Inhibitory control mediates the association between body mass index and math performance in children: A cross-sectional study.

BACKGROUND: Overweight and obesity affect more than 18% of children and adolescents in the world. Obesity-related associations with brain morphology might be associated with reduced efficiency of inhibitory control. This association highlights a possible mechanism by which obesity impacts intelligence and academic achievement. Prior work indicates a mediating effect of inhibitory control on the relationship between body mass index (BMI) and intelligence and academic achievement. However, although obesity is associated with impaired math performance, we do not know whether inhibitory control also mediates the relationship between BMI and math performance. This study tests the hypothesis that inhibitory control statistically mediates the relationship between BMI and math performance. METHODS: 161 children (9 to 13 years old, 80 female) participated in the present study. We evaluated BMI; math performance, in a test composed of 20 arithmetic equations of the type x = (a × b) - c; and inhibitory control through the Flanker test. We carried out Spearman correlation tests, hierarchical multiple linear regression, and tested the confidence of the model where inhibitory control statistically mediates the indirect association between BMI and math performance. Mediation analysis in this cross-sectional study aimed to improve understanding of indirect relationships and offer insights into possible causal connections. RESULTS: Better math performance and lower BMI were associated with greater accuracy on the inhibitory control test and greater accuracy on the inhibitory control test was associated with better performance on math test. We found an indirect association between higher BMI in children and impairments in math performance, that was mediated by inhibitory control (a: -0.008, p = 0.025; b: 7.10, p = 0.0004; c: 0.05, p = 0.592; c': 0.11, p = 0.238; Indirect Effect: -0.0599, 95% CI: -0.13, -0.005). CONCLUSIONS: An indirect association between higher body mass indices in children and impairments in math performance was detected, through the impact that BMI has on inhibitory control.

Unexpected cognitive similarities between older adults and young people: Scores variability and cognitive performances.

BACKGROUND: Increased interindividual variability in cognitive performance during aging has been proposed as an indicator of cognitive reserve. OBJECTIVE: To determine if interindividual variability performance in episodic memory (PAL), working memory (SWM), reaction time (RTI), and sustained attention (RVP) could differentiate clusters of differential cognitive performance in healthy young and older adults and search for cognitive tests that most contribute to these differential performances. METHODS: We employed hierarchical cluster and canonical discriminant function analyses of cognitive scores using the Cambridge Neuropsychological Test Automated Battery (CANTAB) to identify cognitive variability in older and young adults using the coefficient of variability of cognitive performances between and within groups. We also analyzed potential influences of age, education, and physical activity. RESULTS: Cluster analysis distinguished groups with differential cognitive performance and correlation analysis revealed coefficient of variability and cognitive performance associations. The greater the coefficient of variability the poorer was cognitive performance in RTI but not in PAL and SWM. Older adults showed diverse trajectories of cognitive decline, and better education or higher percentage of physically active individuals exhibited better cognitive performance in both older and young adults. CONCLUSION: PAL and SWM are the most sensitive tests to investigate the wide age range encompassing older and young adults. In older adults' intragroup analysis PAL showed greater discriminatory capacity, indicating its potential for clinical applications late in life. Our data underscore the importance of studying variability as a tool for early detection of subtle cognitive declines and for interpreting results that deviate from normality.

Risk Polymorphisms of FNDC5, BDNF, and NTRK2 and Poor Education Interact and Aggravate Age-Related Cognitive Decline.

Cognitive abilities tend to decline with aging, with variation between individuals, and many studies seek to identify genetic biomarkers that more accurately anticipate risks related to pathological aging. We investigated the influence of BDNF, NTRK2, and FNDC5 single nucleotide polymorphisms (SNPs) on the cognitive performance of young and older adults with contrasting educational backgrounds. We addressed three questions: (1) Is education associated with reduced age-related cognitive decline? (2) Does the presence of SNPs explain the variation in cognitive performance observed late in life? (3) Is education differentially associated with cognition based on the presence of BDNF, NTRK2, or FNDC5 polymorphisms? We measured the cognitive functions of young and older participants, with lower and higher education, using specific and sensitive tests of the Cambridge Automated Neuropsychological Test Assessment Battery. A three-way ANOVA revealed that SNPs were associated with differential performances in executive functions, episodic memory, sustained attention, mental and motor response speed, and visual recognition memory and that higher educational levels improved the affected cognitive functions. The results revealed that distinct SNPs affect cognition late in life differentially, suggesting their utility as potential biomarkers and emphasizing the importance of cognitive stimulation that advanced education early in life provides.

