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1.
Cereb Cortex ; 27(1): 373-385, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-26464475

RESUMO

Areas of the fusiform gyrus (FG) within human ventral temporal cortex (VTC) process high-level visual information associated with faces, limbs, words, and places. Since classical cytoarchitectonic maps do not adequately reflect the functional and structural heterogeneity of the VTC, we studied the cytoarchitectonic segregation in a region, which is rostral to the recently identified cytoarchitectonic areas FG1 and FG2. Using an observer-independent and statistically testable parcellation method, we identify 2 new areas, FG3 and FG4, in 10 human postmortem brains on the mid-FG. The mid-fusiform sulcus reliably identifies the cytoarchitectonic transition between FG3 and FG4. We registered these cytoarchitectonic areas to the common reference space of the single-subject Montreal Neurological Institute (MNI) template and generated probability maps, which reflect the intersubject variability of both areas. Future studies can relate in vivo neuroimaging data with these microscopically defined cortical areas to functional parcellations. We discuss these results in the context of both large-scale functional maps and fine-scale functional clusters that have been identified within the human VTC. We propose that our observer-independent cytoarchitectonic parcellation of the FG better explains the functional heterogeneity of the FG compared with the homogeneity of classic cytoarchitectonic maps.


Assuntos
Lobo Temporal/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
2.
Neuroimage ; 115: 177-90, 2015 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25937490

RESUMO

Human subgenual anterior cingulate cortex (sACC) is involved in affective experiences and fear processing. Functional neuroimaging studies view it as a homogeneous cortical entity. However, sACC comprises several distinct cyto- and receptorarchitectonical areas: 25, s24, s32, and the ventral portion of area 33. Thus, we hypothesized that the areas may also be connectionally and functionally distinct. We performed structural post mortem and functional in vivo analyses. We computed probabilistic maps of each area based on cytoarchitectonical analysis of ten post mortem brains. Maps, publicly available via the JuBrain atlas and the Anatomy Toolbox, were used to define seed regions of task-dependent functional connectivity profiles and quantitative functional decoding. sACC areas presented distinct co-activation patterns within widespread networks encompassing cortical and subcortical regions. They shared common functional domains related to emotion, perception and cognition. A more specific analysis of these domains revealed an association of s24 with sadness, and of s32 with fear processing. Both areas were activated during taste evaluation, and co-activated with the amygdala, a key node of the affective network. s32 co-activated with areas of the executive control network, and was associated with tasks probing cognition in which stimuli did not have an emotional component. Area 33 was activated by painful stimuli, and co-activated with areas of the sensorimotor network. These results support the concept of a connectional and functional specificity of the cyto- and receptorarchitectonically defined areas within the sACC, which can no longer be seen as a structurally and functionally homogeneous brain region.


Assuntos
Córtex Cerebral/anatomia & histologia , Vias Neurais/anatomia & histologia , Adulto , Vias Aferentes/anatomia & histologia , Vias Aferentes/fisiologia , Idoso , Idoso de 80 Anos ou mais , Tonsila do Cerebelo/anatomia & histologia , Atlas como Assunto , Mapeamento Encefálico , Cadáver , Cognição/fisiologia , Emoções/fisiologia , Feminino , Giro do Cíngulo/anatomia & histologia , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Pessoa de Meia-Idade , Dor/fisiopatologia , Córtex Sensório-Motor/anatomia & histologia , Córtex Sensório-Motor/fisiologia , Caracteres Sexuais
3.
Cereb Cortex ; 23(3): 615-28, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22375016

RESUMO

Human inferior parietal lobule (IPL) plays a key role in various cognitive functions. Its functional diversity, including attention, language, and action processing, is reflected by its structural segregation into 7 cytoarchitectonically distinct areas, each with characteristic connectivity patterns. We hypothesized that commonalities of the cytoarchitectonic, connectional, and functional diversity of the IPL should be reflected by a correlated transmitter receptor-based organization. Since the function of a cortical area requires a well-tuned receptor balance, the densities of 15 different receptors were measured in each IPL area. A hierarchical cluster analysis of the receptor balance revealed a tripartite segregation of the IPL into a rostral, middle, and caudal group. Comparison with other cortical areas showed strong similarities with Broca's region for all 3 groups, with the superior parietal cortex for the middle, and with extrastriate visual areas for the caudal group. Notably, caudal-most area PGp has a receptor fingerprint very similar to that of ventral extrastriate visual cortex. We therefore propose a new organizational model of the human IPL, consisting of 3 clusters, which corresponds to its known cytoarchitectonic, connectional, and functional diversity at the molecular level. This might reflect a general organizational principle of human IPL, beyond specific functional domains.


