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Neurodegeneration associated with ageing is closely linked to oxidative stress (OS) and disrupted calcium homeostasis. Some areas of the brain, like the hippocampus - particularly the CA1 region - have shown a high susceptibility to age-related changes, displaying early signs of pathology and neuronal loss. Antioxidants such as α-tocopherol (αT) have been effective in mitigating the impact of OS during ageing. αT homeostasis is primarily regulated by the α-tocopherol transfer protein (αTTP), which is widely distributed throughout the brain - where it plays a crucial role in maintaining αT levels within neuronal cells. This study investigates the distribution of αTTP in the hippocampus of 4- and 24-month-old Pol µ knockout mice (Pol µ-/-), a delayed-ageing model, and the wild type (Pol µ+/+). We also examine the colocalisation in the stratum oriens (st.or) of CA1 region with the primary interneuron populations expressing calcium-binding proteins (CBPs) (calbindin (CB), parvalbumin (PV), and calretinin (CR)). Our findings reveal that αTTP immunoreactivity (-IR) in the st.or of Pol µ mice is significantly reduced. The density of PV-expressing interneurons (INs) increased in aged mice in both Pol µ genotypes (Pol µ-/- and Pol µ+/+), although the density of PV-positive INs was lower in the aged Pol µ-/- mice compared to wild-type mice. By contrast, CR- and CB-positive INs in Pol µ mice remained unchanged during ageing. Furthermore, double immunohistochemistry reveals the colocalisation of αTTP with CBPs in INs of the CA1 st.or. Our study also shows that the PV/αTTP-positive IN population remains unchanged in all groups. A significant decrease of CB/αTTP-positive INs in young Pol µ-/- mice has been detected, as well as a significant increase in CR/αTTP-IR in older Pol µ-/- animals. These results suggest that the differential expression of αTTP and CBPs could have a crucial effect in aiding the survival and maintenance of the different IN populations in the CA1 st.or, and their coexpression could contribute to the enhancement of their resistance to OS-related damage and neurodegeneration associated with ageing.
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The medial temporal lobe (MTL) is a nidus for neurodegenerative pathologies and therefore an important region in which to study polypathology. We investigated associations between neurodegenerative pathologies and the thickness of different MTL subregions measured using high-resolution post-mortem MRI. Tau, TAR DNA-binding protein 43 (TDP-43), amyloid-ß and α-synuclein pathology were rated on a scale of 0 (absent)-3 (severe) in the hippocampus and entorhinal cortex (ERC) of 58 individuals with and without neurodegenerative diseases (median age 75.0 years, 60.3% male). Thickness measurements in ERC, Brodmann Area (BA) 35 and 36, parahippocampal cortex, subiculum, cornu ammonis (CA)1 and the stratum radiatum lacunosum moleculare (SRLM) were derived from 0.2 × 0.2 × 0.2 mm3 post-mortem MRI scans of excised MTL specimens from the contralateral hemisphere using a semi-automated approach. Spearman's rank correlations were performed between neurodegenerative pathologies and thickness, correcting for age, sex and hemisphere, including all four proteinopathies in the model. We found significant associations of (1) TDP-43 with thickness in all subregions (r = - 0.27 to r = - 0.46), and (2) tau with BA35 (r = - 0.31) and SRLM thickness (r = - 0.33). In amyloid-ß and TDP-43 negative cases, we found strong significant associations of tau with ERC (r = - 0.40), BA35 (r = - 0.55), subiculum (r = - 0.42) and CA1 thickness (r = - 0.47). This unique dataset shows widespread MTL atrophy in relation to TDP-43 pathology and atrophy in regions affected early in Braak stageing and tau pathology. Moreover, the strong association of tau with thickness in early Braak regions in the absence of amyloid-ß suggests a role of Primary Age-Related Tauopathy in neurodegeneration.