Pilates and Cognitive Stimulation in Dual Task an Intervention Protocol to Improve Functional Abilities and Minimize the Rate of Age-Related Cognitive Decline in Postmenopausal Women.

It is already known the effectiveness of Pilates training on cognitive and functional abilities. It is also known that dual-task exercise and cognitive stimuli improve cognition and functional capacity. However, no previous report combined cognitive stimuli and Pilates in dual task and measured its effects on the cognitive and physical performances of postmenopausal women. OBJECTIVE: To apply an interventional dual-task (PILATES-COG) protocol and to evaluate its influence on memory, language, and functional physical performances on healthy, community-dwelling postmenopausal older women. METHODS: 47 women with amenorrhea for at least 12 months participated in this study. Those allocated on the PILATES-COG group underwent a 12-week, twice a week regimen of 50 min sessions of simultaneous mat Pilates exercise program and cognitive tasks. Cognitive and physical functional performance were assessed. Two-way mixed ANOVA was used for data analysis, and Bonferroni post hoc tests were used for within- and between-group comparisons. RESULTS: The PILATES-COG group showed significant improvement after the intervention in semantic verbal fluency (p < 0.001; ηρ² = 0.268), phonological verbal fluency (p < 0.019; ηρ² = 0.143), immediate memory (p < 0.001; ηρ² = 0.258), evocation memory (p < 0.001 ηρ² = 0.282), lower-limb muscle strength (p < 0.001; ηρ² = 0.447), balance (p < 0.001; ηρ² = 0.398), and dual-ask cost (p < 0.05; ηρ² = 0.111) assessments on healthy, community-dwelling postmenopausal older women. CONCLUSION: This is the first report of a feasible and effective approach using Pilates and cognitive stimulation in dual task for the reduction of age-related cognitive decline and the improvement of physical functional performance in healthy postmenopausal women.

Dual-Task Exercise to Improve Cognition and Functional Capacity of Healthy Older Adults.

BACKGROUND: It has been suggested that physical inactivity and lack of stimulating cognitive activity are the two most significant modifiable risk factors to impair cognitive function. Although many studies that investigated the cognitive effects of physical exercise and cognitive stimuli in dual-task conditions showed improved cognitive performance, others have not confirmed these findings. The main aim of the present work is to analyze the effects of a dual-task multimodal physical exercise training, at moderate intensity, and cognitive stimulation on cognitive and physical function in healthy older adults. METHODS: This clinical trial was registered on the Brazilian Registry of Clinical Trials (RBR-9zrx3d). Here we tested the effects of a dual-task multimodal physical exercise training, at moderate intensity, on cognitive and physical function and quality of life in community dwelling older adults. The training protocol included 24 group sessions, 2/week, per 75 min. Cognition was assessed using CANTAB automated neuropsychological tests and Functional Capacity to Exercise tests. Performance was compared from baseline to post intervention and to a non-exercise control group using Mixed Linear Model for repeated measures. RESULTS: Control (CG) and dual-task (DTEx) groups progressed differentially over time on performance of episodic memory, sustained visual attention, functional mobility, cardiorespiratory fitness, lower limbs strength resistance, agility, quality of life and dual-task performance with significant improved DTEx performance. Control group did not show any significant changes on these tests except for showing a reduction in dual-task performance. CONCLUSION: We suggest that the dual-task combination of multisensory cognitive stimulation and multimodal moderate physical exercise training, twice a week, may be adopted as an effective program to reduce progression of age-related cognitive decline and improve physical fitness and quality of life on healthy older adults. CLINICAL TRIAL REGISTRATION: Brazilian Registry of Clinical Trials: https://ensaiosclinicos.gov.br/rg/RBR-9zrx3d -UTN code: U1111-1233-6349.

Associations between cardiorespiratory fitness, physical activity, intraindividual variability in behavior, and cingulate cortex in younger adults.

