Unraveling the Influence of Litter Size, Maternal Care, Exercise, and Aging on Neurobehavioral Plasticity and Dentate Gyrus Microglia Dynamics in Male Rats.

This study explores the multifaceted influence of litter size, maternal care, exercise, and aging on rats' neurobehavioral plasticity and dentate gyrus microglia dynamics. Body weight evolution revealed a progressive increase until maturity, followed by a decline during aging, with larger litters exhibiting lower weights initially. Notably, exercised rats from smaller litters displayed higher body weights during the mature and aged stages. The dentate gyrus volumes showed no significant differences among groups, except for aged sedentary rats from smaller litters, which exhibited a reduction. Maternal care varied significantly based on litter size, with large litter dams showing lower frequencies of caregiving behaviors. Behavioral assays highlighted the detrimental impact of a sedentary lifestyle and reduced maternal care/large litters on spatial memory, mitigated by exercise in aged rats from smaller litters. The microglial dynamics in the layers of dentate gyrus revealed age-related changes modulated by litter size and exercise. Exercise interventions mitigated microgliosis associated with aging, particularly in aged rats. These findings underscore the complex interplay between early-life experiences, exercise, microglial dynamics, and neurobehavioral outcomes during aging.

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.

Unwanted Exacerbation of the Immune Response in Neurodegenerative Disease: A Time to Review the Impact.

The COVID-19 pandemic imposed a series of behavioral changes that resulted in increased social isolation and a more sedentary life for many across all age groups, but, above all, for the elderly population who are the most vulnerable to infections and chronic neurodegenerative diseases. Systemic inflammatory responses are known to accelerate neurodegenerative disease progression, which leads to permanent damage, loss of brain function, and the loss of autonomy for many aged people. During the COVID-19 pandemic, a spectrum of inflammatory responses was generated in affected individuals, and it is expected that the elderly patients with chronic neurodegenerative diseases who survived SARSCoV-2 infection, it will be found, sooner or later, that there is a worsening of their neurodegenerative conditions. Using mouse prion disease as a model for chronic neurodegeneration, we review the effects of social isolation, sedentary living, and viral infection on the disease progression with a focus on sickness behavior and on the responses of microglia and astrocytes. Focusing on aging, we discuss the cellular and molecular mechanisms related to immunosenescence in chronic neurodegenerative diseases and how infections may accelerate their progression.

Microglial Morphology Across Distantly Related Species: Phylogenetic, Environmental and Age Influences on Microglia Reactivity and Surveillance States.

Microglial immunosurveillance of the brain parenchyma to detect local perturbations in homeostasis, in all species, results in the adoption of a spectrum of morphological changes that reflect functional adaptations. Here, we review the contribution of these changes in microglia morphology in distantly related species, in homeostatic and non-homeostatic conditions, with three principal goals (1): to review the phylogenetic influences on the morphological diversity of microglia during homeostasis (2); to explore the impact of homeostatic perturbations (Dengue virus challenge) in distantly related species (Mus musculus and Callithrix penicillata) as a proxy for the differential immune response in small and large brains; and (3) to examine the influences of environmental enrichment and aging on the plasticity of the microglial morphological response following an immunological challenge (neurotropic arbovirus infection). Our findings reveal that the differences in microglia morphology across distantly related species under homeostatic condition cannot be attributed to the phylogenetic origin of the species. However, large and small brains, under similar non-homeostatic conditions, display differential microglial morphological responses, and we argue that age and environment interact to affect the microglia morphology after an immunological challenge; in particular, mice living in an enriched environment exhibit a more efficient immune response to the virus resulting in earlier removal of the virus and earlier return to the homeostatic morphological phenotype of microglia than it is observed in sedentary mice.

Contrasting migratory journeys and changes in hippocampal astrocyte morphology in shorebirds.