Assuntos
Córtex Entorrinal/diagnóstico por imagem , Hipocampo/diagnóstico por imagem , Doenças Neurodegenerativas/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Espessura Cortical do Cérebro , Região CA1 Hipocampal/diagnóstico por imagem , Região CA1 Hipocampal/metabolismo , Região CA1 Hipocampal/patologia , Estudos de Casos e Controles , Proteínas de Ligação a DNA/metabolismo , Córtex Entorrinal/metabolismo , Córtex Entorrinal/patologia , Feminino , Degeneração Lobar Frontotemporal/diagnóstico por imagem , Degeneração Lobar Frontotemporal/metabolismo , Degeneração Lobar Frontotemporal/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Humanos , Doença por Corpos de Lewy/diagnóstico por imagem , Doença por Corpos de Lewy/metabolismo , Doença por Corpos de Lewy/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/metabolismo , Doenças Neurodegenerativas/patologia , Emaranhados Neurofibrilares/patologia , Giro Para-Hipocampal/diagnóstico por imagem , Giro Para-Hipocampal/metabolismo , Giro Para-Hipocampal/patologia , Doença de Pick/diagnóstico por imagem , Doença de Pick/metabolismo , Doença de Pick/patologia , Placa Amiloide/patologia , Paralisia Supranuclear Progressiva/diagnóstico por imagem , Paralisia Supranuclear Progressiva/metabolismo , Paralisia Supranuclear Progressiva/patologia , Lobo Temporal/metabolismo , Lobo Temporal/patologia , alfa-Sinucleína/metabolismo , Proteínas tau/metabolismoRESUMO
Synaptic dysfunction or loss in early stages of Alzheimer's disease (AD) is thought to be a major structural correlate of cognitive dysfunction. Early loss of episodic memory, which occurs at the early stage of AD, is closely associated with the progressive degeneration of medial temporal lobe (MTL) structures of which the transentorhinal cortex (TEC) is the first affected area. However, no ultrastructural studies have been performed in this region in human brain samples from AD patients. In the present study, we have performed a detailed three-dimensional (3D) ultrastructural analysis using focused ion beam/scanning electron microscopy (FIB/SEM) to investigate possible synaptic alterations in the TEC of patients with AD. Surprisingly, the analysis of the density, morphological features and spatial distribution of synapses in the neuropil showed no significant differences between AD and control samples. However, light microscopy studies showed that cortical thickness of the TEC was severely reduced in AD samples, but there were no changes in the volume occupied by neuronal and glial cell bodies, blood vessels, and neuropil. Thus, the present results indicate that there is a dramatic loss of absolute number of synapses, while the morphology of synaptic junctions and synaptic spatial distribution are maintained. How these changes affect cognitive impairment in AD remains to be elucidated.
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Doença de Alzheimer/patologia , Córtex Cerebral/ultraestrutura , Imageamento Tridimensional , Microscopia Eletrônica de Varredura , Sinapses/ultraestrutura , Adulto , Idoso , Idoso de 80 Anos ou mais , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microscopia Eletrônica de Varredura/métodos , Pessoa de Meia-Idade , Neuroglia/patologia , Neuroglia/ultraestrutura , Tamanho do Órgão , Sinapses/patologia , Interface Usuário-ComputadorRESUMO
The medial prefrontal areas 32, 24, 14, and 25 (mPFC) form part of the limbic memory system, but little is known about their functional specialization in humans. To add anatomical precision to structural and functional magnetic resonance imaging (MRI) data, we aimed to identify these mPFC subareas in histological preparations of human brain tissue, determine sulci most consistently related with mPFC areal boundaries, and use these sulci to delineate mPFC areas in MRIs. To achieve this, we obtained three-dimensional MRI data from 11 ex vivo hemispheres and processed them for cyto- and myelo-architectonic analysis. The architectonic boundaries of mPFC areas were identified in histology and cortical surface length and volumes were measured. Unfolded maps of histologically determined boundaries were generated to identify the association of mPFC areal boundaries with sulci across cases. This analysis showed that cingulate and superior rostral were the sulci most consistently related to mPFC areal boundaries. Based on presence/absence and anastomosis between such sulci, 6 sulci patterns in the 11 hemispheres were found. A further analysis of 102 hemispheres of in vivo MRI scans (N = 51 males, mean ± SD 24.1 ± 3.1 years of age) showed similar sulci patterns, which allowed us to delineate the mFPC areas in them. The volumes of mPFC areas across histological, ex vivo and in vivo MRI delineations were comparable and probabilistic maps generated from the MRIs of the102 hemispheres. Probabilistic maps of mPFC areas were registered to MNI space and are available for regional analysis of functional magnetic resonance imaging data.