Assuntos
Mapeamento Encefálico , Lobo Parietal/metabolismo , Receptores de Neurotransmissores/análise , Receptores de Neurotransmissores/biossíntese , Idoso , Autorradiografia , Análise por Conglomerados , Feminino , Humanos , Masculino
4.
PLoS Biol ; 8(9)2010 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-20877713

RESUMO

There is a considerable contrast between the various functions assigned to Broca's region and its relatively simple subdivision into two cytoarchitectonic areas (44 and 45). Since the regional distribution of transmitter receptors in the cerebral cortex has been proven a powerful indicator of functional diversity, the subdivision of Broca's region was analyzed here using a multireceptor approach. The distribution patterns of six receptor types using in vitro receptor autoradiography revealed previously unknown areas: a ventral precentral transitional cortex 6r1, dorsal and ventral areas 44d and 44v, anterior and posterior areas 45a and 45p, and areas op8 and op9 in the frontal operculum. A significant lateralization of receptors was demonstrated with respect to the cholinergic M(2) receptor, particularly in area 44v+d. We propose a new concept of the anterior language region, which elucidates the relation between premotor cortex, prefrontal cortex, and Broca's region. It offers human brain homologues to the recently described subdivision of area 45, and the segregation of the ventral premotor cortex in macaque brains. The results provide a novel structural basis of the organization of language regions in the brain.


Assuntos
Lobo Frontal/metabolismo , Receptores de Superfície Celular/metabolismo , Animais , Autorradiografia , Humanos
5.
Epilepsia ; 53(11): 1987-97, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22957946

RESUMO

PURPOSE: A disturbed balance between excitatory and inhibitory neurotransmission underlies epileptic activity, although reports concerning neurotransmitter systems involved remain controversial. METHODS: We quantified densities of 15 receptors in neocortical biopsies from patients with pharmacoresistant focal temporal lobe epilepsy and autopsy controls, and searched for correlations between density alterations and clinical factors or the occurrence of spontaneous synaptic potentials in vitro. KEY FINDINGS: α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-d-aspartate (NMDA), peripheral benzodiazepine, muscarinic (M)(1) , M(2) , nicotinic, α(1) , α(2h) , serotonin (5-HT)(1A) , and adenosine (A)(1) receptor densities were significantly altered in biopsies. The epileptic cohort was subdivided based on clinical (febrile seizures, hippocampal sclerosis, neocortical pathologies, surgery outcome) or electrophysiologic (spontaneous field potentials) criteria, resulting in different patterns of significantly altered receptor types when comparing a given epileptic group with controls. Only AMPA, kainate, M(2) , and 5-HT(1A) receptors were always significantly altered. γ-Aminobutyric acid (GABA)(A) , GABA(B) , and 5-HT(2) receptor alterations were never significant. Correlation patterns between receptor alterations and illness duration or seizure frequency varied depending on whether the epileptic cohort was considered as a whole or subdivided. SIGNIFICANCE: Neocortical temporal lobe epilepsy is associated with a generalized receptor imbalance resulting in a net potentiation of excitatory neurotransmission. Peripheral benzodiazepine receptor alterations highlight that astrocytes are also impaired by seizure activity.


Assuntos
Epilepsias Parciais/metabolismo , Neocórtex/metabolismo , Receptores de Superfície Celular/metabolismo , Adulto , Idoso , Estudos de Coortes , Eletroencefalografia/métodos , Epilepsias Parciais/fisiopatologia , Feminino , Humanos , Ligantes , Masculino , Pessoa de Meia-Idade , Ligação Proteica/fisiologia , Adulto Jovem
6.
Brain ; 134(Pt 10): 2929-47, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21893592

