures and UV intensities of the experiments rose. Disinfection of 4-logs (> 99.99%) of both bacteria was reached in all SODIS experiments within 6 h, suggesting SODIS could be a sufficient household water treatment method also in colder climates, unlike previously thought. The effects of different water temperatures on bacterial inactivation were also tested in the absence of sunlight. Together the obtained results indicate that while water temperatures below or close to the optima of coliforms and enterococci (~10 °C) alone do not cause inactivation, these temperatures may enhance SODIS performance. This phenomenon is attributed to slower bacterial metabolism and hence slower photorepair induced by the low water temperature.

Measuring Molecular Diffusion Through Thin Polymer Films with Dual-Band Plasmonic Antennas.

A general and quantitative method to characterize molecular transport in polymers with good temporal and high spatial resolution, in complex environments, is an important need of the pharmaceutical, textile, and food and beverage packaging industries, and of general interest to the polymer science community. Here we show how the amplified infrared (IR) absorbance sensitivity provided by plasmonic nanoantenna-based surface enhanced infrared absorption (SEIRA) provides such a method. SEIRA enhances infrared (IR) absorbances primarily within 50 nm of the nanoantennas, enabling localized quantitative detection of even trace quantities of analytes and diffusion measurements in even thin polymer films. Relative to a commercial attenuated total internal reflection (ATR) system, the limit of detection is enhanced at least 13-fold, and as is important for measuring diffusion, the detection volume is about 15 times thinner. Via this approach, the diffusion coefficient and solubility of specific molecules, including l-ascorbic acid (vitamin C), ethanol, various sugars, and water, in both simple and complex mixtures (e.g., beer and a cola soda), were determined in poly(methyl methacrylate), high density polyethylene (HDPE)-based, and polypropylene-based polyolefin films as thin as 250 nm.

TNF signaling via TNF receptors does not mediate the effects of short-term exercise on cognition, anxiety and depressive-like behaviors in middle-aged mice.

BACKGROUND: We recently reported that tumor necrosis factor (TNF) signaling via the TNFR1 and TNFR2 receptors mediates the effects of long-term exercise on locomotion, cognition and anxiety, but not depressive-like behavior. We now investigated whether the TNF signaling via its receptors also mediates the effects of short-term exercise on cognition, anxiety and depressive-like behaviors. METHODS: Thirteen-month-old C57BL/6 (WT), TNF-/-, TNFR1-/-, and TNFR2-/- mice were provided with 4 weeks of voluntary wheel running followed by behavioral testing using an established behavioral battery. Each genotype had a respective non-exercise control. RESULTS: There was no interaction between genotype and exercise in any of the tests but the main effect of genotype, and not exercise, were found to be significant in the open field (OF), forced-swim test (FST) and Barnes maze (BM). In the OF, the control and exercise TNFR2-/- mice spent significantly less time in the inner zone than mice in the control and exercise WT and TNF-/- cohorts. In the FST, control and exercise WT mice showed significantly higher immobility time than their control and exercise TNF-/-, TNFR1-/- and TNFR2-/- cohorts. In the BM, the latency to escape over 4 days of training was significantly higher in all KO groups compared to WT, irrespective of exercise. Also, the latency to escape to the original location during the probe trial was higher for control and exercise WT compared to corresponding TNFR1-/- mice. In contrast, the latency to escape to the new location was lower for control and exercise WT compared to control and exercise TNFR1-/- and TNFR2-/- mice. The latency to escape to the new location in exercise groups was longer compared to control within all genotypes. CONCLUSION: While TNF signaling via the TNF receptors mediates cognition, anxiety and depressive-like behaviors independently, it does not mediate the effects of short-term exercise on these behaviors in middle-aged mice.

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.

Short-Term Environmental Enrichment is a Stronger Modulator of Brain Glial Cells and Cervical Lymph Node T Cell Subtypes than Exercise or Combined Exercise and Enrichment.

