Teses em Neurociências e Biologia Celular (Doutorado) - PPGNBC/ICB

URI Permanente para esta coleçãohttps://repositorio.ufpa.br/handle/2011/2390

O Doutorado Acadêmico pertence ao Programa de Pós-Graduação em Neurociências e Biologia Celular (PPGNBC) do Instituto de Ciências Biológicas (ICB) da Universidade Federal do Pará (UFPA).

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Alteração diferencial nos astrócitos radiais do hipocampo e neurogênese em aves marinhas com rotas migratórias constantes
(Universidade Federal do Pará, 2019-08-17) LIMA, Camila Mendes de; MAGALHÃES, Nara Gyzely de Morais; http://lattes.cnpq.br/2519507561210918; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286; https://orcid.org/0000-0001-6611-6880
Little is known about environmental influences on radial glia–like α cells (radial astrocytes) and their relation to neurogenesis. Because radial glia is involved in adult neurogenesis and astrogenesis, we investigated this association in two migratory shorebird species that complete their autumnal migration using contrasting strategies. Before their flights to South America, the birds stop over at the Bay of Fundy in Canada. From there, the semipalmated sandpiper (Calidris pusilla) crosses the Atlantic Ocean in a non-stop 5-day flight, whereas the semipalmated plover (Charadrius semipalmatus) flies primarily overland with stopovers for rest and feeding. Using hierarchical cluster and discriminant analysis of morphometric features to classify three-dimensionally (3D) reconstructed cells, we identified two morphotypes of radial glia, designated as Type I and Type II. The migratory process affected these cells differentially, with more intense morphological changes in Type I than in Type II morphotypes in both species. We also compared the number of doublecortin (DCX)-immunolabeled neurons with morphometric features of radial glial–like α cells in the hippocampal V region between C. pusilla and C. semipalmatus before and after autumn migration. Compared with migrating birds, the convex hull surface of radial glial–like α cells of wintering birds significantly increased in both C. semipalmatus and C. pusilla. This increase correlated with an increase of the total number of DCX-immunolabeled neurons in wintering birds. The decreased radial astrocyte morphological complexity in the semipalmated sandpiper and its increase in the semipalmated plover, a species that probably relies more on visuospatial information for navigation, may be significant, despite phylogenetic and other differences between these taxa. The migratory flight of the semipalmated plover, with stopovers for feeding and rest, versus the non-stop flight of the semipalmated sandpiper may differentially affect radial astrocyte morphology and neurogenesis.
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Alterações da formação hipocampal do Calidris pusilla associadas à migração outonal de longa distância
(Universidade Federal do Pará, 2017-08-31) MAGALHÃES, Nara Gyzely de Morais; DINIZ, Cristovam Guerreiro; http://lattes.cnpq.br/1025250990755299; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
After breeding in the upper Arctic tundra, shorebirds affected by migratory restlessness trace an inherited preliminary route and use compasses, maps and visual landmarks, until they reach, in the northern hemisphere, stopover sites that have the necessary nutritional resources for fast and high gain of energy reserves for migratory journey, as in the Bay of Fundy-Canada. Following this stopover site that is used by 75% of the population of Calidris pusilla, the long-distance autumn migratory experience continues with uninterrupted 6-day non-stop flights over the Atlantic until these birds reach South America and then the island of Canela-Brazil. To test the hypothesis that the long-distance migratory process would influence neurogenesis, astrogenesis and activation of earlier-expression genes, we captured 12 individuals in full migratory activity in the Bay of Fundy and 9 individuals in the Island of Canela in Brazil. After selective immunostaining for mature neurons (NeuN), immature neurons (Dcx), astrocytes (GFAP), and neuronal activation by early genes (c-Fos), we quantified these markers in the hippocampal formation and compared the results of this quantification of the individuals in migration (Bay of Fundy) with those of wintering birds (Canela Island). We used quantitative stereological analyzes to estimate the total number of cells of hippocampal formation, number of active cells, total number of astrocytes and young and mature neurons. To verify if the differences found were statistically significant, we used the Student t test. Our results confirmed that autumnal migration alone, caused hippocampal changes in Calidris pusilla. After migration, we detected that the hippocampal formation has fewer activated cells and fewer astrocytes, more new neurons and greater relative volume in the quantified hemisphere (left hemisphere). However, this process did not influence the number of total cells and mature neurons. We suggest that the difference found between the volume and number of new neurons, of the full migration and wintering individuals, possibly occurred due to the migratory process in combination with local conditions found during the beginning of the wintering period. Taken together our findings demonstrate long-distance migratory shorebirds offer a unique opportunity to investigate many issues related to the cellular neurobiology of migration in general, and, on the neural plasticity associated with hippocampal neuronal and neurogenesis in adult birds.