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Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Córtex Pré-Frontal/anatomia & histologia , Córtex Pré-Frontal/diagnóstico por imagem , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Córtex Pré-Frontal/citologia , Adulto JovemRESUMO
Vitamin C (Vit C) is an important antioxidant, exerts powerful neuroprotective brain effects and plays a role in neuronal development and maturation. Vit C is present in brain tissue at higher concentrations than in other organs, but its detailed distribution in brain is unknown. Immunohistochemical detection of this vitamin has been performed by using a highly specific antibody against Vit C. The aim of the present work was to analyze the distribution of Vit C in children's brainstems during postnatal development, comparing two groups of ages: younger and older than one year of life. In general, the same areas showing neurons with Vit C in young cases are also immunostained at older ages. The distribution of neurons containing Vit C was broader in the brainstems of older children, suggesting that brainstem neurons maintain or even increase their ability to retain Vit C along the life span. Immunohistochemical labeling revealed only cell bodies containing this vitamin, and no immunoreactive fibers were observed. The distribution pattern of Vit C in children's brainstems suggests a possible role of Vit C in brain homeostatic regulation. In addition, the constant presence of Vit C in neurons of locus coeruleus supports the important role of Vit C in noradrenaline synthesis, which seemed to be maintained along postnatal development.
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Ácido Ascórbico/metabolismo , Tronco Encefálico/crescimento & desenvolvimento , Tronco Encefálico/metabolismo , Antioxidantes/metabolismo , Criança , Pré-Escolar , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Locus Cerúleo/metabolismo , Masculino , Fibras Nervosas/metabolismo , Neurônios/metabolismoRESUMO
Auditory recognition memory in non-human primates differs from recognition memory in other sensory systems. Monkeys learn the rule for visual and tactile delayed matching-to-sample within a few sessions, and then show one-trial recognition memory lasting 10-20 min. In contrast, monkeys require hundreds of sessions to master the rule for auditory recognition, and then show retention lasting no longer than 30-40 s. Moreover, unlike the severe effects of rhinal lesions on visual memory, such lesions have no effect on the monkeys' auditory memory performance. The anatomical pathways for auditory memory may differ from those in vision. Long-term visual recognition memory requires anatomical connections from the visual association area TE with areas 35 and 36 of the perirhinal cortex (PRC). We examined whether there is a similar anatomical route for auditory processing, or that poor auditory recognition memory may reflect the lack of such a pathway. Our hypothesis is that an auditory pathway for recognition memory originates in the higher order processing areas of the rostral superior temporal gyrus (rSTG), and then connects via the dorsolateral temporal pole to access the rhinal cortex of the medial temporal lobe. To test this, we placed retrograde (3% FB and 2% DY) and anterograde (10% BDA 10,000 mW) tracer injections in rSTG and the dorsolateral area 38 DL of the temporal pole. Results showed that area 38DL receives dense projections from auditory association areas Ts1, TAa, TPO of the rSTG, from the rostral parabelt and, to a lesser extent, from areas Ts2-3 and PGa. In turn, area 38DL projects densely to area 35 of PRC, entorhinal cortex (EC), and to areas TH/TF of the posterior parahippocampal cortex. Significantly, this projection avoids most of area 36r/c of PRC. This anatomical arrangement may contribute to our understanding of the poor auditory memory of rhesus monkeys.
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The postnatal development of the human hippocampal formation establishes the time and place at which we start autobiographical memories. However, data concerning the maturation of the neurochemical phenotypes characteristic of interneurons in the human hippocampus are scarce. We have studied the perinatal and postnatal changes of the dentate gyrus (DG) interneuron populations at three rostrocaudal levels. Immunohistochemically identified neurons and fibers for somatostatin (SOM-12 and SOM-28) and neuropeptide Y (NPY) and the co-localization of SOM-28 and NPY were analyzed. In total, 13 cases were investigated from late pregnancy (1 case), perinatal period (6 cases), first year (1 case), early infancy (3 cases), and late infancy (2 cases). Overall, the pattern of distribution of these peptides in the DG was similar to that of the adult. The distribution of cells was charted, and the cell density (number of positive cells/mm(2)) was calculated. The highest density corresponded to the polymorphic cell layer and was higher at pre- and perinatal periods. At increasing ages, neuron density modifications revealed a decrease from 5 postnatal months onward. In contrast, by late infancy, two immunoreactive bands for SOM-28 and NPY in the molecular layer were much better defined. Double-immunohistochemistry showed that NPY-positive neurons co-localized with SOM-28, whereas some fibers contained only one or other of the neuropeptides. Thus, this peptidergic population, presumably inhibitory, probably has a role in DG maturation and its subsequent functional activity in memory processing.