BACKGROUND: Higher levels of cardiorespiratory fitness (CRF) and greater amounts of physical activity have been associated with lower intraindividual variability (IIV) in executive function in children and older adults. In the present study, we examined whether CRF, measured as maximal oxygen uptake (VO2max), and daily volume of moderate-to-vigorous intensity physical activity (MVPA) were associated with IIV of reaction time during performance of the incongruent condition of the Stroop task in younger adults. Further, we examined whether the thickness of the cingulate cortex was associated with regulating variability in reaction time performance in the context of CRF or physical activity. METHODS: CRF (measured as VO2max), accelerometry-measured MVPA, Stroop performance, and thickness of the rostral anterior cingulate cortex (rACC) derived from magnetic resonance imaging data were collected in 48 younger adults (age = 24.58 ± 4.95 years, mean ± SD). Multiple regression was used to test associations between IIV during the Stroop task and CRF, MVPA, and rACC thickness. Mediation was tested using maximum likelihood estimation with bootstrapping. RESULTS: Consistent with our predictions, higher VO2max was associated with greater rACC thickness for the right hemisphere and greater daily amounts of MVPA were associated with greater rACC thickness for both the left and right hemispheres. Greater thickness of the right rACC was associated with lower IIV for the incongruent condition of the Stroop task. CRF and MVPA were not directly associated with IIV. However, we did find that IIV and both CRF and MVPA were indirectly associated via the thickness of the right rACC. CONCLUSION: These results indicate that higher CRF and greater daily volume of MVPA may be associated with lower IIV during the Stroop task via structural integrity of the rACC. Randomized controlled trials of MVPA would provide crucial information about the causal relations between these variables.

Water-based exercise and resistance training improve cognition in older adults / Hidroginástica e treinamento resistido melhoram a cognição de idosos / Hidrogimnasia y entrenamiento resistido mejoran la cognición de personas de la tercera edad

ABSTRACT Introduction: Physical exercise has been associated with maintenance of physical abilities and the reduction of age-related cognitive decline, and is considered both a low-cost primary prevention strategy and a non-pharmacological treatment of cognitive dysfunction in older people. However, the contribution of each type of physical exercise to the cognitive health of the elderly population has not yet been fully investigated. Objective: This study investigated the possible influences of water-based and resistance training exercises on the cognitive performance of healthy older adults in automated tests, and investigated which test(s) would be the most effective indicator of differences in aging cognitive performance. Methods: Three groups of community-dwelling healthy older adults: water-based exercise group, resistance training group and sedentary group, were assessed using an automated set of neuropsychological tests (CANTAB) and tests to assess functional exercise capacity. Results were compared by one-way analysis of variance (ANOVA) and Pearson linear correlation. Results: The water-based exercise group had the best functional exercise capacity scores and the best performance in the reaction time evaluation (response and movement latencies). The resistance training group had less movement latency than the sedentary group. Functional mobility was positively correlated with response and movement latency. Conclusions: Taken together our findings show that physical exercise contributes to the preservation of cognitive function in healthy older adults and that water-based exercise has better results than resistance training in terms of reaction time. Moreover, the changes related to reaction time function were detected before the changes in working memory functions, sustained attention and learning in the sedentary participants, suggesting that this variable could be an early sensitive indicator of subtle cognitive changes associated with aging. Level of Evidence II; Retrospective study.