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Em direção à costa brasileira fugindo do inverno: rotas migratórias contrastantes e plasticidade diferencial dos astrócitos hipocampais
(Universidade Federal do Pará, 2018-01-04) OLIVEIRA, Marcus Augusto de; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
One of the largest seasonal events on the planet is the migration of birds from the Arctic to the southern hemisphere fleeing from winter and returning to the Arctic during the spring to the breeding season. Billions of individuals need to remember the routes learned during this epic journey and find the same places to rest and feeding. These birds can navigate thousands of miles with great accuracy, utilizing their spatial and temporal memories associated with the hippocampus, a key area for accomplishing this task. Recently, we have shown that the semipalmated sandpiper Calidris pusilla, after crossing the Atlantic towards the coast of South America, revealed significant changes in its hippocampal astrocytes. In fact, the hippocampal astrocytes of birds captured on the coast of Bragança in Brazil, compared with those of the hippocampus of individuals caught in the Bay of Fundy, Canada, were less numerous and exhibited shrunken branches. In the present work, we used another semipalmated shorebird, Charadrius semipalmatus, which, although having the same start and end points of C. pusilla migration, uses a different migratory strategy, performing a flight over the continent with stops for rest and feeding. Taking advantage of the opportunity offered by contrasting migratory flights, we tested the hypothesis that wintering bird species of the C. semipalmatus caught on the coast of Bragança (Brazil) would show greater morphological complexities than the hippocampal astrocytes of these migratory birds captured in the Bay of Fundy (Canada). Since the stands for food and rest, as well as the constant change in the landscape would constitute an enriched environment of multisensory stimuli, we expected to find in the individuals of C. semipalmatus captured in Bragança, an increase of the complexity, in opposition to the reduction in complexity previously found in C. pusilla. To test this hypothesis, we compared the three-dimensional (3-D) morphological characteristics of the adult C. semipalmatus astrocytes captured in the Bay of Fundy (n = 265 cells) with those of wintering birds captured in the coastal region of Bragança, Brazil, (n = 242 cells), and compared with the results obtained with C. pusilla. The Neurolucida program was used for three-dimensional reconstructions and the hierarchical cluster analysis (Ward’s method) was used to classify cells. This analysis showed two families of astrocytes, which we designated Type I and Type II, based on several morphological characteristics. Contrary to our expectations, Type I and Type II phenotypes showed, on average, independently of the species, lower morphological complexity after migration, and this reduction was significantly higher in Type I than in Type II. The magnitudes of these changes were significantly higher in C. pusilla than in C. semipalmatus. Taken together, these findings suggest that contrasting long-distance migratory flight strategies may differentially affect the astrocyte morphology and that distinct astrocyte morphologies may be associated with different functional roles during migration.