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Envelhecimento/metabolismo , Giro Denteado/crescimento & desenvolvimento , Giro Denteado/metabolismo , Neurônios/metabolismo , Neuropeptídeo Y/metabolismo , Somatostatina/metabolismo , Adulto , Giro Denteado/citologia , Feminino , Humanos , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Neurônios/citologiaRESUMO
Perinatal asphyxia and hypoxia are common causes of morbidity in neonates. Prenatal birth associated with hypoxemia often results in several disorders because of the lack of oxygen in the brain. Survival rates from perinatal hypoxia have improved, but appropriate treatments for recovery are still limited, with great impact on patients, their families, society in general and health systems. The aim of this work is to contribute to a better understanding of the cellular mechanisms underlying the brainstem responses to hypoxia. For this purpose, distributions of two proteins, hypoxia-inducible factor-1 alpha (HIF-1α) and microtubule-associated protein 2 (MAP-2) were analyzed in brainstems of 11 children, four of them showing neuropathological evidence of brain hypoxia. They were included in control or hypoxic groups, and then in several subgroups according to their age. Immunohistochemical labeling for these proteins revealed only cell bodies containing HIF-1α, and both cell bodies and fibers positive for MAP-2 in the children's brainstems. The distribution of HIF-1α was more restricted than that of MAP-2, and it can be suggested that the expression of HIF-1α increased with age. The distribution pattern of MAP-2 in the medulla oblongata could be more due to age-related changes than to a response to hypoxic damage, whereas in the pons several regions, such as the nucleus ambiguus or the solitary nucleus, showed different immunolabeling patterns in controls and hypoxic cases. The distribution patterns of these two proteins suggest that some brainstem regions, such as the reticular formation or the central gray, could be less affected by conditions of hypoxia.
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Tronco Encefálico/crescimento & desenvolvimento , Tronco Encefálico/metabolismo , Hipóxia Encefálica/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Hipóxia/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Tronco Encefálico/patologia , Criança , Pré-Escolar , Feminino , Humanos , Hipóxia/patologia , Hipóxia Encefálica/patologia , Hipóxia-Isquemia Encefálica/metabolismo , Hipóxia-Isquemia Encefálica/patologia , Imuno-Histoquímica , Lactente , Recém-Nascido , Masculino , Bulbo/crescimento & desenvolvimento , Bulbo/metabolismo , Bulbo/patologia , Neurônios/metabolismo , Neurônios/patologia , Fotomicrografia , Ponte/crescimento & desenvolvimento , Ponte/metabolismo , Ponte/patologia , Núcleo Solitário/crescimento & desenvolvimento , Núcleo Solitário/metabolismo , Núcleo Solitário/patologiaRESUMO
Acid-sensing ion channel 2 (ASIC2) is a member of the degenerin/epithelial sodium channel superfamily, presumably involved mechanosensation. Expression of ASIC2 has been detected in mechanosensory neurons as well as in both axons and Schwann-like cells of cutaneous mechanoreceptors. In these studies we analysed expression of ASIC2 in the cutaneous sensory corpuscles of Macaca fascicularis using immunohistochemistry and laser confocal-scanner microscopy. ASIC2 immunoreactivity was detected in both Meissner and Pacinian corpuscles. It was found to co-localize with neuron-specific enolase and RT-97, but not with S100 protein, demonstrating that ASIC2 expression is restricted to axons supplying mechanoreceptors. These results demonstrate for the first time the presence of the protein ASIC2 in cutaneous rapidly adapting low-threshold mechanoreceptors of monkey, suggesting a role of this ion channel in touch sense.
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Mecanorreceptores/metabolismo , Proteínas do Tecido Nervoso/biossíntese , Corpúsculos de Pacini/metabolismo , Canais de Sódio/biossíntese , Percepção do Tato/fisiologia , Canais Iônicos Sensíveis a Ácido , Animais , Axônios/metabolismo , Imuno-Histoquímica , Macaca fascicularis , Masculino , Microscopia Confocal , Proteínas do Tecido Nervoso/análise , Canais de Sódio/análiseRESUMO
The temporal pole (TP) is the rostralmost portion of the human temporal lobe. Characteristically, it is only present in human and nonhuman primates. TP has been implicated in different cognitive functions such as emotion, attention, behavior, and memory, based on functional studies performed in healthy controls and patients with neurodegenerative diseases through its anatomical connections (amygdala, pulvinar, orbitofrontal cortex). TP was originally described as a single uniform area by Brodmann area 38, and von Economo (area TG of von Economo and Koskinas), and little information on its cytoarchitectonics is known in humans. We hypothesize that 1) TP is not a homogenous area and we aim first at fixating the precise extent and limits of temporopolar cortex (TPC) with adjacent fields and 2) its structure can be correlated with structural magnetic resonance images. We describe here the macroscopic characteristics and cytoarchitecture as two subfields, a medial and a lateral area, that constitute TPC also noticeable in 2D and 3D reconstructions. Our findings suggest that the human TP is a heterogeneous region formed exclusively by TPC for about 7 mm of the temporal tip, and that becomes progressively restricted to the medial and ventral sides of the TP. This cortical area presents topographical and structural features in common with nonhuman primates, which suggests an evolutionary development in human species.
