RESUMO
The principal events of neocortical histogenesis were anticipated by work published prior to the 20th century. These were neuronal proliferation and migration and the complex events of cortical pattern formation leading to a laminated architecture where each layer is dominated by a principal neuronal class. Work that has followed has extended the knowledge of the workings of the proliferative epithelium, cellular mechanisms of migration and events through which cells are winnowed and then differentiate once their postmigratory positions are established. Work yet ahead will emphasize mechanisms that coordinate the molecular events that integrate proliferation and cell class specification in relation to the final neocortical neural system map.
Assuntos
Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células , Neocórtex/embriologia , Vias Neurais/embriologia , Neurônios/fisiologia , Animais , Linhagem da Célula/genética , Regulação da Expressão Gênica no Desenvolvimento/genética , Humanos , Neocórtex/citologia , Neocórtex/fisiologia , Vias Neurais/citologia , Vias Neurais/fisiologia , Neurônios/classificação , Neurônios/citologia , Transdução de Sinais/genéticaRESUMO
The number of neurons in the neocortex is the product of the size of the preneuronogenetic founder population, that is, the number of proliferative cells that are present at the onset of neuronogenesis, and neuronogenetic amplification occurring as neurons are being produced. The amount of neuronogenetic amplification is determined by changes in the output fraction, Q, from 0 to 1, over a fixed number of cell cycles. Greater neuronogenetic amplification would occur across species if the number of cell cycles during which Q < 0.5 increased. Since neither the length of the cell cycle nor the length of the neuronogenetic interval, that is, time per se, influence neuron number directly, it is speculated that changes in these parameters are essential to neuronal diversity.
Assuntos
Evolução Biológica , Córtex Cerebral/anatomia & histologia , Animais , Córtex Cerebral/crescimento & desenvolvimento , Córtex Cerebral/fisiologia , Humanos , Modelos BiológicosRESUMO
Substantial death of migrating and differentiating neurons occurs within the developing CNS of mice that are deficient in genes required for repair of double-stranded DNA breaks. These findings suggest that large-scale, yet previously unrecognized, double-stranded DNA breaks occur normally in early postmitotic and differentiating neurons. Moreover, they imply that cell death occurs if the breaks are not repaired. The cause and natural function of such breaks remains a mystery; however, their occurrence has significant implications. They might be detected by histological methods that are sensitive to DNA fragmentation and mistakenly interpreted to indicate cell death when no relationship exists. In a broader context, there is now renewed speculation that DNA recombination might be occurring during neuronal development, similar to DNA recombination in developing lymphocytes. If this is true, the target gene(s) of recombination and their significance remain to be determined.
Assuntos
Diferenciação Celular/genética , Fragmentação do DNA/genética , Reparo do DNA , DNA/metabolismo , Neurônios/citologia , Animais , Apoptose , Caspases/metabolismo , Morte Celular/genética , Divisão Celular/genética , Movimento Celular , DNA Ligase Dependente de ATP , DNA Ligases/deficiência , DNA Ligases/genética , Proteínas de Ligação a DNA/deficiência , Proteínas de Ligação a DNA/genética , Camundongos , Neurônios/metabolismoRESUMO
Development of the neocortex of the trisomy 16 (Ts16) mouse, an animal model of Down syndrome (DS), is characterized by a transient delay in the radial expansion of the cortical wall and a persistent reduction in cortical volume. Here we show that at each cell cycle during neuronogenesis, a smaller proportion of Ts16 progenitors exit the cell cycle than do control, euploid progenitors. In addition, the cell cycle duration was found to be longer in Ts16 than in euploid progenitors, the Ts16 growth fraction was reduced, and an increase in apoptosis was observed in both proliferative and postmitotic zones of the developing Ts16 neocortical wall. Incorporation of these changes into a model of neuronogenesis indicates that they are sufficient to account for the observed delay in radial expansion. In addition, the number of neocortical founder cells, i.e., precursors present just before neuronogenesis begins, is reduced by 26% in Ts16 mice, leading to a reduction in overall cortical size at the end of Ts16 neuronogenesis. Thus, altered proliferative characteristics during Ts16 neuronogenesis result in a delay in the generation of neocortical neurons, whereas the founder cell deficit leads to a proportional reduction in the overall number of neurons. Such prenatal perturbations in either the timing of neuron generation or the final number of neurons produced may lead to significant neocortical abnormalities such as those found in DS.