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Enriquecimento ambiental reduz as alterações astrocitárias e a progressão da doença prion em modelo murino: ensaios morfométricos, estereológicos e comportamentais
(Universidade Federal do Pará, 2014-11-26) TORRES NETO, João Bento; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
It is well established that a sedentary lifestyle is a risk factor for a number of chronic diseases, including Alzheimer's disease. The neuropathology of Alzheimer's disease is characterized by amyloid deposits, neuronal loss, reactive gliosis, and vacuolization of the neuropil. Prion disease has been widely used as an experimental model for studying cellular and molecular aspects of chronic neurodegeneration much similar to that described in Alzheimer's disease. The impoverished environment of standard laboratory cages have been used to mimic a sedentary life whereas enriched environment has been used to mimic an active lifestyle. To test the hypothesis that an enriched environment can help to slow down the time course of chronic neurodegeneration associated with prion disease we induced prion disease in twenty Swiss albino female mice which had been housed at six months of age in an enriched environment (EE) or in a standard (SE) environment for five months. After this period bilateral stereotactic intracerebral injection of normal (NBH, n = 10) or infected brain homogenate (ME7, n = 10) were done. Infected brain homogenate was obtained from mice with clinical signs of terminal prion disease. The injected animals returned to their cages and housing conditions and grouped as follow: SE = NBH 5, EE = NBH 5, ME7 SE = 5, ME7 EE = 5. After three weeks post-injections the burrowing test was initiated. Burrowing is a sensitive task to hippocampal damage. 18 weeks after inoculation memory tests of object recognition was carried out. After behavioral tests animals were euthanized and their brains were histologically processed targeting astrocytic immunostaining of areas of interest. The progressive reduction of the activity of burrowing began in the thirteenth week after injection in group ME7 SE but only in the fifteenth week in ME7 EE group. The ability to recognize the displaced object in spatial memory test was impaired in ME7 SE group but remained normal in the other experimental groups. The test of discrimination between the new object and the family revealed no abnormalities. Quantitative analysis of GFAP immunostained cells were performed in the dorsal stratum radiatum of CA3 and in the polymorphic layer of the dorsal dentate gyrus. The stereological estimates of the total number of astrocytes and the volume of the cell body revealed that the number of astrocytes did not change but a significant hypertrophy occurs in CA3 cell bodies of ME7 SE and ME7 EE groups as compared to their respective controls. The average volume of the cell bodies of the ME7 EE group was smaller than that of the group ME7 SE. However similar analysis applied to the polymorphic layer revealed a significant increase in the number of astrocytes in the ME7 SE group in relation to NBH SE group and in ME7 EE compared to NBH EE. The volume of the cell body was also significantly higher in ME7 groups compared to their respective control groups. The three-dimensional morphometric analysis revealed significant increase in volume and surface area of the segments of astrocytic trees in diseased groups compared to controls. Environmental enrichment reduced swelling observed in the branches of ME7 group and increased the number of intersections of the distal branches in NBH EE group relative to NBH SE and the proximal branches in the group ME7 EE compared with ME7 SE. The use of cluster analysis and discriminant allowed the identification of morphometric parameters that contributed most to the distinction between the groups. To test the hypothesis that there are subfamilies of morphologically distinct astrocytes within each experimental group, we applied cluster and discriminant analysis to each experimental group and these analysis resulted in the formation of two distinct families in NBH SE group, three families in NBH EE and ME7 EE groups and four families in the ME7 SE group. The molecular and cellular changes, which lead to the formation of new families of astrocytes, and to the neuroprotection associated with an enriched environment slowing down the progression of the prion disease, remain to be investigated.
Acesso aberto (Open Access)
Ensaios estereológicos e morfologia tridimensional na formação hipocampal de aves migratórias marinhas: análise quantitativa da imunomarcação seletiva de neurônios e micróglia em Calidris pusilla e Actitis macularia
(Universidade Federal do Pará, 2013-08-14) DINIZ, Cristovam Guerreiro; SHERRY, David Francis; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
The aim of this report is to describe the hippocampal formation of two migratory birds, Calidris pusilla and Actitis macularia, that leave the cold regions of the Canadian Tundra, escaping the winter, towards the coast of South America and the Caribbean Islands where they remain until winter ends returning to the Northern hemisphere. We intend to describe the qualitative and quantitative morphological organization of the hippocampal formation, using cytoarchitetonics with cresyl violet and immunostaining for neurons and microglia, followed by stereological estimates of the total number of cells identified with selective markers. We intend as well to compare the three-dimensional morphology of hippocampal microglia of these species with those of the dentate gyrus of Wistar rats and Capuchin monkey. The shorebirds used in the characterization were captured in Canela Island, Bragança City, State of Pará, Brazil (0°47'21.95"S and 46°43'7.34"W), as well as in Canada, in the Bay of Fundy, near Johnson's Mills, New Brunswick (45° 50' 19.3" N 64° 31' 5.39" W). The hippocampal formation limits definition was performed employing Nissl staining and immunostaining for NeuN. For the objects of interest definition of stereological estimates and three-dimensional reconstructions we used immunostaining with anti NeuN for neurons and anti-IBA-1 for microglia respectively. The stereological results revealed similar number of neurons in both species whereas the number of microglia in Actitis macularia was 37% higher than in Calidris pusilla. Furthermore, it was found that the hipocampal formation average volume in Actitis macularia was 38% higher than that found in Calidris pusilla. Comparative studies of the microglial morphology with mammals (Rattus novergicus and Cebus apella) revealed significant morphological differences that indicate microglia in birds shows on average lower complexity (smaller fractal dimension), smaller tree volumes and areas and thinner branches than rat and monkey microglia.