Physical exercise (PE) and environmental enrichment (EE) can modulate immunity. However, the differential effects of short-term PE, EE, and PE + EE on neuroimmune mechanisms during normal aging has not been elucidated. Hence, a cohort of 3-, 8-, and 13-month-old immunologically unchallenged C57BL/6 wild-type mice were randomly assigned to either Control, PE, EE, or PE + EE groups and provided with either no treatment, a running wheel, a variety of plastic and wooden objects alone or in combination with a running wheel for seven weeks, respectively. Immunohistochemistry and 8-color flow cytometry were used to determine the numbers of dentate gyrus glial cells, and the proportions of CD4+ and CD8+ T cell numbers and their subsets from cervical lymph nodes, respectively. An increase in the number of IBA1+ microglia in the dentate gyrus at 5 and 10 months was observed after EE, while PE and PE + EE increased it only at 10 months. No change in astroglia number in comparison to controls were observed in any of the treatment groups. Also, all treatments induced significant differences in the proportion of specific T cell subsets, i.e., CD4+ and CD8+ T naïve (TN), central memory (TCM), and effector memory (TEM) cells. Our results suggest that in the short-term, EE is a stronger modulator of microglial and peripheral T cell subset numbers than PE and PE + EE, and the combination of short-term PE and EE has no additive effects.

Duration of Environmental Enrichment Determines Astrocyte Number and Cervical Lymph Node T Lymphocyte Proportions but Not the Microglial Number in Middle-Aged C57BL/6 Mice.

Environmental enrichment (EE) has been shown to modulate behavior and immunity. We recently reported that both short and long-term EE enhance baseline locomotion and alleviate depressive-like behavior, but only long-term EE affects locomotion adversely in a threatening environment and enhances anxiety-like behavior in middle-age mice. We have now investigated whether the observed changes in behavior after short- and long-term EE were associated with underlying immune changes. Hence, at the end of behavioral testing, mice were sacrificed, and brains and cervical lymph nodes were collected to investigate the differential effects of the duration of EE (short- and long-term) on the number of immunopositive glial cells in the dentate gyrus, CA1, CA2, and CA3 regions of the hippocampus and proportions of T cell subsets in the cervical lymph nodes using immunohistochemistry and flow cytometry, respectively. EE, regardless of duration, caused an increase in microglia number within the dentate gyrus, CA1 and CA3 hippocampal regions, but only long-term EE increased astrocytes number within the dentate gyrus and CA3 hippocampal regions. A significantly higher proportion of CD8+ naive T cells was observed after long-term EE vs. short-term EE. No significant differences were observed in the proportion of central memory and effector memory T cells or early activated CD25+ cells between any of the test groups. Our results suggest that EE, irrespective of duration, enhances the numbers of microglia, but long-term EE is required to modify astrocyte number and peripheral T cell proportions in middle-aged mice. Our findings provide new insights into the therapeutic effects of EE on various brain disorders, which may be at least partly mediated by glial and neuroimmune modulation.

Effects of aging on the motor, cognitive and affective behaviors, neuroimmune responses and hippocampal gene expression.

The known effects of aging on the brain and behavior include impaired cognition, increases in anxiety and depressive-like behaviors, and reduced locomotor activity. Environmental exposures and interventions also influence brain functions during aging. We investigated the effects of normal aging under controlled environmental conditions and in the absence of external interventions on locomotor activity, cognition, anxiety and depressive-like behaviors, immune function and hippocampal gene expression in C57BL/6 mice. Healthy mice at 4, 9, and 14 months of age underwent behavioral testing using an established behavioral battery, followed by cellular and molecular analysis using flow cytometry, immunohistochemistry, and quantitative PCR. We found that 14-month-old mice showed significantly reduced baseline locomotion, increased anxiety, and impaired spatial memory compared to younger counterparts. However, no significant differences were observed for depressive-like behavior in the forced-swim test. Microglia numbers in the dentate gyrus, as well as CD8+ memory T cells increased towards late middle age. Aging processes exerted a significant effect on the expression of 43 genes of interest in the hippocampus. We conclude that aging is associated with specific changes in locomotor activity, cognition, anxiety-like behaviors, neuroimmune responses and hippocampal gene expression.

Short-term environmental enrichment, and not physical exercise, alleviate cognitive decline and anxiety from middle age onwards without affecting hippocampal gene expression.