Assuntos
Microcefalia/embriologia , Microcefalia/patologia , Neurônios/fisiologia , Trissomia/patologia , Animais , Apoptose/efeitos dos fármacos , Contagem de Células , Ciclo Celular/fisiologia , Divisão Celular/fisiologia , Núcleo Celular/patologia , Sobrevivência Celular/fisiologia , Córtex Cerebral/patologia , Feminino , Efeito Fundador , Imuno-Histoquímica , Cariotipagem , Camundongos , Camundongos Endogâmicos C57BL , Microcefalia/genética , Neocórtex/citologia , Neocórtex/fisiologia , Trissomia/genéticaRESUMO
BALB/cJ and BALB/cByJ mice are homozygous for the autosomal gene "hippocampal lamination defect" (provisional gene symbol: Hld) which produces an abnormality in the lamination of the pyramidal cell layer of area CA3c of the hippocampus such that early-generated neurons are superficial and late-generated neurons are deep. Other inbred strains of mice are wild-type (+/+) at the Hld locus and do not have this inversion in cell position in area CA3c. The Golgi method was used to analyze the dendritic arbors of the abnormally positioned pyramidal cells and to compare the distribution of dendritic excrescences (i.e., the termination sites of the mossy fibers) in +/+ and Hld/Hld mice. It was found that in +/+ mice the late-generated pyramidal cells (whose cell bodies are positioned just below the suprapyramidal mossy fiber layer) have one set of dendritic excrescences on their apical dendrites as they extend through the suprapyramidal mossy fiber layer and a second set on their basal dendrites as they pass through the infrapyramidal mossy fiber layer. In contrast, in Hld/Hld mice the late-generated pyramidal cells (whose cell bodies are abnormally positioned just below the intrapyramidal mossy fiber layer) have two sets of dendritic excrescences on their apical dendrites, as they pass through the intrapyramidal and suprapyramidal mossy fiber layers, and none on their basal dendrites. In addition, in the vicinity of the apparent point of contact of the intrapyramidal mossy fibers, the apical dendrites of some of the abnormally positioned pyramidal cells have several fine-caliber branches.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Hipocampo/citologia , Animais , Movimento Celular , Dendritos , Hipocampo/crescimento & desenvolvimento , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Mutantes Neurológicos , MutaçãoRESUMO
The site of origin and route and rate of migration of neurons in the developing hippocampal region of the rhesus monkey were studied with tritiated thymidine (3H-TdR) autoradiography. Analysis of specimens sacrificed approximately 1 hour after exposure to 3H-TdR shows that the neurons destined for the hippocampus and subiculum are generated exclusively in the ventricular zone lining the medial wall of the lateral cerebral ventricle. In contrast, neurons of the parahippocampal formation are generated in two proliferative zones: The majority of neurons destined for the lamina principalis interna arise from the ventricular zone, whereas most of those destined for the lamina principalis externa originate from the subventricular zone. The neurons of the dentate gyrus are also generated in two locations: in the ventricular zone (between E38 and E85) and within the prospective hilus of the dentate gyrus (from E58 up to approximately 3 months after birth). Analysis of specimens sacrificed at progressively longer intervals after exposure to 3H-TdR indicates that neurons destined for all of the subdivisions of the hippocampal region (except those cells generated in the hilus of the dentate gyrus) migrate through the intermediate zone, bypassing previously generated neurons on their way to the superficial limits of the developing cortical plate. Estimated migration rates are approximately 15 micrometer/day in the sector of the hippocampal formation, about 100 micrometer/day in the parahippocampal formation, and about 15 micrometer/day in the region of adjacent neocortex. Thus simultaneously generated neurons destined for three distinct cytoarchitectonic areas have significantly different rates of cell migration. These differences are unrelated to the length of cell trajectories and may depend on the mechanism of cell translocation and/or the timing of signals that initiate cell movement. The differential rate of migration indicates that the fate of postmitotic cells may be determined before they have reached their final destination.