Acesso aberto (Open Access)
Envelhecimento e proteção cognitiva: influências da escolaridade e da aptidão física
(Universidade Federal do Pará, 2016-07-25) TORRES, Natáli Valim Oliver Bento; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
Clinical and hematological evaluations were used to study the influence of age, formal education and physical fitness on cognitive performances of two aged groups. For this purpose, three independent experiments were designed. In the first we investigated the influences of age and low education on cognitive performance of healthy elderly. In the second we investigated possible associations between cognitive age-associated cognitive decline, level of physical activity and platelet volume, an indirect peripheral marker of inflammation. In the third we compared age matched healthy elderly with Alzheimer's disease patients, where it is promptly recognized the contribution of inflammation to accelarate disease progression. To measure the influence of education, we used selected tests of the Cambridge Automated Neuropsychological Battery (CANTAB), minimizing the influence of socio-cultural and educational variables, usually present in classical (paper and pencil) psychometric procedures. Thus, sustained visual attention, reaction time, spatial working memory and episodic learning and memory were measured in 182 elderlies. Based on medical history, visual acuity examination and mini-mental state examination (MMSE) we established inclusion criteria as follow: visual acuity 20/30 or higher, no previous or current history of head trauma, stroke, chronic alcoholism, neurological diseases, subjective complains of memory and absence of psychiatric illness, including major depression. Also excluded the volunteers with clinical and / or hematological signs of active infection. Subjects were grouped according to the education level (1 to 7 and ≥ 8 years of schooling) and age (60-69 and ≥ 70 years of age). Two-way analysis of variance indicated that, on average, education influenced performances on visual attention, learning and memory, reaction time and spatial working memory and age influenced the latency on reaction time test. The results suggest that improvement of education should be one of the targets of preventative actions to minimize age-related cognitive decline and that CANTAB might be used to detect subtle cognitive decline in healthy aging. In the study that measured potential associations between platelet morphological changes, physical activity and age-related cognitive decline, we adopted the same exclusion criteria used in the first assay and evaluated 152 healthy elderlies. International Physical Activity Questionnaire (IPAQ - long form) and physical fitness was adopted as indicators of physical activity levels. Physical fitness was assessed by measurements of agility, muscle strength of lower limbs and aerobic capacity. The inclusion criteria based on physical activity self-report only included volunteers performing supervised physical activities at least three times a week, while the inclusion of sedentary elderly demanded that such activities have been not conducted for six consecutive months preceding assessment. All volunteers who participated in the study showed normal test scores of MMSE. Compared to the sedentary group, active elderly showed significant higher performance in all physical tests, sustained visual attention and reaction time, and these results were associated with lower platelet volumes. Significant correlations were found between platelet volumes and performances on learning and memory, rapid visual processing and sustained attention. In the study comparing the platelet morphology of patients with Alzheimer's disease with healthy elderly individuals we found that AD volunteers showed significantly higher platelet volumes associated with poor performance in MMSE. Taken together the results show that physical fitness and physical activity are associated with lower platelet volume and less cognitive decline during aging. The major and minor mean platelet volumes found respectively in patients with Alzheimer's disease and elderly who exercise regularly, suggests that this parameter, usually ignored in haematological routine analysis, appears to have potential value to encourage preventative actions.