RESUMO Introdução: A prática de exercícios físicos tem sido associada à manutenção das habilidades físicas e redução do declínio cognitivo durante o envelhecimento, sendo considerada uma estratégia de prevenção primária de baixo custo, assim como tratamento não-farmacológico da disfunção cognitiva em idosos. Entretanto, a contribuição das diferentes modalidades de exercícios físicos sobre a saúde cognitiva da população idosa carece de investigação. Objetivo: O presente estudo investigou as possíveis influências da hidroginástica e musculação no desempenho cognitivo dos adultos idosos saudáveis em testes automatizados e qual(is) teste(s) seria o indicador mais sensível das diferenças de desempenho cognitivo. Métodos: Três grupos de idosos saudáveis, residentes na comunidade, praticantes de hidroginástica, musculação ou sedentários foram avaliados através de uma bateria automatizada de testes neuropsicológicos (CANTAB) e testes para avaliação da capacidade funcional ao exercício. Os resultados foram comparados através da análise de variância de 1 critério (ANOVA) e da correlação linear de Pearson. Resultados: O grupo de hidroginástica apresentou melhor capacidade funcional ao exercício e melhor desempenho na avaliação do tempo de reação (latências de resposta e de movimento). Os praticantes de musculação apresentaram menor latência de movimento do que os sedentários. A mobilidade funcional foi positivamente correlacionada às latências de resposta e de movimento. Conclusão: Considerados em conjunto, nossos resultados indicam que o exercício físico contribui para a preservação da função cognitiva em idosos saudáveis e que a hidroginástica apresenta melhores resultados do que a musculação em relação ao tempo de reação. Além disso, as mudanças relacionadas à função tempo de reação foram detectadas antes das mudanças nas funções de memória de trabalho, atenção sustentada e aprendizado nos participantes sedentários, sugerindo que essa variável pode ser um indicador sensível e precoce de sutis mudanças cognitivas associadas ao envelhecimento. Nível de Evidência II; Estudo retrospectivo.

RESUMEN Introducción: La práctica de ejercicios físicos ha sido asociada al mantenimiento de las habilidades físicas y reducción de la disminución cognitiva durante el envejecimiento, siendo considerada una estrategia de prevención primaria de bajo costo, así como tratamiento no farmacológico de la disfunción cognitiva en personas de la tercera edad. Entretanto, la contribución de las diferentes modalidades de ejercicios físicos sobre la salud cognitiva de la población de la tercera edad carece de investigación. Objetivo: El presente estudio investigó las posibles influencias de la hidrogimnasia y musculación en el desempeño cognitivo de los adultos de la tercera edad saludables en tests automatizados y qué test(s) sería el indicador más sensible de las diferencias de desempeño cognitivo. Métodos: Tres grupos de personas de la tercera edad saludables, residentes en la comunidad, practicantes de hidrogimnasia, musculación o sedentarios fueron evaluados a través de una batería automatizada de tests neuropsicológicos (CANTAB) y tests para evaluación de la capacidad funcional para el ejercicio. Los resultados fueron comparados a través del análisis de variancia de 1 criterio (ANOVA) y de la correlación lineal de Pearson. Resultados: El grupo de hidrogimnasia presentó mejor capacidad funcional para el ejercicio y mejor desempeño en la evaluación del tiempo de reacción (latencias de respuesta y de movimiento). Los practicantes de musculación presentaron menor latencia de movimiento que los sedentarios. La movilidad funcional fue positivamente correlacionada a las latencias de respuesta y de movimiento. Conclusión: Considerados en conjunto, nuestros resultados indican que el ejercicio físico contribuye para la preservación de la función cognitiva en personas de la tercera edad saludables y que la hidrogimnasia presenta mejores resultados que la musculación con relación al tiempo de reacción. Además, los cambios relacionados a la función tiempo de reacción fueron detectados antes que los cambios em las funciones de memoria de trabajo, atención sustentada y aprendizaje en los participantes sedentarios, sugiriendo que esa variable puede ser un indicador sensible y precoz de sutiles cambios cognitivos asociados al envejecimiento. Nivel de Evidencia II; Estudio retrospectivo.

Virus Infections on Prion Diseased Mice Exacerbate Inflammatory Microglial Response.

We investigated possible interaction between an arbovirus infection and the ME7 induced mice prion disease. C57BL/6, females, 6-week-old, were submitted to a bilateral intrahippocampal injection of ME7 prion strain (ME7) or normal brain homogenate (NBH). After injections, animals were organized into two groups: NBH (n = 26) and ME7 (n = 29). At 15th week after injections (wpi), animals were challenged intranasally with a suspension of Piry arbovirus 0.001% or with NBH. Behavioral changes in ME7 animals appeared in burrowing activity at 14 wpi. Hyperactivity on open field test, errors on rod bridge, and time reduction in inverted screen were detected at 15th, 19th, and 20th wpi respectively. Burrowing was more sensitive to earlier hippocampus dysfunction. However, Piry-infection did not significantly affect the already ongoing burrowing decline in the ME7-treated mice. After behavioral tests, brains were processed for IBA1, protease-resistant form of PrP, and Piry virus antigens. Although virus infection in isolation did not change the number of microglia in CA1, virus infection in prion diseased mice (at 17th wpi) induced changes in number and morphology of microglia in a laminar-dependent way. We suggest that virus infection exacerbates microglial inflammatory response to a greater degree in prion-infected mice, and this is not necessarily correlated with hippocampal-dependent behavioral deficits.