Assuntos
Diferenciação Celular , Movimento Celular , Hipocampo/citologia , Envelhecimento , Animais , Autorradiografia , Córtex Cerebral/citologia , Ventrículos Cerebrais/citologia , Feminino , Macaca mulatta , Mitose , Neurônios/citologia , GravidezRESUMO
The time of origin of neurons in the hippocampal region was determined in a series of rhesus monkeys, each of which had been exposed to a pulse of tritiated thymidine (3H-TdR) at a different time during ontogeny and sacrificed between the second and fifth month after birth. No heavily labeled cells were found in the hippocampal region of animals exposed to 3H-TdR before embryonic day 33 (E33). Exposure to 3H-TdR given at E36 labels a few neurons in the deepest layers of the entorhinal area, and 3H-TdR given at E38 labels a small number of neurons in all hippocampal subdivisions. Although the first neurons are generated almost simultaneously throughout the hippocampal region, the proliferation ceases at a different time in each subdivision. The last neurons destined for the entorhinal area and presubiculum are generated between E70 and E75, whereas the last parasubicular neurons are generated between E75 and E80. The production of neurons that form the subiculum ends about two weeks earlier, between E56 and E65. Within the hippocampus, genesis of pyramidal cells ends between E70 and E80 in area CA1, between E56 and E65 in area CA2, between E65 and E80 in area CA1, between E56 and E65 in area CA2, between E65 and E70 in area CA3, and between E75 and E80 in area CA4. In contrast, the genesis of granule cells of the fascia dentata is considerably prolonged. It continues throughout the second half of gestation, declines steadily in the course of the first postnatal month, and tapers off during the next 2 months. There is a distinct inside-to-outside spatiotemporal gradient in the parahippocampal formation and in the stratum pyramidale of both the subiculum and hippocampus. In contrast, the spatiotemporal pattern of granule cell origin in the dentate gyrus is outside-to-inside. Furthermore, granule cells generated between E36 and E80 are distributed in a distinct suprapyramidal-to-infrapyramidal gradient, whereas those generated at later ages are distributed evenly throughout the fascia dentata. Correlation of the present findings with histological data on hippocampal neurogenesis in the human brain demonstrates that the timing and sequence of developmental events as well as spatiotemporal gradients are similar in both primate species.
Assuntos
Diferenciação Celular , Hipocampo/citologia , Envelhecimento , Animais , Autorradiografia , Contagem de Células , Feminino , Macaca mulatta , Mitose , Neurônios/citologia , GravidezRESUMO
We investigated the spatial patterns of synaptic profiles in en passant synapses between the premotor axon of a peripherally synapsing interneuron (PAPSI) and a set of individually identifiable motoneuron axons in Drosophila melanogaster. These synaptic profiles are distributed as the axons travel parallel to each other in a bundle; the synapses begin as the axons leave the thoracic ganglion and continue peripherally for 45-65 microm. We found that the number of synaptic profiles per micron length of the motoneuron axons was greatest close to the ganglion; the cumulative distribution of profiles could be fitted to curves of the form f(x) = alpha(1 - e(-beta x)), where x = the distance from the thoracic ganglion, and alpha and beta are constants. The distribution of synaptic profiles was also examined in a mutant strain, Passover (Pas), known to affect connectivity in a pathway that includes the PAPSI. The synaptic profiles between the PAPSI and the motoneuron axons appeared ultrastructurally unremarkable in Pas. Also, the total number of synaptic profiles between the PAPSI and the motoneuron axons did not differ between Pas and wild type flies. However, the distribution of synaptic profiles among the individual motoneuron axons did differ significantly from wild type flies, as did the area of contiguity between the motoneuron axons and the PAPSI, which was much greater in Pas than in wild type flies.