Semipalmated sandpiper (Calidris pusilla) migration to the Southern Hemisphere includes a 5-day non-stop flight over the Atlantic Ocean, whereas semipalmated plover (Charadrius semipalmatus) migration, to the same area, is largely over land, with stopovers for feeding and rest. We compared the number and 3D morphology of hippocampal astrocytes of Ch. semipalmatus before and after autumnal migration with those of C. pusilla to test the hypothesis that the contrasting migratory flights of these species could differentially shape hippocampal astrocyte number and morphology. We captured individuals from both species in the Bay of Fundy (Canada) and in the coastal region of Bragança (Brazil) and processed their brains for selective GFAP immunolabeling of astrocytes. Hierarchical cluster analysis of astrocyte morphological features distinguished two families of morphological phenotypes, named type I and type II, which were differentially affected after migratory flights. Stereological counts of hippocampal astrocytes demonstrated that the number of astrocytes decreased significantly in C. pusilla, but did not change in Ch. semipalmatus. In addition, C. pusilla and Ch. semipalmatus hippocampal astrocyte morphological features were differentially affected after autumnal migration. We evaluated whether astrocyte morphometric variables were influenced by phylogenetic differences between C. pusilla and Ch. semipalmatus, using phylogenetically independent contrast approach, and phylogenetic trees generated by nuclear and mitochondrial markers. Our findings suggest that phylogenetic differences do not explain the results and that contrasting long-distance migratory flights shape plasticity of type I and type II astrocytes in different ways, which may imply distinct physiological roles for these cells.

BALB/c female subjected to valproic acid during gestational period exhibited greater microglial and behavioral changes than male mice: A significant contra intuitive result.

Most animal model studies of autism spectrum disorders (ASD) were performed in males. Thus, little is known about the mechanisms underlying disease progression in females. Here, we searched for potential influences of sex and environment on gestational valproic acid-induced behavioral abnormalities using hippocampal-dependent tasks, and on number and morphometry of microglia of the molecular layer of the dentate gyrus (Mol-DG). We compared male and females BALB/c control mice with BALB/c mice gestationally exposed to VPA with regards to exploratory activity and risk assessment in novel environments. Pregnant females and males on gestational day 12.5 received VPA in saline (600 mg/kg body weight) or an equal volume of saline by gavage. After weaning, female and male offspring were housed separately either in standard laboratory cages (SE) or enriched cages (EE). At 5 months of age, these mice underwent behavioral testing and had their brains processed for microglia IBA1 immunolabeling. Compared with control mice, VPA-exposed mice exhibited abnormal behavior in exploring novel environments and assessing risk, and these effects were significantly greater in females than in males and less intense among mice from enriched cages. Three-way ANOVA revealed that environment, sex and valproic acid conditions interacted and altered the behavior results. Microglia number and volume of the Mol-DG were significantly higher in VPA-exposed groups raised in standard cages. The results of counting the intersects of microglia branching on Sholl's circles analyzed with permutational MANOVA, demonstrated that in comparison with males, there was a greater reduction in the number of intersections in females raised in standard cages. These findings suggest that the increased microglia and morphological changes might be associated with behavioral dysfunction in ASD. Moreover, the somatomotor and cognitive stimulation of environmental enrichment started at weaning may be beneficial for reducing behavioral abnormalities and reduction of microglia response in adulthood.

Long-term environmental enrichment reduces microglia morphological diversity of the molecular layer of dentate gyrus.