Acesso aberto (Open Access)
Estudo exploratório de alterações na linguagem em pacientes com Alzheimer em indivíduos com baixa escolaridade
(Universidade Federal do Pará, 2014-03-21) LIEBENTRITT, Edilene Maia; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
The present report describes features of the language, especially some of the discursive aspects of healthy elderly or with mild cognitive decline or with mild or moderate Alzheimer's disease. A total of 44 elderly were evaluated, including 22 healthy, 4 with mild cognitive decline, 9 with mild Alzheimer disease and 9 with moderate Alzheimer's disease, classified by the CDR criteria. Mini-mental state examination, the short version of Boston naming, verbal fluency and narrative tests by visual confrontation (based on the oral description of picture cookie theft) were applied. Performances were estimated on the selected tests and the oral narratives were classified and assessed using Groves - Wright criteria. Parametric statistical tests were applied and the level of significant statistical differences was set at p<0.05. An inventory and analysis of the lexicon and grammatical categories from the oral narratives were performed using Z scores. To that end the STABLEX software was applied. As compared with mild cognitive decline it was found that semantic verbal fluency is better in the healthy elderly. The narratives showed statistically significant differences between healthy elderly and mild cognitive impairment in the analysis of frequency of use of vocabulary and grammatical categories as a whole, and statistically significant differences between healthy and all other groups in the analysis of each grammatical category. The analysis of the vocabulary and grammatical categories allowed to identify impairments of narrative function as measured by the type of vocabulary and preferred or rejected grammatical categories. The results contribute to distinguish the characteristics of the narrative of healthy elderly, elderly with mild cognitive decline or with mild or moderate Alzheimer's disease, pointing out early changes in language aspects that may possibly be used to evaluate the progression of the disease.
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Influências da idade e do ambiente sobre o curso temporal da infecção pelo vírus da Dengue acentuada por anticorpo heterólogo em modelo murino: ensaios comportamentais e histopatológicos
(Universidade Federal do Pará, 2014-01-03) DINIZ, Daniel Guerreiro; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
Because the enriched environment (EE) increases the activity of T cells, contribute to the immunopathogenesis of dengue virus infections (VDEN) we hypothesized that animals maintained in an enriched environment (AE) compared with animals from impoverished environment of standard laboratory cages (IE), would develop more severe forms of the disease. Because older animals have less functional decline in adaptive immunity T cells, we tested the hypothesis that AE old mice would show higher number of deaths and more intense clinical signs than age-matched IE animals, and this would be associated with greater expansion of T lymphocytes. To test these hypotheses we established scheme of multiple inoculations in adult animals of 9 and 18 months of age. Two regimens of inoculation were tested: multiple injections of single serotype (VDEN3 genotype III) infected brain homogenate (SS) or alternatively multiple injections with that infected brain homogenate followed 24h later by inoculation of heterologous antibody (SSHA). In both cases multiple i.p. inoculations were done. It was found significant differences in the temporal progression of the disease in the animals submitted to one or another scheme of inoculation: SSHA group (Kaplan -Meier log-rank test, p = 0.0025); IUS (Kaplan -Meier log-rank test, p = 0.089). The survival curves of AE and AP under SSHA regime were extended after a single injection of glucocorticoids, reducing the symptoms and the number of deaths, and these effects were greater in the EE group than in the IE (Kaplan-Meier log-rank test, p = 0.0162). In SSHA scheme, EE group showed clinical signs more intense than the AP and those included dyspnea, tremor, hunched posture, immobility, pre-terminal paralysis, shock and eventual death. Compared to the IE group, the AE group regardless of age showed higher mortality and more severe clinical signs. These more severe clinical signs in EE animals under SSHA regime were associated with increased hyperplasia of T lymphocytes in the spleen and increased infiltration of these cells in the liver, lungs and kidneys. Although lymphocytic hyperplasia and infiltration have been more intense in older than in younger animals, immunostaining for viral antigens in target organs was higher in young than in the aged mice. The presence of the virus in various infected organs were confirmed by real time PCR. Taken together the results suggest that the enriched environment life style exacerbates the subsequent inflammatory response to infection, and that is associated with more severe clinical symptoms, higher mortality and increased T cell expansion. Behavioral and histopathological data validate a new immunocompetent murine model for studies on dengue disease allowing in vivo tests of a number of hypothesis raised by epidemiological and in vitro studies.