Assuntos
Drosophila melanogaster/anatomia & histologia , Neurônios Motores/ultraestrutura , Animais , Axônios/fisiologia , Interneurônios/fisiologia , Microscopia Eletrônica , Vias Neurais/fisiologia , Sinapses/fisiologiaRESUMO
The Snell dwarf mouse (Pit1dw-J homozygote) has a mutation in the Pit1 gene that prevents the normal formation of the anterior pituitary. In neonates and adults there is almost complete absence of growth hormone (GH), prolactin (PRL), thyroxin (T4), and thyroid-stimulating hormone (TSH). Since these hormones have been suggested to play a role in normal development of the central nervous system (CNS), we have investigated the effects of the Pit1dw-J mutation on the cerebellum and hippocampal formation. In the cerebellum, there were abnormalities of both foliation and lamination. The major foliation anomalies were 1) changes in the relative size of specific folia and also the proportional sizes of the anterior vs posterior cerebellum; and 2) the presence of between one and three microfolia per half cerebellum. The microfolia were all in the medial portion of the hemisphere in the caudal part of the cerebellum. Each microfolium was just rostral to a normal fissure and interposed between the fissure and a normal gyrus. Lamination abnormalities included an increase in the number of single ectopic granule cells in the molecular layer in both cerebellar vermis (86%) and hemisphere (40%) in comparison with the wild-type mouse. In the hippocampus of the Pit1dw-J homozygote mouse, the number of pyramidal cells was decreased, although the width of the pyramidal cell layer throughout areas CA1-CA3 appeared to be normal, but less densely populated than in the wild-type mouse. Moreover, the number of granule cells that form the granule cell layer was decreased from the wild-type mouse and some ectopic granule cells (occurring both as single cells and as small clusters) were observed in the innermost portion of the molecular layer. The abnormalities observed in the Pit1dw-J homozygote mouse seem to be caused by both direct and indirect effects of the deficiency of TSH (or T4), PRL, or GH rather than by a direct effect of the deletion of Pit1.
Assuntos
Movimento Celular/fisiologia , Córtex Cerebelar/anormalidades , Proteínas de Ligação a DNA/genética , Camundongos Mutantes/anormalidades , Células Piramidais/citologia , Fatores de Transcrição/genética , Animais , Córtex Cerebelar/citologia , Giro Denteado/citologia , Proteínas de Homeodomínio/genética , Homozigoto , Camundongos , Camundongos Endogâmicos C3H , Hipófise/citologia , Células Piramidais/química , Fator de Transcrição Pit-1RESUMO
The origin and underlying mechanisms of hand preference are still unresolved, despite extensive research and discussion. Numerous possibilities have been considered, including genetic and hormonal factors, brain insult and learning. We suggest here that naturally occurring loss of axons of the corpus callosum (either symmetric or asymmetric, with or without neuron death) may be one mechanism underlying the embryological development of hand preference and hemispheric anatomical and functional asymmetries in males. We note supporting evidence for this hypothesis from a report of increased prevalence of left-handedness in children born prematurely at the gestational age prior to the likely onset of axon loss. The practical implications of this hypothesis for clinical management in neonatal intensive care units are discussed. It is suggested that the course of loss of callosal axons may have a genetic component which is associated with a sex-related influence and which is modifiable by prenatal and early postnatal events.