Age, environment, object recognition and morphological diversity of GFAP-immunolabeled astrocytes.

BACKGROUND: Few studies have explored the glial response to a standard environment and how the response may be associated with age-related cognitive decline in learning and memory. Here we investigated aging and environmental influences on hippocampal-dependent tasks and on the morphology of an unbiased selected population of astrocytes from the molecular layer of dentate gyrus, which is the main target of perforant pathway. RESULTS: Six and twenty-month-old female, albino Swiss mice were housed, from weaning, in a standard or enriched environment, including running wheels for exercise and tested for object recognition and contextual memories. Young adult and aged subjects, independent of environment, were able to distinguish familiar from novel objects. All experimental groups, except aged mice from standard environment, distinguish stationary from displaced objects. Young adult but not aged mice, independent of environment, were able to distinguish older from recent objects. Only young mice from an enriched environment were able to distinguish novel from familiar contexts. Unbiased selected astrocytes from the molecular layer of the dentate gyrus were reconstructed in three-dimensions and classified using hierarchical cluster analysis of bimodal or multimodal morphological features. We found two morphological phenotypes of astrocytes and we designated type I the astrocytes that exhibited significantly higher values of morphological complexity as compared with type II. Complexity = [Sum of the terminal orders + Number of terminals] × [Total branch length/Number of primary branches]. On average, type I morphological complexity seems to be much more sensitive to age and environmental influences than that of type II. Indeed, aging and environmental impoverishment interact and reduce the morphological complexity of type I astrocytes at a point that they could not be distinguished anymore from type II. CONCLUSIONS: We suggest these two types of astrocytes may have different physiological roles and that the detrimental effects of aging on memory in mice from a standard environment may be associated with a reduction of astrocytes morphological diversity.

Beneficial effects of multisensory and cognitive stimulation in institutionalized elderly: 12-months follow-up.

We previously demonstrated the beneficial effects of a multisensory and cognitive stimulation program, consisting of 48 sessions, twice a week, to improve the cognition of elderly subjects living either in long-term care institutions (institutionalized - I) or in communities with their families (noninstitutionalized - NI). In the present study, we evaluated these subjects after the end of the intervention and compared the rate of age-related cognitive decline of those living in an enriched community environment (NI group, n=15, 74.1±3.9 years old) with those living in the impoverished environment of long-term care institutions (I group, n=20, 75.1±6.8 years old). Both groups participated fully in our stimulation program. Over 1 year, we conducted revaluations at five time points (2 months, 4 months, 6 months, 8 months, and 12 months) after the completion of the intervention. Both elderly groups were evaluated with the mini-mental state examination and selected language tests. Progressive cognitive decline was observed in both groups over the period. Indeed, it took only 4-6 months after the end of the stimulation program for significant reductions in language test scores to become apparent. However, earlier reductions in test scores were mainly associated with I group, and linguistic prosody test scores were significantly affected by institutionalization and time, two variables that interacted and reduced these scores. Moreover, I group reduced the Montréal cognitive assessment battery language tests scores 4 months before NI group. It remains to be investigated what mechanisms may explain the earlier and more intense language losses in institutionalized elderly.

Three-dimensional morphometric analysis of microglial changes in a mouse model of virus encephalitis: age and environmental influences.