RESUMO

While the amygdala is considered to play a critical role in temporal lobe epilepsy, conclusions on underlying pathophysiological mechanisms have been derived largely from experimental animal studies. Therefore, the present study aimed to characterize synaptic network interactions, focusing on spontaneous interictal-like activity, and the expression profile of transmitter receptors in the human lateral amygdala in relation to temporal lobe epilepsy. Electrophysiological recordings, obtained intra-operatively in vivo in patients with medically intractable temporal lobe epilepsy, revealed the existence of interictal activity in amygdala and hippocampus. For in vitro analyses, slices were prepared from surgically resected specimens, and sections from individual specimens were used for electrophysiological recordings, receptor autoradiographic analyses and histological visualization of major amygdaloid nuclei for verification of recording sites. In the lateral amygdala, interictal-like activity appeared as spontaneous slow rhythmic field potentials at an average frequency of 0.39 Hz, which occurred at different sites with various degrees of synchronization in 33.3% of the tested slices. Pharmacological blockade of glutamate α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, but not N-methyl-D-aspartate receptors, abolished interictal-like activity, while the γ-aminobutyric acid A-type receptor antagonist bicuculline resulted in a dampening of activity, followed by highly synchronous patterns of slow rhythmic activity during washout. Receptor autoradiographic analysis revealed significantly higher α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, kainate, metabotropic glutamate type 2/3, muscarinic type 2 and adrenoceptor α(1) densities, whereas muscarinergic type 3 and serotonergic type 1A receptor densities were lower in the lateral amygdala from epileptic patients in comparison to autopsy controls. Concerning γ-aminobutyric acid A-type receptors, agonist binding was unaltered whereas antagonist binding sites were downregulated in the epileptic lateral amygdala, suggesting an altered high/low-affinity state ratio and concomitant reduced pool of total γ-aminobutyric acid A-type receptors. Together these data indicate an abnormal pattern of receptor densities and synaptic function in the lateral nucleus of the amygdala in epileptic patients, involving critical alterations in glutamate and γ-aminobutyric acid receptors, which may give rise to domains of spontaneous interictal discharges contributing to seizure activity in the amygdala.


Assuntos
Tonsila do Cerebelo/fisiopatologia , Epilepsia/fisiopatologia , Rede Nervosa/fisiopatologia , Sinapses/fisiologia , Adolescente , Adulto , Idoso , Tonsila do Cerebelo/metabolismo , Criança , Epilepsia/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rede Nervosa/metabolismo , Neurônios/metabolismo , Receptor Muscarínico M2/metabolismo , Receptor 5-HT1A de Serotonina/metabolismo , Receptores de AMPA/metabolismo , Receptores Adrenérgicos alfa 1/metabolismo , Receptores de Glutamato Metabotrópico/metabolismo , Sinapses/metabolismo
7.
Cereb Cortex ; 20(6): 1448-61, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19822572

RESUMO

The human posterior insula was shown to respond to a wide variety of stimulation paradigms (e.g. pain, somatosensory, or auditory processing) in functional imaging experiments. Although various anatomical maps of this region have been published over the last century, these schemes show variable results. Moreover, none can directly be integrated with functional imaging data. Hence, our current knowledge about the structure-function relationships in this region remains limited. We therefore remapped the posterior part of the human insular cortex in 10 postmortem brains using an observer-independent approach. This analysis revealed the existence of 3 cytoarchitectonically distinct areas in the posterior insula. The examined brains were then 3D reconstructed and spatially normalized to the Montreal Neurological Institute single-subject template. Probabilistic maps for each area were calculated by superimposing the individual delineations, and a cytoarchitectonic summary map was computed to chart the regional architectonic organization. These maps can be used to identify the anatomical correlates of functional activations observed in neuroimaging studies and to understand the microstructural correlates of the functional segregation of the human posterior insula.


Assuntos
Mapeamento Encefálico/métodos , Córtex Cerebral/citologia , Modelos Estatísticos , Neurônios/citologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Córtex Cerebral/fisiologia , Feminino , Lateralidade Funcional/fisiologia , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Fibras Nervosas Mielinizadas/fisiologia , Vias Neurais/anatomia & histologia , Vias Neurais/citologia , Vias Neurais/fisiologia , Neurônios/fisiologia
8.
Cereb Cortex ; 20(4): 966-81, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19776344

RESUMO

The visual cortex is the largest sensory modality representation in the neocortex of humans and closely related species, and its size and organization has a central role in discussions of brain evolution. Yet little is known about the organization of visual brain structures in the species closest to humans--the apes--thus, making it difficult to evaluate hypotheses about recent evolutionary changes. The primate visual cortex is comprised of numerous cytoarchitectonically distinct areas, each of which has a specific role in the processing of visual stimuli. We examined the histological organization of striate (V1) and 2 extrastriate (V2 and ventral posterior) cortical areas in humans, 5 ape species, and a macaque. The cytoarchitectural patterns of visual areas were compared across species using quantitative descriptions of cell volume densities and laminar patterns. We also investigated potential scaling relationships between cell volume density and several brain, body, and visual system variables. The results suggest that interspecific variability in the cytoarchitectural organization of visual system structures can arise independently of global brain and body size scaling relationships. In particular, species-specific differences in cell volume density seem to be most closely linked to the size of structures in the visual system.