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Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Giro Para-Hipocampal/anatomia & histologia , Lobo Temporal/anatomia & histologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/citologia , Neurônios/fisiologia , Giro Para-Hipocampal/fisiologia , Lobo Temporal/fisiologia , Adulto JovemRESUMO
Impaired olfaction is an early symptom of Alzheimer disease (AD). This likely to reflect neurodegenerative processes taking place in basal telencephalic structures that mediate olfactory processing, including the anterior olfactory nucleus. Betaeta-amyloid (Abeta) accumulation in AD brain may relate to decline in somatostatin levels: somatostatin induces the expression of the Abeta-degrading enzyme neprilysin and somatostatin deficiency in AD may therefore reduce Abeta clearance. We have investigated the expression of somatostatin in the anterior olfactory nucleus of AD and control brain. We report that somatostatin levels were reduced by approximately 50% in AD brain. Furthermore, triple-immunofluorescence revealed co-localization of somatostatin expression with Abeta (65.43%) with Abeta and tau (19.75%) and with tau (2.47%). These data indicate that somatostatin decreases in AD and its expression may be linked with Abeta deposition.
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Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Bulbo Olfatório/metabolismo , Somatostatina/metabolismo , Proteínas tau/metabolismo , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Feminino , Imunofluorescência , Humanos , Masculino , Pessoa de Meia-Idade , Neprilisina/metabolismo , Transtornos do Olfato/etiologia , Transtornos do Olfato/metabolismo , Transtornos do Olfato/patologia , Bulbo Olfatório/patologiaRESUMO
The hippocampal formation is anatomically and functionally related to the olfactory structures especially in rodents. The entorhinal cortex (EC) receives afferent projections from the main olfactory bulb; this constitutes an olfactory pathway to the hippocampus. In addition to the olfactory system, most mammals possess an accessory olfactory (or vomeronasal) system. The relationships between the hippocampal formation and the vomeronasal system are virtually unexplored. Recently, a centrifugal projection from CA1 to the accessory olfactory bulb has been identified using anterograde tracers. In the study reported herein, experiments using anterograde tracers confirm this projection, and injections of retrograde tracers show the distribution and morphology of a population of CA1 and ventral subicular neurons projecting to the accessory olfactory bulb of rats. These results extend previous descriptions of hippocampal projections to the accessory olfactory bulb by including the ventral subiculum and characterizing the morphology, neurochemistry (double labeling with somatostatin), and distribution of such neurons. These data suggest feedback hippocampal control of chemosensory stimuli in the accessory olfactory bulb. Whether this projection processes spatial information on conspecifics or is involved in learning and memory processes associated with chemical stimuli remains to be elucidated.
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Hipocampo/anatomia & histologia , Condutos Olfatórios/anatomia & histologia , Órgão Vomeronasal/anatomia & histologia , Animais , Biotina/análogos & derivados , Dextranos , Feminino , Imunofluorescência , Vias Neurais , Neurônios/metabolismo , Ratos , Ratos Sprague-Dawley , Rodaminas , Somatostatina/metabolismoRESUMO
Vertebrates sense chemical signals through the olfactory and vomeronasal systems. In squamate reptiles, which possess the largest vomeronasal system of all vertebrates, the accessory olfactory bulb projects to the nucleus sphericus, which in turn projects to a portion of the ventral striatum known as olfactostriatum. Characteristically, the olfactostriatum is innervated by neuropeptide Y, tyrosine hydroxylase and serotonin immunoreactive fibers. In this study, the possibility that a structure similar to the reptilian olfactostriatum might be present in the mammalian brain has been investigated. Injections of dextran-amines have been aimed at the posteromedial cortical amygdaloid nucleus (the putative mammalian homologue of the reptilian nucleus sphericus) of rats and mice. The resulting anterograde labeling includes the olfactory tubercle, the islands of Calleja and sparse terminal fields in the shell of the nucleus accumbens and ventral pallidum. This projection has been confirmed by injections of retrograde tracers into the ventral striato-pallidum that render retrograde labeling in the posteromedial cortical amygdaloid nucleus. The analysis of the distribution of neuropeptide Y, tyrosine hydroxylase, serotonin and substance P in the ventral striato-pallidum of rats, and the anterograde tracing of the vomeronasal amygdaloid input in the same material confirm that, similar to reptiles, the ventral striatum of mammals includes a specialized vomeronasal structure (olfactory tubercle and islands of Calleja) displaying dense neuropeptide Y-, tyrosine hydroxylase- and serotonin-immunoreactive innervations. The possibility that parts of the accumbens shell and/or ventral pallidum could be included in the mammalian olfactostriatum cannot be discarded.