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Influências do envelhecimento e do ambiente sobre a progressão da encefalite experimental por arbovírus Piry em modelo murino: mudanças morfológicas microgliais e alterações comportamentais
(Universidade Federal do Pará, 2014-10-03) SOUSA, Aline Andrade de; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
Environmental enrichment and aging effects on behavioral and microglial morphological changes were investigated in a murine model of sub-lethal arbovirus encephalitis. To that end two-months-old female albino Swiss mice were raised in impoverished (IE) or in enriched environments (EE) during 6 (young - Y) or 16 (aged - A) months. After behavioral tests, Y and A mice were nasally instilled with an equal volume of Piry virus infected (Py) or normal brain homogenates. Eight days post-infection (DPI), when behavioral tests first revealed sickness changes, mice brains sections were immunoreacted with anti-IBA1 and anti-Piry virus antibodies. At 20 and 40 dpi, the remaining infected animals were behaviorally re-tested, and processed for the same markers. In infected young mice from impoverished environment (IYPy), burrowing activity decreased and recovered earlier (8–10 dpi) than open field activity (20–40 dpi) but remained unaltered in age-matched mice from enriched environment (EYPy). In contrast, aged infected mice, both from enriched (EAPy) and impoverished (IAPy) environments, reduced significantly burrowing activity at all-time windows. Piry virus encephalitis induced transitory olfactory losses in IYPy and EYPy but permanent in IAPy and EAPy. Piry virus antigens immunolabeling reached a peak in CNS parenchyma at 5 and 6dpi and disappeared at 8dpi. All microglia three-dimensional reconstructions were done at 8dpi. Microglial changes were significantly more severe in young adult than in aged mice but EY mice seem to recover to the microglial homeostatic morphology earlier than IY. EE beneficial effects were smaller in aged mice.
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Influências do tamanho da ninhada e da atividade física sobre a plasticidade glial na formação hipocampal em modelo murino
(Universidade Federal do Pará, 2014-02-07) VIANA, Lane Coelho; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
Previous studies have shown significant effects of perinatal stress on cognitive performance in adulthood and during aging. However remains to be studied in detail as exercise at different stages of life helps to reduce these deficits. This is particularly true if we consider previous descriptions of extracellular matrix and glial cell changes, largely ignored in these studies. Thus, the aim of the present report is to investigate possible influences of litter size and physical activity on object recognition memory at adulthood and whether or not these influences affect glial plasticity and extracellular matrix of the hippocampal formation. To that end, we changed the litter size of Wistar rats to accentuate the degree of competition among siblings by functional teats and decrease the amount of maternal care per individual. During the suckling period, we have quantified the maternal care in litters of different sizes. At various time windows we submitted selected subjects to physical exercise on a treadmill, for 5 weeks, adopting the same training protocol. After exercise, some groups of adults and senile animals were submitted to the hippocampal-dependent object recognition memory test, sacrificed, and processed for selective microglia immunolabeling. Other groups of adult animals not subjected to behavioral tests were also euthanized and had one hemisphere used to record diffusional parameters in the hippocampal parenchyma while the other was used for selective immunolabeling to detect astrocytes, NG2 cells and reelin.We found that an increase in litter size was related to the reduction of maternal care, cognitive decline, altered morphology and proliferation of microglia, astrocytes and NG2 cells, as well as to a change in diffusion patterns in the hippocampal stroma. We also demonstrated that these changes may be reversed, at least partially, by physical activity and the extent of these beneficial effects are more pronounced in younger subjects. Finally, we demonstrated that ageing exacerbates microglial morphological changes induced by increased litter size and reduces memory performance.The molecular mechanisms associated to these effects remain to be investigated.
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Memória espacial e morfometria tridimensional da micróglia de CA1 e do giro denteado do Cebus apella
(Universidade Federal do Pará, 2013-10-25) SANTOS FILHO, Carlos; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
This study aims to investigate possible correlations between the morphology of microglia in the hippocampus and dentate gyrus and cognitive performances in individual tests of learning and spatial memory in Cebus apella. Due to the good performance of Cebus apella in hippocampal-dependent cognitive tasks, we used selected tests of Cantab battery successfully used in Old World non-human primates and man. To adapt individuals to the touch screen and to assess spatial learning and memory, Motor Screening Test (MOT) and Paired Associated Learning Test (PAL) were used respectively. To detect possible correlations between microglial morphology and individual performances in the spatal learning and memory tasks, it was necessary to reconstruct and analyze microglial morphological details from the middle and outer one-thirds of the dentate gyrus molecular layer and from the lacunosum molecular layer of CA1, employing three dimensional microscopy. The definition of the boundaries and layers of CA1 and dentate gyrus employed architectural criteria previously defined. For selective microglia immunostaining, it was used polyclonal antibody against the adapter binding ionized calcium Iba -1 protein (anti- Iba1). The occurrence of clusters after multivariate statistical analysis based on microglial morphometric parameters allowed the distinction of at least two major morphological groups of microglia in all individuals. The spatial learning rate and some of the morphometric parameters of microglia from dentate gyrus revealed significant linear and non-linear correlations. In contrast, CA1 did not show any correlation between microglial morphology and behavior. Based on the present and previous studies we suggest that the correlation between cognitive performances and complexity of morphological glial features is not an exclusive attribute of astrocytes and that microglial morphology of the molecular layer of dentate gyrus may be indirectly associated to the performance of individual tests of spatial memory.