Assuntos
Evolução Biológica , Mapeamento Encefálico , Hominidae/anatomia & histologia , Hominidae/classificação , Córtex Visual/citologia , Animais , Contagem de Células , Tamanho Celular , Humanos , Neurônios/fisiologia , Especificidade da Espécie , Campos Visuais , Vias Visuais
9.
J Hum Evol ; 58(4): 281-92, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20172590

RESUMO

It has been argued that changes in the relative sizes of visual system structures predated an increase in brain size and provide evidence of brain reorganization in hominins. However, data about the volume and anatomical limits of visual brain structures in the extant taxa phylogenetically closest to humans-the apes-remain scarce, thus complicating tests of hypotheses about evolutionary changes. Here, we analyze new volumetric data for the primary visual cortex and the lateral geniculate nucleus to determine whether or not the human brain departs from allometrically-expected patterns of brain organization. Primary visual cortex volumes were compared to lunate sulcus position in apes to investigate whether or not inferences about brain reorganization made from fossil hominin endocasts are reliable in this context. In contrast to previous studies, in which all species were relatively poorly sampled, the current study attempted to evaluate the degree of intraspecific variability by including numerous hominoid individuals (particularly Pan troglodytes and Homo sapiens). In addition, we present and compare volumetric data from three new hominoid species-Pan paniscus, Pongo pygmaeus, and Symphalangus syndactylus. These new data demonstrate that hominoid visual brain structure volumes vary more than previously appreciated. In addition, humans have relatively reduced primary visual cortex and lateral geniculate nucleus volumes as compared to allometric predictions from other hominoids. These results suggest that inferences about the position of the lunate sulcus on fossil endocasts may provide information about brain organization.


Assuntos
Hominidae/anatomia & histologia , Hylobates/anatomia & histologia , Macaca fascicularis/anatomia & histologia , Pan paniscus/anatomia & histologia , Pan troglodytes/anatomia & histologia , Pongo pygmaeus/anatomia & histologia , Córtex Visual/anatomia & histologia , Animais , Evolução Biológica , Fósseis , Corpos Geniculados/anatomia & histologia , Humanos , Imageamento por Ressonância Magnética , Tamanho do Órgão
10.
Cell Physiol Biochem ; 24(3-4): 291-306, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19710544

RESUMO

Hepatic encephalopathy (HE) in chronic liver disease is characterized by neuropsychiatric and motor disturbances and associated with a net increase of inhibitory neurotransmission. Though many studies, mostly carried out in animal models, have linked dysfunctions of single neurotransmitter systems with the pathogenesis of HE, reports concerning neurotransmitter receptor alterations are controversial. Little is known about the situation in humans. We carried out a multireceptor assessment of HE-associated changes in neurotransmitter receptor densities and affinities in human post-mortem brain samples. Dissociation constants and densities of different binding sites for glutamate, GABA, acetylcholine, norepinephrine, serotonin, dopamine and adenosine were determined by in vitro binding assays and quantitative receptor autoradiography in the motor cortex and putamen of HE and control brains. HE cases do not build a homogeneous group, but differ concerning direction and intensity of binding site density divergences from control values. The acetylcholine M2 binding site dissociation constant was significantly higher in HE brains. Nicotinic acetylcholine and adenosine type 1 and 2A densities were significantly down-regulated in the putamen of HE brains. Our data suggest that neurotransmitter alterations are probably not the primary key factor responsible for the neuropsychiatric and motor disturbances associated with HE.


Assuntos
Gânglios da Base/fisiopatologia , Encefalopatia Hepática/fisiopatologia , Córtex Motor/metabolismo , Córtex Motor/fisiopatologia , Receptores de Neurotransmissores/metabolismo , Acetilcolina/metabolismo , Adenosina/metabolismo , Adulto , Idoso , Autorradiografia , Sítios de Ligação , Estudos de Casos e Controles , Dopamina/metabolismo , Evolução Fatal , Feminino , Ácido Glutâmico/metabolismo , Humanos , Cirrose Hepática/metabolismo , Cirrose Hepática Alcoólica/metabolismo , Masculino , Pessoa de Meia-Idade , Norepinefrina/metabolismo , Ligação Proteica , Serotonina/metabolismo , Ácido gama-Aminobutírico/metabolismo
11.
Hum Brain Mapp ; 30(8): 2336-55, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19034899