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Gânglios da Base/fisiologia , Órgão Vomeronasal/anatomia & histologia , Órgão Vomeronasal/fisiologia , Vias Aferentes/anatomia & histologia , Vias Aferentes/fisiologia , Animais , Biotina/análogos & derivados , Biotina/metabolismo , Dextranos/metabolismo , Feminino , Fluoresceínas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neuropeptídeo Y/metabolismo , Ratos , Ratos Sprague-Dawley , Serotonina/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismoRESUMO
The hippocampal formation is a key structure in memory formation and consolidation. The hippocampus receives information from different cortical and subcortical sources. Cortical information is mostly funneled to the hippocampus through the entorhinal cortex (EC) in a bi-directional way that ultimately ends in the cortex. Retrograde tracing studies in the nonhuman primate indicate that more than two-thirds of the cortical afferents to the EC come from polymodal sensory association areas. Although some evidence for the projection from visual unimodal cortex to the EC exists, inputs from other visual and auditory unimodal association areas, and the possibility of their convergence with polymodal input in the EC remains largely undisclosed. We studied 10 Macaca fascicularis monkeys in which cortical deposits of the anterograde tracer biotinylated dextran-amine were made into different portions of visual and auditory unimodal association cortices in the temporal lobe, and in polymodal association cortex at the upper bank of the superior temporal sulcus. Visual and auditory unimodal as well as polymodal cortical areas projected to the EC. Both visual unimodal and polymodal association cortices presented dense projections, while those from unimodal auditory association cortex were more patchy and less dense. In all instances, the projection distributed in both the superficial and deep layers of the EC. However, while polymodal cortex projected to all layers (including layer I), visual unimodal cortex did not project to layer I, and auditory unimodal cortex projected less densely, scattered through all layers. Topographically, convergence from the three cortical areas studied can be observed in the lateral rostral and lateral caudal subfields. The present study suggests that unimodal and polymodal association cortical inputs converge in the lateral EC, thereby providing the possibility for the integration of complex stimuli for internal representations in declarative memory elaboration.
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Córtex Entorrinal/fisiologia , Animais , Córtex Auditivo/anatomia & histologia , Córtex Auditivo/fisiologia , Vias Auditivas/anatomia & histologia , Vias Auditivas/fisiologia , Biotina/análogos & derivados , Giro Denteado/anatomia & histologia , Giro Denteado/fisiologia , Dextranos , Córtex Entorrinal/anatomia & histologia , Corantes Fluorescentes , Macaca fascicularis , Masculino , Córtex Visual/anatomia & histologia , Córtex Visual/fisiologia , Vias Visuais/anatomia & histologia , Vias Visuais/fisiologiaRESUMO
Hippocampal formation plays a prominent role in episodic memory formation and consolidation. It is likely that episodic memory representations are constructed from cortical information that is mostly funnelled through the entorhinal cortex to the hippocampus. The entorhinal cortex returns processed information to the neocortex. Retrograde tracing studies have shown that neocortical afferents to the entorhinal cortex originate almost exclusively in polymodal association cortical areas. However, the use of retrograde studies does not address the question of the laminar and topographical distribution of cortical projections within the entorhinal cortex. We examined material from 60 Macaca fascicularis monkeys in which cortical deposits of either (3)H-amino acids or biotinylated dextran-amine as anterograde tracers were made into different cortical areas (the frontal, cingulate, temporal and parietal cortices). The various cortical inputs to the entorhinal cortex present a heterogeneous topographical distribution. Some projections terminate throughout the entorhinal cortex (afferents from medial area 13 and posterior parahippocampal cortex), while others have more limited termination, with emphasis either rostrally (lateral orbitofrontal cortex, agranular insular cortex, anterior cingulate cortex, perirhinal cortex, unimodal visual association cortex), intermediate (upper bank of the superior temporal sulcus, unimodal auditory association cortex) or caudally (parietal and retrosplenial cortices). Many of these inputs overlap, particularly within the rostrolateral portion of the entorhinal cortex. Some projections were directed mainly to superficial layers (I-III) while others were heavier to deep layers (V-VI) although areas of dense projections typically spanned all layers. A primary report will provide a detailed analysis of the regional and laminar organization of these projections. Here we provide a general overview of these projections in relation to the known neuroanatomy of the entorhinal cortex.