Assuntos
Axônios/fisiologia , Corpo Caloso/fisiologia , Lateralidade Funcional , Sobrevivência Celular , Corpo Caloso/citologia , Corpo Caloso/embriologia , Humanos , MasculinoAssuntos
Neocórtex/citologia , Neurônios/citologia , Animais , Biomarcadores , Encéfalo/citologia , Bromodesoxiuridina/metabolismo , Morte Celular , Divisão Celular , Movimento Celular , Reparo do DNA , Replicação do DNA , Imuno-Histoquímica , Macaca , Neocórtex/fisiologia , Neurônios/química , Neurônios/fisiologiaRESUMO
The use of an exogenously administered thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), for studies of the proliferation, migration and time of origin of cells in the cerebral cortex was investigated and compared with [3H]thymidine [( 3H]dT) autoradiography. Pregnant rats or mice were injected with BrdU and/or [3H]dT and processed by standard immunohistochemical techniques using a primary antibody directed against BrdU in single-stranded DNA, autoradiographic methods, or both. In animals that survived only 1 h after the injection, BrdU-positive cells were distributed in the proliferative zones throughout the central nervous system (CNS). In animals killed 1-3 days after the BrdU injection, intensely immunoreactive cells were in the superficial cortical plate and less intensely labeled cells were scattered throughout the deep cortical plate, the intermediate zone, and the germinal zones. In adult animals, 60 days or more after an injection of BrdU on GD 19, BrdU-positive cells were located in layer II/III of neocortex, the hippocampal pyramidal layer, and the granule layer of the dentate gyrus. In the double-labeling studies, the distribution of BrdU-immunoreactive cells was identical to that of autoradiographically labeled cells, and all autoradiographically labeled neurons were BrdU positive. Thus, BrdU immunohistochemistry is suitable for developmental studies of the CNS; moreover, it provides several advantages over [3H]dT autoradiography.
Assuntos
Encéfalo/embriologia , Bromodesoxiuridina , Imuno-Histoquímica/métodos , Animais , Autorradiografia , Encéfalo/citologia , Bromodesoxiuridina/administração & dosagem , Diferenciação Celular , Divisão Celular , Movimento Celular , Feminino , Camundongos , Gravidez , Ratos , Ratos Endogâmicos , Timidina , Fatores de TempoRESUMO
A simple growth algorithm is presented that deals with one feature of dendritic growth, the distance between branches. The fundamental assumption of our growth algorithm is that the lengths of dendritic segments are determined by the branching characteristics of the growing neurite. Realistic-appearing dendritic trees are produced by computer simulations in which it is assumed that: (1) growth of individual neurons occurs only at the tips of each growing neurite; (2) the growing neurite can either branch (as a bifurcation) or continue to elongate; (3) events at any one growing tip do not affect the events at any other growing tip; and (4) the probability of branching is a function only of the distance grown either from the cell body (if branching has not occurred) or from the previous branch point. An analytic solution of a differential equation based on these same assumptions produces a distribution of dendritic segment lengths that accurately fits an experimentally determined distribution of dendritic segment lengths of reconstructed neurons, accounting for about 89% of the sample variance. Our analysis indicates that, immediately following branching, the temporary suppression of further branching during dendritic growth may be an important mechanism for regulating the distance between branches.
Assuntos
Simulação por Computador , Dendritos/fisiologia , Modelos Neurológicos , Medula Espinal/fisiologia , Algoritmos , Animais , Transporte Axonal , Gatos , Dendritos/ultraestrutura , Peroxidase do Rábano Silvestre , Neurônios/citologia , Neurônios/fisiologia , Medula Espinal/ultraestrutura , Processos EstocásticosRESUMO
The distribution of acetylcholinesterase(AChE) in the hippocampal formation of the dreher mutant mouse was studied by comparing homozygous mutant (drsst-J/drsst-J) with littermate control (+/? or +/+). In the control mice, AChE activity was most intense in the inner one-third of the stratum oriens and lacnosum of the hippocampus, and in the inner one-fifth of the molecular layer of the dentate gyrus. In contrast, in homozygous dreher mice, AChE activity in area CA3c of the hippocampus was not restricted to the stratum oriens, and extended upward into the infrapyramidal and suprapyramidal mossy fiber layers, the lower part of the stratum radiatum, the pyramidal cell layer, and downward toward the alveus. In addition, the distribution of AChE activity was modified by accompanying with ectopic pyramidal cells or with disruption of the pyramidal cell layer. AChE activity in the dentate gyrus of the dreher mouse was not confined to the inner one-fifth of the molecular layer. These findings indicated that the cholinergic input to the hippocampal formation is not normal in the dreher mutant mouse. Since the areas of AChE activity correspond to the presence of ectopic pyramidal cells in the dreher mouse, incoming cholinergic fibers may form synapses with these ectopic cells and with the dendrites of normal pyramidal cells that extend into the expanded area of AChE activity.