RESUMO

The structural and functional organization of the human cingulate cortex is an ongoing focus; however, human imaging studies continue to use the century-old Brodmann concept of a two region cingulate cortex. Recently, a four-region neurobiological model was proposed based on structural, circuitry, and functional imaging observations. It encompasses the anterior cingulate, midcingulate, posterior cingulate, and retrosplenial cortices (ACC, MCC, PCC, and RSC, respectively). For the first time, this study performs multireceptor autoradiography of 15 neurotransmitter receptor ligands and multivariate statistics on human whole brain postmortem samples covering the entire cingulate cortex. We evaluated the validity of Brodmann's duality concept and of the four-region model using a hierarchical clustering analysis of receptor binding according to the degree of similarity of each area's receptor architecture. We could not find support for Brodmann's dual cingulate concept, because the anterior part of his area 24 has significantly higher AMPA, kainate, GABA(B), benzodiazepine, and M(3) but lower NMDA and GABA(A) binding site densities than the posterior part. The hierarchical clustering analysis distinguished ACC, MCC, PCC, and RSC as independent regions. The ACC has highest AMPA, kainate, alpha(2), 5-HT(1A), and D(1) but lowest GABA(A) densities. The MCC has lowest AMPA, kainate, alpha(2), and D(1) densities. Area 25 in ACC is similar in receptor-architecture to MCC, particularly the NMDA, GABA(A), GABA(B), and M(2) receptors. The PCC and RSC differ in the higher M(1) and alpha(1) but lower M(3) densities of PCC. Thus, multireceptor autoradiography supports the four-region neurobiological model of the cingulate cortex.


Assuntos
Giro do Cíngulo/anatomia & histologia , Giro do Cíngulo/metabolismo , Modelos Neurológicos , Idoso , Algoritmos , Autorradiografia , Análise por Conglomerados , Densitometria , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Masculino , Análise Multivariada , Receptores Adrenérgicos/metabolismo , Receptores Colinérgicos/metabolismo , Receptores de Dopamina D1/metabolismo , Receptores de GABA/metabolismo , Receptores de Glutamato/metabolismo , Receptores de Serotonina/metabolismo
12.
Cereb Cortex ; 18(4): 846-67, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17644831

RESUMO

The human superior parietal cortex (SPC; Brodmann areas [BA] 5 and 7) comprises the superior parietal lobule and medial wall of the intraparietal sulcus (mIPS) laterally and the posterior paracentral lobule and precuneus medially. Receptor autoradiographic and functional studies indicate more complex segregations in the SPC than suggested by Brodmann (1909). Differences to other historical maps may be due to anatomical variability between brains and different definition criteria for areas. To provide a reliable anatomical reference of the SPC, we performed an observer-independent cytoarchitectonic mapping of this region in 10 human postmortem brains. Cytoarchitecture was analyzed in cell-body-stained brain sections using gray-level index profiles. Multivariate statistical analysis of profile shape allowed the exact localization of cytoarchitectonic borders and quantification of interareal differences. We identified 3 areas in BA 5 (5L, 5M, and 5Ci), 4 in BA 7 (7PC, 7A, 7P, and 7M), and 1 in the anterior mIPS (hIP3). Locations of their borders relative to macroanatomical landmarks varied considerably between brains and hemispheres. Cytoarchitectonic profiles of areas 5Ci and hIP3 differed most from those of the remaining areas, and differences between subareas were stronger in BA 5 than in BA 7. These areas are possible structural correlates of functional segregations within the SPC.


Assuntos
Mapeamento Encefálico/métodos , Neurônios/citologia , Lobo Parietal/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Técnicas Citológicas/estatística & dados numéricos , Feminino , Fixadores , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Coloração e Rotulagem , Inclusão do Tecido
13.
J Neurosci ; 27(6): 1356-64, 2007 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-17287510

RESUMO

The structural correlates of gender differences in visuospatial processing are essentially unknown. Our quantitative analysis of the cytoarchitecture of the human primary visual cortex [V1/Brodmann area 17 (BA17)], neighboring area V2 (BA18), and the cytoarchitectonic correlate of the motion-sensitive complex (V5/MT+/hOc5) shows that the visual areas are sexually dimorphic and that the type of dimorphism differs among the areas. Gender differences exist in the interhemispheric asymmetry of hOc5 volumes and in the right-hemispheric volumetric ratio of hOc5 to BA17, an area that projects to V5/MT+/hOc5. Asymmetry was also observed in the surface area of hOc5 but not in its cortical thickness. The differences give males potentially more space in which to process additional information, a finding consistent with superior male processing in particular visuospatial tasks, such as mental rotation. Gender differences in hOc5 exist with similar volume fractions of cell bodies, implying that, overall, the visual neural circuitry is similar in males and females.