Physical exercise (PE) and environmental enrichment (EE) have consistently been shown to modulate behavior and neurobiological mechanisms. The current literature lacks evidence to confirm the relationship between PE and EE, if any, and whether short-term treatment with PE, EE, or PE+EE could be considered to correct age-related behavioral deficits. Three-, 8-, and 13-month-old C57BL/6 mice were assigned to either PE, EE, or PE+EE treatment groups (n = 12-16/group) for 4 weeks before behavioral testing and were compared to controls. Differential effects of the treatments on various behaviors and hippocampal gene expression were measured using an established behavioral battery and high-throughput qPCR respectively. Short-term EE enhanced locomotor activity at 9 and 14 months of age, whereas the combination of PE and EE reduced locomotor activity in the home cage at 14 months. Short-term EE also was found to reverse the age-related increase in anxiety at 9 months and spatial memory deficits at 14 months of age. Conversely, short-term PE induced spatial learning impairment and depressive-like behavior at four months but showed no effects in 9- and 14-month-old mice. PE and PE+EE, but not EE, modified the expression of several hippocampal genes at 9 months of age compared with control mice. In conclusion, short-term EE may help to alleviate age-related cognitive decline and increase in anxiety, without altering hippocampal gene expression. On the contrary, PE is detrimental at a young age for both affective-like behaviors and spatial learning and memory but showed no effects at middle and late middle age despite hippocampal gene expression alterations.

The effects of short-term and long-term environmental enrichment on locomotion, mood-like behavior, cognition and hippocampal gene expression.

BACKGROUND: Environmental enrichment (EE) has been shown to modulate behavior and hippocampal gene expression; however, the currently available literature does not explain the differential effects that may relate to the duration of EE. AIM: To investigate the differential effects of short- and long-term EE on locomotion, anxiety-, depressive- and cognition-like behaviors, and hippocampal gene expression under physiological conditions. METHODS: We assigned either short-term or long-term intervention with respective controls to healthy C57BL/6 mice (n = 12-16/group). The short-term EE group received EE for four weeks starting at eight months of age, while the long-term EE group received EE for six months starting at three months of age. Differential effects of the duration of EE on various behaviors and hippocampal gene expression at nine months of age were measured using an established behavioral battery and high-throughput RT-qPCR, respectively. RESULTS: Both short-term and long-term EE significantly enhanced locomotion in the home cage and reduced depressive-like behavior in the forced-swim test. Long-term EE, however, reduced locomotion in the open-field test. Additionally, short-term EE reduced the mean body weight and showed anxiolytic effects in the elevated-zero maze (EZM), while these effects were lost after long-term EE. There were no effects of either short-term or long-term EE on the expression of 43 hippocampal genes of interest tested at adjusted p < 0.05. CONCLUSION: Both short and long-term EE are equally beneficial for baseline locomotor activity and depressive-like behavior. However, long-term EE affects locomotion adversely in a threatening environment and is anxiogenic.

Ceasing exercise induces depression-like, anxiety-like, and impaired cognitive-like behaviours and altered hippocampal gene expression.

BACKGROUND: Regular exercise can reduce depression-, anxiety-, and impaired cognitive-like behaviours, and upregulate hippocampal genes associated with neuroplasticity. However, the effects of ceasing exercise on depression-, anxiety-, and cognitive-like behaviours, and hippocampal gene expression remain unknown. METHODS: 12-week-old C57BL/6 mice (n = 12-16/group) were randomised to six months of exercise (exercise (EXC)), four months of exercise then two months of no exercise (exercise-cessation (EC)), or no-exercise control (CONT) until aged nine months. Depression-, anxiety-, and cognitive-like behaviours were tested with the forced swim test, open field and elevated zero maze, Y-maze, and Barnes maze. The expression of 75 hippocampal genes were investigated by high-throughput quantitative polymerase chain reaction (qPCR). RESULTS: Exercise cessation increased depression- and anxiety-like behaviours, and impaired spatial learning and cognitive flexibility compared to CONT and EXC mice. 10/75 hippocampal genes were differentially expressed in EC mice, including increased expression of neurogenesis associated genes (Ntrk1), and reduced expression of immune (Il10, Gfap) and monoamine related genes (Htr1a) compared to CONT mice. Altered expression of nine genes including increased Slc6a4 and reduced Sirt1 expression were shown in EC mice compared to EXC mice. CONCLUSIONS: Exercise cessation increased depression- and anxiety-like behaviours and impaired some cognition-like behaviours with altered neurogenic, monoaminergic, and immune hippocampal gene expression consistent with the pathogenesis of depression and related anxiety described by the neurogenic, monoaminergic, and immune hypotheses of depression. Mice and humans share mammalian physiology, so these findings could be relevant to humans. These results require replication and possibly translation into high-quality pilot clinical trials.