Many RNA virus CNS infections cause neurological disease. Because Piry virus has a limited human pathogenicity and exercise reduces activation of microglia in aged mice, possible influences of environment and aging on microglial morphology and behavior in mice sublethal encephalitis were investigated. Female albino Swiss mice were raised either in standard (S) or in enriched (EE) cages from age 2 to 6 months (young - Y), or from 2 to 16 months (aged - A). After behavioral tests, mice nostrils were instilled with Piry-virus-infected or with normal brain homogenates. Brain sections were immunolabeled for virus antigens or microglia at 8 days post-infection (dpi), when behavioral changes became apparent, and at 20 and 40 dpi, after additional behavioral testing. Young infected mice from standard (SYPy) and enriched (EYPy) groups showed similar transient impairment in burrowing activity and olfactory discrimination, whereas aged infected mice from both environments (EAPy, SAPy) showed permanent reduction in both tasks. The beneficial effects of an enriched environment were smaller in aged than in young mice. Six-hundred and forty microglial cells, 80 from each group were reconstructed. An unbiased, stereological sampling approach and multivariate statistical analysis were used to search for microglial morphological families. This procedure allowed distinguishing between microglial morphology of infected and control subjects. More severe virus-associated microglial changes were observed in young than in aged mice, and EYPy seem to recover microglial homeostatic morphology earlier than SYPy . Because Piry-virus encephalitis outcomes were more severe in aged mice, it is suggested that the reduced inflammatory response in those individuals may aggravate encephalitis outcomes.

CANTAB object recognition and language tests to detect aging cognitive decline: an exploratory comparative study.

OBJECTIVE: The recognition of the limits between normal and pathological aging is essential to start preventive actions. The aim of this paper is to compare the Cambridge Neuropsychological Test Automated Battery (CANTAB) and language tests to distinguish subtle differences in cognitive performances in two different age groups, namely young adults and elderly cognitively normal subjects. METHOD: We selected 29 young adults (29.9±1.06 years) and 31 older adults (74.1±1.15 years) matched by educational level (years of schooling). All subjects underwent a general assessment and a battery of neuropsychological tests, including the Mini Mental State Examination, visuospatial learning, and memory tasks from CANTAB and language tests. Cluster and discriminant analysis were applied to all neuropsychological test results to distinguish possible subgroups inside each age group. RESULTS: Significant differences in the performance of aged and young adults were detected in both language and visuospatial memory tests. Intragroup cluster and discriminant analysis revealed that CANTAB, as compared to language tests, was able to detect subtle but significant differences between the subjects. CONCLUSION: Based on these findings, we concluded that, as compared to language tests, large-scale application of automated visuospatial tests to assess learning and memory might increase our ability to discern the limits between normal and pathological aging.

Enriched environment and masticatory activity rehabilitation recover spatial memory decline in aged mice.

BACKGROUND: To measure the impact of masticatory reduction on learning and memory, previous studies have produced experimental masticatory reduction by modified diet or molar removal. Here we induced spatial learning impairment in mice by reducing masticatory activity and then tested the effect of a combination of environmental enrichment and masticatory rehabilitation in recovering spatial learning at adulthood and in later life. For 6 months (6M) or 18 months (18M), we fed three groups of mice from postnatal day 21 respectively with a hard diet (HD) of pellets; pellets followed by a powdered, soft diet (HD/SD, divided into equal periods); or pellets followed by powder, followed by pellets again (HD/SD/HD, divided into equal periods). To mimic sedentary or active lifestyles, half of the animals from each group were raised from weaning in standard cages (impoverished environment; IE) and the other half in enriched cages (enriched environment; EE). To evaluate spatial learning, we used the Morris water maze. RESULTS: IE6M-HD/SD mice showed lower learning rates compared with control (IE6M-HD) or masticatory rehabilitated (IE6MHD/SD/HD) animals. Similarly, EE-HD/SD mice independent of age showed lower performance than controls (EE-HD) or rehabilitated mice (EE-HD/SD/HD). However, combined rehabilitation and EE in aged mice improved learning rate up to control levels. Learning rates did not correlate with swim speed. CONCLUSIONS: Reduction in masticatory activity imposed on mice previously fed a hard diet (HD/SD) impaired spatial learning in the Morris water maze. In adults, masticatory rehabilitation recovered spatial abilities in both sedentary and active mice, and rehabilitation of masticatory activity combined with EE recovered these losses in aged mice.

Spatial memory decline after masticatory deprivation and aging is associated with altered laminar distribution of CA1 astrocytes.