We investigated long-term environmental influences on morphology of microglia from the outer and middle thirds of molecular layer of the dentate gyrus (MolDG), and on microglia from dorsal and ventral dentate gyrus molecular layer. We also estimated the total number of MolDG microglia using stereology. For this purpose, microglia of the molecular layer of the dentate gyrus of 20-month-old female Swiss albino mice, housed from 21st postnatal day onwards, in the impoverished environment of the standard laboratory cages (SEA), or in a cage with an enriched environment (EEA), were reconstructed microscopically in three dimensions and compared with each other and with microglia of 6-month-old female Swiss albino mice, also housed from weaning onwards in an enriched cage (EEY). All mice had their brains sectioned and processed for immunolabeling for IBA-1, a selective microglia marker. Random and systematic microglia samples were reconstructed in three dimensions and classified morphologically using hierarchical cluster analysis, followed by discriminant function analysis. SEA and EEY showed two morphological phenotypes of microglia in both the outer and middle thirds of MolDG. EEA mice showed such a reduction in the morphological diversity of microglia that essentially a single morphotype was found. EEA mouse microglia showed an intermediate morphological complexity between types I and II SE microglia. We suggest that type I and type II microglia in SE mice may have different physiological roles and that long-term EE may be associated with adaptive responses of microglial phenotypes to somatomotor and cognitive stimuli.

Limbic Encephalitis Brain Damage Induced by Cocal Virus in Adult Mice Is Reduced by Environmental Enrichment: Neuropathological and Behavioral Studies.

We previously demonstrated, using the Piry virus model, that environmental enrichment promotes higher T-cell infiltration, fewer microglial changes, and faster central nervous system (CNS) virus clearance in adult mice. However, little is known about disease progression, behavioral changes, CNS cytokine concentration, and neuropathology in limbic encephalitis in experimental models. Using Cocal virus, we infected C57Bl6 adult mice and studied the neuroanatomical distribution of viral antigens in correlation with the microglial morphological response, measured the CNS cytokine concentration, and assessed behavioral changes. C57Bl6 adult mice were maintained in an impoverished environment (IE) or enriched environment (EE) for four months and then subjected to the open field test. Afterwards, an equal volume of normal or virus-infected brain homogenate was nasally instilled. The brains were processed to detect viral antigens and microglial morphological changes using selective immunolabeling. We demonstrated earlier significant weight loss and higher mortality in IE mice. Additionally, behavioral analysis revealed a significant influence of the environment on locomotor and exploratory activity that was associated with less neuroinvasion and a reduced microglial response. Thus, environmental enrichment was associated with a more effective immune response in a mouse model of limbic encephalitis, allowing faster viral clearance/decreased viral dissemination, reduced disease progression, and less CNS damage.

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.

Age and Environment Influences on Mouse Prion Disease Progression: Behavioral Changes and Morphometry and Stereology of Hippocampal Astrocytes.

Because enriched environment (EE) and exercise increase and aging decreases immune response, we hypothesized that environmental enrichment and aging will, respectively, delay and increase prion disease progression. Mice dorsal striatum received bilateral stereotaxic intracerebral injections of normal or ME7 prion infected mouse brain homogenates. After behavior analysis, animals were euthanized and their brains processed for astrocyte GFAP immunolabeling. Our analysis related to the environmental influence are limited to young adult mice, whereas age influence refers to aged mice raised on standard cages. Burrowing activity began to reduce in ME7-SE two weeks before ME7-EE, while no changes were apparent in ME7 aged mice (ME7-A). Object placement recognition was impaired in ME7-SE, NBH-A, and ME7-A but normal in all other groups. Object identity recognition was impaired in ME7-A. Cluster analysis revealed two morphological families of astrocytes in NBH-SE animals, three in NBH-A and ME7-A, and four in NBH-EE, ME7-SE, and ME7-EE. As compared with control groups, astrocytes from DG and CA3 prion-diseased animals show significant numerical and morphological differences and environmental enrichment did not reverse these changes but induced different morphological changes in GFAP+ hippocampal astroglia. We suggest that environmental enrichment and aging delayed hippocampal-dependent behavioral and neuropathological signs of disease progression.

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.

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.

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.

In vitro cytokines profile and ultrastructural changes of microglia and macrophages following interaction with Leishmania.