Assuntos
Córtex Entorrinal/anatomia & histologia , Macaca fascicularis/anatomia & histologia , Animais , Córtex Entorrinal/fisiologia , Hipocampo/anatomia & histologia , Hipocampo/fisiologia , Memória/fisiologia , Neocórtex/anatomia & histologia , Neocórtex/fisiologiaRESUMO
INTRODUCTION: Atrophy of the hippocampus, amygdala and entorhinal cortex can be found in neurodegenerative diseases, head trauma and epilepsy and are expressed by means of volume reductions. The ability to detect these changes quantitatively depends on accurate comparisons with normative databases. AIM: To present standard magnetic resonance imaging (MRI) volumes of the mesio-temporal lobe structures and an objective statistical methodology for contrasting pathological states. SUBJECTS AND METHODS: Volumes of the right and left hippocampi, amygdalae and entorhinal cortex were measured from MRI in 34 right-handed healthy volunteers, aged 19-52 years. Data were normalized for the individual variation in total intracranial volume. Reproducibility was confirmed by intra/inter-observer tests. The statistical analyses included asymmetry comparisons, correlations between volumes and tests to assess the influence of age, gender and general morphometry (body mass index and height). For each volume, we further defined a normative interval by means of 99% confidence ellipses, accordingly to Hotteling's method. RESULTS: Right-left asymmetry in the volumes of the hippocampus and entorhinal cortex was a normal finding. Structures located in the right hemisphere were larger than the left by a small but statistically significant amount. No asymmetry was found in the amygdala. There was no correlation in-between these volumes. Gender differences were exclusively noted in the absolute amygdala volumes (male > female) but were eliminated by the normalization procedure. No effect of age or morphometry was seen in the absolute or normalized volumes (except for a milder correlation between hippocampal volumes and height). Confidence ellipses were built for every structure and provided a precise reading of the data. Particularly, it allowed for a clear distinction of pathological asymmetries and bilateral cases. CONCLUSION: These normative volumes serve as a reference for the assessment of pathologic groups within similar age-range. The use of a single graphic representation simplifies the clinical interpretation and enhances the precision of the results.
Assuntos
Tonsila do Cerebelo/anatomia & histologia , Bases de Dados Factuais , Córtex Entorrinal/anatomia & histologia , Hipocampo/anatomia & histologia , Adulto , Fatores Etários , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , PortugalRESUMO
The distribution of thiamine-immunoreactive structures was studied in the brain of the monkey using an indirect immunoperoxidase technique. Fibers containing thiamine, but no thiamine-immunoreactive cell bodies, were found. The highest density of fibers containing thiamine was observed in the pulvinar nucleus and in the region extending from the pulvinar nucleus to the caudate nucleus. In the mesencephalon, immunoreactive fibers containing thiamine were only found at rostral level close to the medial lemniscus (at the mesencephalic-diencephalic junction). In the thalamus, the distribution of thiamine-immunoreactive structures was more widespread. Thus, immunoreactive fibers were found in nuclei close to the midline (centrum medianum/parafascicular complex), in the ventrolateral thalamus (medial geniculate nucleus, inferior pulvinar nucleus), and in the dorsolateral thalamus (lateral posterior nucleus, pulvinar nucleus). Finally, in the anterior commissure and in the cerebral cortex a low density immunoreactive fibers was visualized. Thus, in the brainstem, no immunoreactive structures were visualized in the medulla oblongata, pons, or in the medial-caudal mesencephalon, and no immunoreactive fibers were observed in the cerebellum, hypothalamus and in the basal ganglia. The present report describes the first visualization and the morphological characteristics (thick, smooth and short, medium or long in length) of the thiamine-immunoreactive fibers in the primate central nervous system using an antiserum directed against this vitamin. The distribution of thiamine-immunoreactive structures in the monkey brain suggests that this vitamin could be involved in several physiological mechanisms.