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Neurodegeneração crônica em modelo murino: ensaios comportamentais e neuropatológicos na doença prion em fêmeas adultas de camundongos albinos suíços
(Universidade Federal do Pará, 2009-04-30) OLIVEIRA, Roseane Borner de; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
In the present report we described behavioral and neuropathological changes induced by ME7 prion agent inoculated into CA1 of the albino Swiss mice and confirmed previous descriptions in the murine model of prion disease C57Bl6J with two exceptions: 1) septal region present higher level of microglial activation and reactive astrocytosis 2) disease progression (from inoculation to death) is 4 weeks longer and on average, early behavioral changes start correspondently 4 weeks later in albino Swiss mice. Neuronal counts did not reveal any significant changes between the experimental groups. Comparative analysis of activated microglia and perineuronal nets by optical fractionators revealed significant differences between 15 and 18 weeks: the microglial total number increased in this period of time whereas perineuronal nets decreased (t test, two-tailed analysis p<0.05) Cluster and discriminant subsequent analysis applied to behavioral studies revealed that burrowing activity distinguished the occurrence of two subgroups with differential sensitivity to the ME7 agent: one group (40% of the subjects) where the disease progression is faster and the terminal stage is reached in 22 weeks and another one (60%) with slower progression and terminal stage at 26 weeks post-inoculation. The results are important for comparative studies of the immunoneuropathology of chronic neurodegenerative disorders in general and for prion disease itself.
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Semelhanças cognitivas inesperadas entre idosos e jovens: variabilidade e desempenho cognitivo
(Universidade Federal do Pará, 2023-08) JARDIM, Naina Yuki Vieira; TORRES, Natáli Valim Oliver Bento; http://lattes.cnpq.br/1927198788019996; https://orcid.org/0000-0003-0978-211X; DINIZ, Cristovam Wanderley Picanço; http://lattes.cnpq.br/2014918752636286
Interindividual variability in cognitive performances has been investigated as they may provide important clues about the multivariate age-related cognitive decline. In the present work, we searched for cognitive variability, similarities, and differences between older and young people. For this, we used hierarchical cluster and canonical discriminant function analysis of cognitive scores using specific and sensitive tasks from the Cambridge Neuropsychology Test Automated Battery - CANTAB. Among 415 tested volunteers, three distinct cognitive groups were found, mainly based on working memory and episodic memory scores: group 1 (94% young adults) was composed almost exclusively of young adults, while groups 2 (82% older adults) and 3 (95% older adults) were composed predominantly of older adults. Although group 1was the youngest group with the highest level of education compared to the other groups, 18% of young people shared similar performances with older group 2 while 5% shared cognitive similarities with group 3. As compared to group 1, predominantly older groups 2 and 3 had equally lower scores in working memory, but as compared to group 3, group 2 showed greater performances in reaction time, sustained attention, and episodic memory. When the hierarchical cluster and discriminant function analyzes were limited to the same age group, we found 4 and 5 distinct clusters among young adults and older people respectively. Episodic memory, sustained attention, and reaction time most contributed to group formation in the older, while working memory and sustained attention contributed to cluster formation of young adults. Cognitive variability across subjects showed significant dispersion in rapid visual processing, spatial working memory, reaction time, and paired associated learning. The comparative analysis of these differences showed that they do not occur in the same direction and magnitude between individuals, cognitive domains, and tasks. We found that older adults with greater education and a more active lifestyle must have greater cognitive reserve and, therefore, deviated less from the reference group of young adults. Taken together, our data highlight the importance of studying variability as an instrument for the early detection of subtle cognitive declines and to interpret results that deviate from normality.

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Navegando Teses em Neurociências e Biologia Celular (Doutorado) - PPGNBC/ICB por Orientadores "DINIZ, Cristovam Wanderley Picanço"