In the present study, we assessed morphological changes and cytokine production after in vitro interaction with causative agents of American cutaneous leishmaniasis and compared the microglia and macrophage immune responses. Cultures of microglia and macrophages infected with stationary-phase promastigotes of Leishmania (Viannia) shawi, Leishmania (Viannia) braziliensis or Leishmania (Leishmania) amazonensis were evaluated 24, 48 and 72 h after interaction. Macrophages only presented the classical phagocytic process while microglia also displayed large cytoplasmic projections similar to the ruffles described in macropinocytosis. In the macrophage cultures, the percentage of infected cells increased over time, in a fashion that was dependent on the parasite species. In contrast, in microglial cells as the culture time progressed, there was a significant reduction in the percentage of infected cells independent of parasite species. Measurements of cytokines in macrophage cultures 48 h after interactions revealed distinct expression patterns for different parasites, whereas in microglial cultures they were similar for all Leishmania tested species. Taken together, our results suggest that microglia may have a higher phagocytic ability and cytotoxic potential than macrophages for all investigated species. The robust response of microglia against all parasite species may suggest microglia have an important role in the defence against cerebral leishmaniasis.

Beneficial effects of multisensory and cognitive stimulation on age-related cognitive decline in long-term-care institutions.

The aim of the present report was to evaluate the effectiveness and impact of multisensory and cognitive stimulation on improving cognition in elderly persons living in long-term-care institutions (institutionalized [I]) or in communities with their families (noninstitutionalized [NI]). We compared neuropsychological performance using language and Mini-Mental State Examination (MMSE) test scores before and after 24 and 48 stimulation sessions. The two groups were matched by age and years of schooling. Small groups of ten or fewer volunteers underwent the stimulation program, twice a week, over 6 months (48 sessions in total). Sessions were based on language and memory exercises, as well as visual, olfactory, auditory, and ludic stimulation, including music, singing, and dance. Both groups were assessed at the beginning (before stimulation), in the middle (after 24 sessions), and at the end (after 48 sessions) of the stimulation program. Although the NI group showed higher performance in all tasks in all time windows compared with I subjects, both groups improved their performance after stimulation. In addition, the improvement was significantly higher in the I group than the NI group. Language tests seem to be more efficient than the MMSE to detect early changes in cognitive status. The results suggest the impoverished environment of long-term-care institutions may contribute to lower cognitive scores before stimulation and the higher improvement rate of this group after stimulation. In conclusion, language tests should be routinely adopted in the neuropsychological assessment of elderly subjects, and long-term-care institutions need to include regular sensorimotor, social, and cognitive stimulation as a public health policy for elderly persons.

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.

Dopaminergic cell populations of the rat substantia nigra are differentially affected by essential fatty acid dietary restriction over two generations.

Essential fatty acids play a crucial role in the activity of several neurotransmission systems, especially in the monoaminergic systems involved in cognitive and motor aspects of behavior. The present study investigated whether essential fatty acid dietary restriction over two generations could differentially affect dopaminergic cell populations located in the substantia nigra rostro-dorso-medial (SNrm) or caudo-ventro-lateral (SNcv) regions which display distinct neurochemical profile and vulnerability to lesions under selected pathological conditions. Wistar rats were raised from conception on control or experimental diets containing adequate or reduced levels of linoleic and α-linolenic fatty acids, respectively. Stereological methods were used to estimate both the number and soma size of tyrosine hydroxylase (TH)-immunoreactive neurons in the SNrm and SNcv. TH protein levels were assessed with Western blots. Long-term treatment with the experimental diet modified the fatty acid profile of midbrain phospholipids and significantly decreased TH protein levels in the ventral midbrain (3 fold), the number of TH-positive cells in the SNrm (∼20%) and the soma size of these neurons in both SNrm (∼20%) and SNcv (∼10%). The results demonstrate for the first time a differential sensitivity of two substantia nigra dopaminergic cell populations to unbalanced levels of essential fatty acids, indicating a higher vulnerability of SNrm to the harmful effects induced by docosahexaenoic acid brain deficiency.

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.