BACKGROUND: Chewing imbalances are associated with neurodegeneration and are risk factors for senile dementia in humans and memory deficits in experimental animals. We investigated the impact of long-term reduced mastication on spatial memory in young, mature and aged female albino Swiss mice by stereological analysis of the laminar distribution of CA1 astrocytes. A soft diet (SD) was used to reduce mastication in the experimental group, whereas the control group was fed a hard diet (HD). Assays were performed in 3-, 6- and 18-month-old SD and HD mice. RESULTS: Eating a SD variably affected the number of astrocytes in the CA1 hippocampal field, and SD mice performed worse on water maze memory tests than HD mice. Three-month-old mice in both groups could remember/find a hidden platform in the water maze. However, 6-month-old SD mice, but not HD mice, exhibited significant spatial memory dysfunction. Both SD and HD 18-month-old mice showed spatial memory decline. Older SD mice had astrocyte hyperplasia in the strata pyramidale and oriens compared to 6-month-old mice. Aging induced astrocyte hypoplasia at 18 months in the lacunosum-moleculare layer of HD mice. CONCLUSIONS: Taken together, these results suggest that the impaired spatial learning and memory induced by masticatory deprivation and aging may be associated with altered astrocyte laminar distribution and number in the CA1 hippocampal field. The underlying molecular mechanisms are unknown and merit further investigation.

Early behavioral changes and quantitative analysis of neuropathological features in murine prion disease: stereological analysis in the albino Swiss mice model.

Behavioral and neuropathological changes have been widely investigated in murine prion disease but stereological based unbiased estimates of key neuropathological features have not been carried out. After injections of ME7 infected (ME7) or normal brain homogenates (NBH) into dorsal CA1 of albino Swiss mice and C57BL6, we assessed behavioral changes on hippocampal-dependent tasks. We also estimated by optical fractionator at 15 and 18 weeks post-injections (w.p.i.) the total number of neurons, reactive astrocytes, activated microglia and perineuronal nets (PN) in the polymorphic layer of dentate gyrus (PolDG), CA1 and septum in albino Swiss mice. On average, early behavioral changes in albino Swiss mice start four weeks later than in C57BL6. Cluster and discriminant analysis of behavioral data in albino Swiss mice revealed that four of nine subjects start to change their behavior at 12 w.p.i. and reach terminal stage at 22 w.p.i and the remaining subjects start at 22 w.p.i. and reach terminal stage at 26 w.p.i. Biotinylated dextran-amine BDA-tracer experiments in mossy fiber pathway confirmed axonal degeneration, and stereological data showed that early astrocytosis, microgliosis and reduction in the perineuronal nets are independent of a change in the number of neuronal cell bodies. Statistical analysis revealed that the septal region had greater levels of neuroinflammation and extracellular matrix damage than CA1. This stereological and multivariate analysis at early stages of disease in an outbred model of prion disease provided new insights connecting behavioral changes and neuroinflammation and seems to be important to understand the mechanisms of prion disease progression.

Influence of enriched environment on viral encephalitis outcomes: behavioral and neuropathological changes in albino Swiss mice.

An enriched environment has previously been described as enhancing natural killer cell activity of recognizing and killing virally infected cells. However, the effects of environmental enrichment on behavioral changes in relation to virus clearance and the neuropathology of encephalitis have not been studied in detail. We tested the hypothesis that environmental enrichment leads to less CNS neuroinvasion and/or more rapid viral clearance in association with T cells without neuronal damage. Stereology-based estimates of activated microglia perineuronal nets and neurons in CA3 were correlated with behavioral changes in the Piry rhabdovirus model of encephalitis in the albino Swiss mouse. Two-month-old female mice maintained in impoverished (IE) or enriched environments (EE) for 3 months were behaviorally tested. After the tests, an equal volume of Piry virus (IEPy, EEPy)-infected or normal brain homogenates were nasally instilled. Eight days post-instillation (dpi), when behavioral changes became apparent, brains were fixed and processed to detect viral antigens, activated microglia, perineuronal nets, and T lymphocytes by immuno- or histochemical reactions. At 20 or 40 dpi, the remaining animals were behaviorally tested and processed for the same markers. In IEPy mice, burrowing activity decreased and recovered earlier (8-10 dpi) than open field (20-40 dpi) but remained unaltered in the EEPy group. EEPy mice presented higher T-cell infiltration, less CNS cell infection by the virus and/or faster virus clearance, less microgliosis, and less damage to the extracellular matrix than IEPy. In both EEPy and IEPy animals, CA3 neuronal number remained unaltered. The results suggest that an enriched environment promotes a more effective immune response to clear CNS virus and not at the cost of CNS damage.