Neuroinflammation and cognition across psychiatric conditions.

Cognitive impairments reported across psychiatric conditions (ie, major depressive disorder, bipolar disorder, schizophrenia, and posttraumatic stress disorder) strongly impair the quality of life of patients and the recovery of those conditions. There is therefore a great need for consideration for cognitive dysfunction in the management of psychiatric disorders. The redundant pattern of cognitive impairments across such conditions suggests possible shared mechanisms potentially leading to their development. Here, we review for the first time the possible role of inflammation in cognitive dysfunctions across psychiatric disorders. Raised inflammatory processes (microglia activation and elevated cytokine levels) across diagnoses could therefore disrupt neurobiological mechanisms regulating cognition, including Hebbian and homeostatic plasticity, neurogenesis, neurotrophic factor, the HPA axis, and the kynurenine pathway. This redundant association between elevated inflammation and cognitive alterations across psychiatric disorders hence suggests that a cross-disorder approach using pharmacological and nonpharmacological (ie, physical activity and nutrition) anti-inflammatory/immunomodulatory strategies should be considered in the management of cognition in psychiatry.

Strengths and limitations of computer assisted telephone interviews (CATI) for nutrition data collection in rural Kenya.

Despite progress in fighting undernutrition, Africa has the highest rates of undernutrition globally, exacerbated by drought and conflict. Mobile phones are emerging as a tool for rapid, cost effective data collection at scale in Africa, as mobile phone subscriptions and phone ownership increase at the highest rates globally. To assess the feasibility and biases of collecting nutrition data via computer assisted telephone interviews (CATI) to mobile phones, we measured Minimum Dietary Diversity for Women (MDD-W) and Minimum Acceptable Diet for Infants and Young Children (MAD) using a one-week test-retest study on 1,821 households in Kenya. Accuracy and bias were assessed by comparing individual scores and population prevalence of undernutrition collected via CATI with data collected via traditional face-to-face (F2F) surveys. We were able to reach 75% (n = 1366) of study participants via CATI. Women's reported nutrition scores did not change with mode for MDD-W, but children's nutrition scores were significantly higher when measured via CATI for both the dietary diversity (mean increase of 0.45 food groups, 95% confidence interval 0.34-0.56) and meal frequency (mean increase of 0.75 meals per day, 95% confidence interval 0.53-0.96) components of MAD. This resulted in a 17% higher inferred prevalence of adequate diets for infants and young children via CATI. Women without mobile-phone access were younger and had fewer assets than women with access, but only marginally lower dietary diversity, resulting in a small non-coverage bias of 1-7% due to exclusion of participants without mobile phones. Thus, collecting nutrition data from rural women in Africa with mobile phones may result in 0% (no change) to as much as 25% higher nutrition estimates than collecting that information in face-to-face interviews.

TNF signalling via the TNF receptors mediates the effects of exercise on cognition-like behaviours.

BACKGROUND: Altered TNF levels are associated with cognitive impairment in depression, schizophrenia, bipolar disorder, and Alzheimer's disease (AD). Exercise improves cognition-like behaviours, reduces the expression of tumour necrosis factor alpha (TNF), and increases expression of the soluble TNF receptors soluble TNFR1 (sTNFR1) and sTNFR2. We suggest TNF and its receptors are involved in cognitive function and dysfunction, and investigate whether exercise mediates its effects on cognitive function via TNF and its receptors. METHODS: We utilised C57BL/6, TNF-/-, TNFR1-/-, and TNFR2-/- mice to compare exercise to non-exercise control groups to investigate whether exercise exerts its effects on various types of cognition-like behaviours via TNF and its receptors. RESULTS: Recognition memory improved with exercise in WT mice, was impaired in TNFR1-/- exercise mice, showed non-significant impairment with exercise in TNF-/- mice, and no changes in TNFR2-/- mice. In spatial learning there were exercise related improvements in WT mice, non-significant but meaningful impairments evident in TNFR1-/- exercise mice, modest improvement in TNF-/- exercise mice, and potentially meaningful non-significant improvements in TNFR2-/- exercise mice. Moreover, WT and TNFR2-/- mice displayed noteworthy non-significant improvements in spatial memory, whereas TNFR1-/- exercise mice demonstrated non-significant spatial memory impairment. Exercise did not alter cognitive flexibility in any strain. DISCUSSION: TNF receptor signalling via the TNFR1 and TNFR2 appears to mediate the effects of exercise on cognitive-like behaviours. The potential for exercise to regulate human TNF and TNF signalling and cognitive dysfunction needs investigation under inflammatory conditions including depression and neuropsychiatric disorders.