Assuntos
Dominância Cerebral , Percepção de Movimento/fisiologia , Caracteres Sexuais , Percepção Espacial/fisiologia , Córtex Visual/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Mapeamento Encefálico , Tamanho Celular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neurônios/ultraestrutura , Tamanho do Órgão , Comportamento Espacial/fisiologia , Córtex Visual/fisiologia , Vias Visuais/anatomia & histologia , Vias Visuais/fisiologia
14.
Epilepsia ; 49(10): 1733-48, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18479397

RESUMO

PURPOSE: The astrocyte-specific glutamine synthetase (GS) plays a key role in glutamate recycling and Gamma-aminobutyric acid (GABA) metabolism. Changes in the expression or activity of GS have been proposed to contribute to epileptogenesis. The mechanisms or how and where GS may contribute to epilepsy is still a matter of discussion. Here we asked the question whether brain regions, which show an astrocytic stress response respond with alterations of GS. METHODS: Biochemical and histological alterations of GS, HSP-27, and GFAP were studied after pentylenetetrazole-induced repetitive epileptic seizures (PIRS) in rats using a topographical quantification of the GS-immunoreactivity (GSIR) in relation to the focal heat shock response (HSR). Saline-treated rats served as controls and rats treated by the GS-inhibitor, L-methionine-sulfoximine (MSO) served as a positive control. RESULTS: No changes in the amount of GSIR and GS-protein occurred during PIRS. A significant reduction of GSIR was observed by histochemistry (in situ) and in native (nonheated) protein extracts of MSO-treated rats. In rats affected by PIRS, GS-activity showed a significant, region-specific reduction in association with a nitration of the enzyme. DISCUSSION: These results show that neither PIRS nor GS-inhibition reduced the amount of GS protein, but that MSO interferes with antibody binding to native GS. PIRS resulted in a focal increase of astrocytic stress response, whereas MSO caused a widespread, homogeneous astrocytic HSR independent from quantitative changes of GS content. In rats with PIRS the regions showing a strong glial HSR, respond with reduced GS-activity and GS-nitration, which all together are clear indicators of a nitrosative stress response.


Assuntos
Epilepsia/induzido quimicamente , Epilepsia/metabolismo , Epilepsia/fisiopatologia , Glutamato-Amônia Ligase/metabolismo , Pentilenotetrazol , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Epilepsia/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Proteínas de Choque Térmico HSP27/metabolismo , Imunoprecipitação/métodos , Masculino , Modelos Biológicos , Ratos , Ratos Wistar
15.
Brain Struct Funct ; 223(4): 1637-1666, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29188378

RESUMO

The human amygdala consists of subdivisions contributing to various functions. However, principles of structural organization at the cellular and molecular level are not well understood. Thus, we re-analyzed the cytoarchitecture of the amygdala and generated cytoarchitectonic probabilistic maps of ten subdivisions in stereotaxic space based on novel workflows and mapping tools. This parcellation was then used as a basis for analyzing the receptor expression for 15 receptor types. Receptor fingerprints, i.e., the characteristic balance between densities of all receptor types, were generated in each subdivision to comprehensively visualize differences and similarities in receptor architecture between the subdivisions. Fingerprints of the central and medial nuclei and the anterior amygdaloid area were highly similar. Fingerprints of the lateral, basolateral and basomedial nuclei were also similar to each other, while those of the remaining nuclei were distinct in shape. Similarities were further investigated by a hierarchical cluster analysis: a two-cluster solution subdivided the phylogenetically older part (central, medial nuclei, anterior amygdaloid area) from the remaining parts of the amygdala. A more fine-grained three-cluster solution replicated our previous parcellation including a laterobasal, superficial and centromedial group. Furthermore, it helped to better characterize the paralaminar nucleus with a molecular organization in-between the laterobasal and the superficial group. The multimodal cyto- and receptor-architectonic analysis of the human amygdala provides new insights into its microstructural organization, intersubject variability, localization in stereotaxic space and principles of receptor-based neurochemical differences.