Assuntos
Acetilcolinesterase/metabolismo , Hipocampo/enzimologia , Células Piramidais/fisiologia , Animais , Feminino , Homozigoto , Masculino , Camundongos , Camundongos MutantesRESUMO
The lamination of the hippocampus in the homozygous B6CBA weaver mouse (wv/wv) was compared with that in normal B6CBA littermates (+/+) and C57BL/6J mice using Nissl and Timm's staining. In Nissl-stained preparations, the normal littermates exhibit a compact, regular arrangement of pyramidal cells in area CA3 of the hippocampus. In contrast, in homozygous weaver mutant mice, the pyramidal cell layer of area CA3 frequently appears to be thicker than normal with an apparent increase of neuropil, as evidenced by the presence of cell-free spaces within the layer. Also, small ectopic clusters of pyramidal cells and sometimes the subdivision of the pyramidal cell layer into 2 or 3 layers were found throughout the dorsoventral extent of the hippocampus. In Timm's stained preparations of the normal mouse hippocampus, two clearly separated bundles of axons were seen emerging from the hilus: one bundle running above the pyramidal cell layer of area CA3 (i.e., the suprapyramidal mossy fiber layer, SPMFL), and the second bundle running below the pyramidal cell layer (i.e., the infrapyramidal mossy fiber layer, IPMFL). In contrast, in some homozygous weaver mice, the origin of the mossy fiber bundles is clearly different from normal; specifically, mossy fibers emerge in a diffuse fashion from the area between suprapyramidal and infrapyramidal mossy fiber layers. In other weaver mice, short, discontinuous bundles diverge from the infrapyramidal mossy fiber layer and invade the thickened pyramidal cell layer. In addition, ectopic pyramidal cells are situated below the IPMFL in area CA3. The morphological changes observed in hippocampus of weaver mutants are likely to be secondary to a more basic genetic defect.
Assuntos
Hipocampo/patologia , Animais , Axônios/fisiologia , Axônios/ultraestrutura , Corantes , Hipocampo/citologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Camundongos Mutantes Neurológicos , Fibras Nervosas/fisiologia , Fibras Nervosas/ultraestrutura , Células Piramidais/fisiologia , Células Piramidais/ultraestruturaRESUMO
Neuropathological changes in the cerebellar cortex of microsphere-embolized rats were studied at 30 min and 3 h after the embolism. Necrotic processes including a sponge-like vacuolation in the molecular layer, a vague outline of some Purkinje cells, and a few pyknotic granule cells having small and dark profiles were identified at sometime between 30 min and 3 h after microsphere-induced embolism in Nissl staining. Glial fibrillary acidic protein staining shows an apparent reduction in the number of Bergmann glial processes in some of the areas where there was necrosis of the molecular layer and poor astroglia processes in the areas subjacent to the pyknotic granule cells. These data demonstrate that within a short time, microsphere-induced cerebral ischemia produces necrosis of cerebellar neurons (i.e. Purkinje and granule cells) and changes in cerebellar glia cells (i.e. Bergmann and astroglia cells), and that these neuropathological changes are secondary phenomenon caused by microsphere blockage of cerebellar blood flow.