Exercise related anxiety-like behaviours are mediated by TNF receptor signaling, but not depression-like behaviours.

Depression can involve disrupted pro-inflammatory TNF signaling via the TNF receptors TNFR1 and TNFR2, or the soluble TNF receptors sTNFR1 and sTNFR2. However, exercise might attenuate pro-inflammatory signaling in depression and related anxiety. We hypothesized that six months voluntary wheel running exercise would improve depression-like and anxiety-like behaviours in WT and TNFR1-/- mice, but not in TNF-/- and TNFR2-/- mice compared to their respective control mice. METHODS: We investigated the effects of six months voluntary wheel running exercise on open field (OF) and elevated zero maze (EZM) anxiety-like behaviours, and forced swim test (FST) depression-like behaviours in control and exercise WT, TNF-/-, TNFR1-/-, and TNFR2-/- mice with two-way ANOVAs. RESULTS: Exercise reduced of anxiety-like behaviours in TNFR2-/- exercise mice compared to their respective controls. Compared to WT control mice, WT exercise mice displayed significantly reduced EZM anxiety-like behaviours. There were no exercise related changes in FST immobility time. Between-strains analyses found WT control and exercise mice displayed reduced EZM anxiety-like behaviours compared to TNF-/- and TNFR1-/- control and exercise mice, and WT exercise mice displayed reduced anxiety-like behavior compared to TNFR2-/- exercise mice. DISCUSSION: Exercise associated TNFR1 and TNFR2 signaling in concert in WT exercise mice mediated reductions in aspects of anxiety-like behaviours. These findings are consistent with the current view that imbalances in TNF signaling are involved in disrupted affect. Additional studies are needed to further explore the roles of exercise related TNFR1 and TNFR2 signaling in anxiety-like and depression-like behaviours.

The effects of aerobic exercise on depression-like, anxiety-like, and cognition-like behaviours over the healthy adult lifespan of C57BL/6 mice.

Preclinical studies have demonstrated exercise improves various types of behaviours such as anxiety-like, depression-like, and cognition-like behaviours. However, these findings were largely conducted in studies utilising short-term exercise protocols, and the effects of lifetime exercise on these behaviours remain unknown. This study investigates the behavioural effects of lifetime exercise in normal healthy ageing C57BL/6 mice over the adult lifespan. 12 week-old C57BL/6 mice were randomly assigned to voluntary wheel running or non-exercise (control) groups. Exercise commenced at aged 3 months and behaviours were assessed in young adult (Y), early middle age (M), and old (O) mice (n=11-17/group). The open field and elevated zero maze examined anxiety-like behaviours, depression-like behaviours were quantified with the forced swim test, and the Y maze and Barnes maze investigated cognition-like behaviours. The effects of lifetime exercise were not simply an extension of the effects of chronic exercise on anxiety-like, depression-like, and cognition-like behaviours. Exercise tended to reduce overt anxiety-like behaviours with ageing, and improved recognition memory and spatial learning in M mice as was expected. However, exercise also increased anxiety behaviours including greater freezing behaviour that extended spatial learning latencies in Y female mice in particular, while reduced distances travelled contributed to longer spatial memory and cognitive flexibility latencies in Y and O mice. Lifetime exercise may increase neurogenesis-associated anxiety. This could be an evolutionary conserved adaptation that nevertheless has adverse impacts on cognition-like function, with particularly pronounced effects in Y female mice with intact sex hormones. These issues require careful investigation in future rodent studies.