Assuntos
Tonsila do Cerebelo/metabolismo , Mapeamento Encefálico , Vias Neurais/metabolismo , Receptores de Neurotransmissores/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Tonsila do Cerebelo/diagnóstico por imagem , Tonsila do Cerebelo/efeitos dos fármacos , Autopsia , Autorradiografia , Feminino , Lateralidade Funcional , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/diagnóstico por imagem , Neurotransmissores/farmacocinética , Trítio/farmacocinética
16.
Methods Mol Biol ; 401: 267-84, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-18368371

RESUMO

Receptor distributions in the brain are studied by autoradiographic mapping in brain slices, which is a labor-intensive and expensive procedure. To keep track of the results of such studies, we have designed CoReDat, a multi-user relational database system that is available for download from www.cocomac.org/coredat. Here, we describe the data model and provide an architectural overview of CoReDat for the neuroscientist who wants to use this database, adapt it for related purposes, or build a new one.


Assuntos
Mapeamento Encefálico , Encéfalo/anatomia & histologia , Sistemas de Gerenciamento de Base de Dados , Receptores Citoplasmáticos e Nucleares/metabolismo , Animais , Autorradiografia , Humanos , Neuroanatomia/métodos , Software
17.
Brain Struct Funct ; 222(1): 83-99, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-26943919

RESUMO

Healthy aging is accompanied by changes in the functional architecture of the default mode network (DMN), e.g. a posterior to anterior shift (PASA) of activations. The putative structural correlate for this functional reorganization, however, is largely unknown. Changes in gyrification, i.e. decreases of cortical folding were found to be a marker of atrophy of the brain in later decades of life. Therefore, the present study assessed local gyrification indices of the DMN in relation to age and cognitive performance in 749 older adults aged 55-85 years. Age-related decreases in local gyrification indices were found in the anterior part of the DMN [particularly; medial prefrontal cortex (mPFC)] of the right hemisphere, and the medial posterior parts of the DMN [particularly; posterior cingulate cortex (PCC)/precuneus] of both hemispheres. Positive correlations between cognitive performance and local gyrification indices were found for (1) selective attention and left PCC/precuneus, (2) visual/visual-spatial working memory and bilateral PCC/precuneus and right angular gyrus (AG), and (3) semantic verbal fluency and right AG and right mPFC. The more pronounced age-related decrease in local gyrification indices of the posterior parts of the DMN supports the functionally motivated PASA theory by correlated structural changes. Surprisingly, the prominent age-related decrease in local gyrification indices in right hemispheric ROIs provides evidence for a structural underpinning of the right hemi-aging hypothesis. Noticeably, the performance-related changes in local gyrification largely involved the same parts of the DMN that were subject to age-related local gyrification decreases. Thus, the present study lends support for a combined structural and functional theory of aging, in that the functional changes in the DMN during aging are accompanied by comparably localized structural alterations.


Assuntos
Envelhecimento , Córtex Cerebral/anatomia & histologia , Cognição , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/psicologia , Cognição/fisiologia , Feminino , Giro do Cíngulo/anatomia & histologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Lobo Parietal/anatomia & histologia , Córtex Pré-Frontal/anatomia & histologia
18.
Alzheimers Res Ther ; 9(1): 28, 2017 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-28412965

RESUMO

BACKGROUND: Progressive supranuclear palsy (PSP) with a frontal presentation, characterized by cognitive deficits and behavioral changes, has been recognized as an early clinical picture, distinct from the classical so-called Richardson and parkinsonism presentations. The midcingulate cortex is associated with executive and attention tasks and has consistently been found to be impaired in imaging studies of patients with PSP. The aim of the present study was to determine alterations in neurotransmission underlying the pathophysiology of PSP, as well as their significance for clinically identifiable PSP subgroups. METHODS: In vitro receptor autoradiography was used to quantify densities of 20 different receptors in the caudate nucleus and midcingulate area 24' of patients with PSP (n = 16) and age- and sex-matched control subjects (n = 14). RESULTS: Densities of γ-aminobutyric acid type B, peripheral benzodiazepine, serotonin receptor type 2, and N-methyl-D-aspartate receptors were significantly higher in area 24' of patients with PSP, where tau impairment was stronger than in the caudate nucleus. Kainate and nicotinic cholinergic receptor densities were significantly lower, and adenosine receptor type 1 (A1) receptors significantly higher, in the caudate nucleus of patients with PSP. Receptor fingerprints also segregated PSP subgroups when clinical parameters such as occurrence of frontal presentation and tau pathology severity were taken into consideration. CONCLUSIONS: We demonstrate, for the first time to our knowledge, that kainate and A1 receptors are altered in PSP and that clinically identifiable PSP subgroups differ at the neurochemical level. Numerous receptors were altered in the midcingulate cortex, further suggesting that it may prove to be a key region in PSP. Finally, we add to the evidence that nondopaminergic systems play a role in the pathophysiology of PSP, thus highlighting potential novel treatment strategies.