Assuntos
Encéfalo/citologia , Fibras Nervosas/metabolismo , Fibras Nervosas/fisiologia , Tiamina/metabolismo , Tiamina/fisiologia , Animais , Especificidade de Anticorpos , Química Encefálica , Mapeamento Encefálico , Imuno-Histoquímica , Macaca fascicularis , Masculino , Mesencéfalo/metabolismoRESUMO
Using an antiserum directed against the vitamin riboflavin, we studied the distribution of riboflavin-like immunoreactive structures in the monkey brain. In the mesencephalon, at the level of the mesencephalic-diencephalic junction, single riboflavin-like immunoreactive fibers were observed in its dorsal part, whereas a low density of immunoreactive fibers was found below the surface of the section and close to substantia nigra, and a high density was observed above the substantia nigra and close to the medial geniculate nucleus. In the thalamus, single riboflavin-like immunoreactive fibers were found in the ventral regions of the lateral posterior and the medial geniculate nuclei; a low density in the region located above the medial and lateral geniculate nuclei and a high density in the ventral part of the pulvinar nucleus and in the region extending from this latter to the caudate nucleus. Immunoreactive fibers were not observed in the medulla oblongata, pons, cerebellum, hypothalamus, basal ganglia and cerebral cortex. Moreover, no riboflavin-like immunoreactive cell bodies were observed in the monkey brain. The distribution of riboflavin-like immunoreactive fibers in the monkey suggests that this vitamin could be involved in several physiological mechanisms.
Assuntos
Imuno-Histoquímica , Mesencéfalo/química , Riboflavina/análise , Tálamo/química , Animais , Imuno-Histoquímica/métodos , Macaca fascicularis , Masculino , Mesencéfalo/citologia , Fibras Nervosas/química , Reprodutibilidade dos Testes , Tálamo/citologiaRESUMO
Convergence of sensory modalities in the nonhuman primate cerebral cortex is still poorly understood. We present an anatomical tracing study in which polysensory association cortex located at the fundus and upper bank of the rostral superior temporal sulcus presents reciprocal connections with primary olfactory structures. At the same time, projections from this polysensory area reach multiple primary olfactory centres. Retrograde (Fast Blue) and anterograde (biotinylated dextran-amine and 3H-amino acids) tracers were injected into primary olfactory structures and rostral superior temporal sulcus. Retrograde tracers restricted to the anterior olfactory nucleus resulted in labelled neurons in the rostral portion of the upper bank and fundus of superior temporal sulcus. Injections of biotinylated dextran-amine at the fundus and upper bank of the superior temporal sulcus confirmed this projection by labelling axons in the dorsal and lateral portions of the anterior olfactory nucleus, as well as piriform, periamygdaloid and entorhinal cortices. Retrograde tracer injections at the rostral superior temporal sulcus resulted in neuronal labelling in the anterior olfactory nucleus, piriform, periamygdaloid and entorhinal cortices, thus providing confirmation of the reciprocity between primary olfactory structures and the cortex at the rostral superior temporal sulcus. The reciprocal connections between the rostral part of superior temporal sulcus and primary olfactory structures represent a convergence for olfactory and other sensory modalities at the cortex of the rostral temporal lobe.
Assuntos
Condutos Olfatórios/fisiologia , Lobo Temporal/fisiologia , Aminoácidos/metabolismo , Animais , Biotina/análogos & derivados , Dextranos , Macaca fascicularis , Masculino , Vias Neurais/anatomia & histologia , Vias Neurais/fisiologia , Condutos Olfatórios/anatomia & histologia , Lobo Temporal/anatomia & histologia , Fixação de TecidosRESUMO
The present report describes the first visualization of folic acid-immunoreactive fibers in the mammalian central nervous system using a highly specific antiserum directed against this vitamin. The distribution of folic acid-immunoreactive structures was studied in the brainstem and thalamus of the monkey using an indirect immunoperoxidase technique. We observed fibers containing folic acid, but no folic acid-immunoreactive cell bodies were found. In the brainstem, no immunoreactive structures were visualized in the medulla oblongata, pons, or in the medial-caudal mesencephalon, since at this location immunoreactive fibers containing folic acid were only found at the rostral level in the dorsolateral mesencephalon (in the mesencephalic-diencephalic junction). In the thalamus, the distribution of folic acid-immunoreactive structures was more widespread. Thus, we found immunoreactive fibers in the midline, in nuclei close to the midline (dorsomedial nucleus, centrum medianum/parafascicular complex), in the ventral region of the thalamus (ventral posteroinferior nucleus, ventral posteromedial nucleus), in the ventrolateral thalamus (medial geniculate nucleus, lateral geniculate nucleus, inferior pulvinar nucleus) and in the dorsolateral thalamus (lateral posterior nucleus, pulvinar nucleus). The highest density of fibers containing folic acid was observed in the dorsolateral mesencephalon and in the pulvinar nucleus. The distribution of folic acid-immunoreactive structures in the monkey brain suggests that this vitamin could be involved in several mechanisms, such as visual, auditory, motor and somatosensorial functions.