Assuntos
Núcleo Caudado/metabolismo , Giro do Cíngulo/metabolismo , Receptores de Neurotransmissores/metabolismo , Paralisia Supranuclear Progressiva/metabolismo , Idoso , Idoso de 80 Anos ou mais , Autorradiografia , Núcleo Caudado/patologia , Estudos de Coortes , Feminino , Giro do Cíngulo/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Paralisia Supranuclear Progressiva/patologia , Transmissão Sináptica/fisiologia , Proteínas tau/metabolismo
19.
J Comp Neurol ; 495(1): 53-69, 2006 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-16432904

RESUMO

Anatomical studies in the macaque cortex and functional imaging studies in humans have demonstrated the existence of different cortical areas within the intraparietal sulcus (IPS). Such functional segregation, however, does not correlate with presently available architectonic maps of the human brain. This is particularly true for the classical Brodmann map, which is still widely used as an anatomical reference in functional imaging studies. The aim of this cytoarchitectonic mapping study was to use previously defined algorithms to determine whether consistent regions and borders can be found within the cortex of the anterior IPS in a population of 10 post-mortem human brains. Two areas, the human intraparietal area 1 (hIP1) and the human intraparietal area 2 (hIP2), were delineated in serial histological sections of the anterior, lateral bank of the human IPS. The region hIP1 is located posterior and medial to hIP2, and the former is always within the depths of the IPS. The latter, on the other hand, sometimes reaches the free surface of the superior parietal lobule. The delineations were registered to standard reference space, and probabilistic maps were calculated, thereby quantifying the intersubject variability in location and extent of both areas. In the future, they can be a tool for analyzing structure-function relationships and a basis for determining degrees of homology in the IPS among anthropoid primates. We conclude that the human IPS has a more finely grained parcellation than shown in Brodmann's map.


Assuntos
Mapeamento Encefálico/métodos , Vias Neurais/anatomia & histologia , Neurônios/citologia , Lobo Parietal/anatomia & histologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Evolução Biológica , Feminino , Humanos , Citometria por Imagem , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Vias Neurais/fisiologia , Neurônios/fisiologia , Lobo Parietal/fisiologia , Primatas/anatomia & histologia , Primatas/fisiologia , Especificidade da Espécie
20.
Brain Struct Funct ; 221(4): 1877-97, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-25687261

RESUMO

The microstructural correlates of the functional segregation of the human lateral occipital cortex are largely unknown. Therefore, we analyzed the cytoarchitecture of this region in ten human post-mortem brains using an observer-independent and statistically testable parcellation method to define the position and extent of areas in the lateral occipital cortex. Two new cytoarchitectonic areas were found: an anterior area hOc4la and a posterior area hOc4lp. hOc4la was located behind the anterior occipital sulcus in rostral and ventral portions of this region where it occupies the anterior third of the middle and inferior lateral occipital gyri. hOc4lp was found in caudal and dorsal portions of this region where it extends along the superior and middle lateral occipital gyri. The cytoarchitectonic areas were registered to 3D reconstructions of the corresponding brains, which were subsequently spatially normalized to the Montreal Neurological Institute reference space. Continuous probabilistic maps of both areas based on the analysis of ten brains were generated to characterize their inter-subject variability in location and size. The maps of hOc4la and hOc4lp were then used as seeds for meta-analytic connectivity modeling and quantitative functional decoding to identify their co-activation patterns and assignment to functional domains. Convergent evidence from their location, topography, size, functional domains and connectivity indicates that hOc4la and hOc4lp are the potential anatomical correlates of the functionally defined lateral occipital areas LO-1 and LO-2.


Assuntos
Lobo Occipital/citologia , Lobo Occipital/fisiologia , Idoso , Mapeamento Encefálico , Análise por Conglomerados , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Vias Neurais/citologia , Vias Neurais/fisiologia , Técnicas de Rastreamento Neuroanatômico/métodos , Análise de Componente Principal , Córtex Visual/citologia , Córtex Visual/fisiologia
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