Assuntos
Cerebelo/patologia , Embolia Intracraniana/patologia , Neuroglia/patologia , Neurônios/patologia , Animais , Cerebelo/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Embolia Intracraniana/induzido quimicamente , Embolia Intracraniana/metabolismo , Masculino , Microesferas , Neuroglia/metabolismo , Neurônios/metabolismo , Ratos , Ratos Wistar , Fatores de TempoRESUMO
The output potential of proliferating populations in either the developing or the adult nervous system is critically dependent on the length of the cell cycle (T(c)) and the size of the proliferating population. We developed a new approach for analyzing the cell cycle, the 'Saturate and Survive Method' (SSM), that also reveals the dynamic behaviors in the proliferative population and estimates of the size of the proliferating population. We used this method to analyze the proliferating population of the adult dentate gyrus in 60 day old mice of two inbred strains, C57BL/6J and BALB/cByJ. The results show that the number of cells labeled by exposure to BUdR changes dramatically with time as a function of the number of proliferating cells in the population, the length of the S-phase, cell division, the length of the cell cycle, dilution of the S-phase label, and cell death. The major difference between C57BL/6J and BALB/cByJ mice is the size of the proliferating population, which differs by a factor of two; the lengths of the cell cycle and the S-phase and the probability that a newly produced cell will die within the first 10 days do not differ in these two strains. This indicates that genetic regulation of the size of the proliferating population is independent of the genetic regulation of cell death among those newly produced cells. The dynamic changes in the number of labeled cells as revealed by the SSM protocol also indicate that neither single nor repeated daily injections of BUdR accurately measure 'proliferation.'
Assuntos
Giro Denteado/citologia , Camundongos Endogâmicos BALB C/anatomia & histologia , Camundongos Endogâmicos C57BL/anatomia & histologia , Neuroglia/citologia , Neurônios/citologia , Animais , Contagem de Células , Divisão Celular/fisiologia , Camundongos , Fase S , Fatores de TempoRESUMO
To analyze developmental abnormalities related to neural migration in the NZB/BINJ mouse, the pattern of cerebellar foliation and neural position were compared with that of a normal mouse (C57BL/6J). Three abnormalities of cerebellar foliation--(1) lobe isolated from other cerebellar lobes, (2) lobes imbalanced in relative amounts or ratio of granular cell layer and molecular layer, (3) lobes in which some Purkinje cells and the molecular layer was embedded in the granular cell layer--were observed in NZB/BINJ mice. These morphological abnormalities were not limited to a specific lobe. On the other hand, abnormalities of neural position were observed in both granule and Purkinje cells. The pattern of ectopically-situated granule cells, in general, could be divided into 3 types: (1) large cell clusters extending from granular cell layer to the pia mater or middle part of the molecular layer, (2) clusters of various sizes scattered within the white matter and (3) clusters formed by combination of granule cells extending from two opposed granular cell layers to the molecular layer. The pattern of ectopically-situated Purkinje cells could be divided into 4 types: (1) ectopia of a group of cells from one part of the Purkinje cell layer, (2) ectopia of a single Purkinje cell observed in the molecular layer, (3) single Purkinje cell scattered within the white matter accompanied by clusters of ectopic granule cells and (4) ectopic Purkinje cells embedded in the granular cell layer. The abnormalities in position of both granule cells and Purkinje cells was not limited to a particular cerebellar lobe.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cerebelo/citologia , Camundongos Endogâmicos NZB/anatomia & histologia , Camundongos Mutantes Neurológicos/anatomia & histologia , Neurônios/citologia , Animais , Granulócitos/citologia , Camundongos , Camundongos Endogâmicos C57BL , Células de Purkinje/citologiaRESUMO
The laminated structures in the hippocampal formation and cerebellum of homozygous dreher mice were compared to their littermates and to C57BL/6J mice in Nissl- and myelin-stained preparations. In the dreher dentate gyrus, ectopic granule cells were situated in the molecular layer, and frequently there was either partial or complete absence of the infrapyramidal limb of the granule cell layer. In the dreher hippocampus, the cells of the pyramidal cell layer in area CA3 formed widely dispersed arrangements, and there were ectopically situated pyramidal cells in the stratum radiatum and stratum oriens. In the dreher cerebellum, 3 abnormal patterns were observed: (1) disruptions of foliation with normal cytoarchitectonic structure, (2) foliation with a mixture of normal laminated structure and abnormal laminated structure, and (3) almost complete absence of the cerebellum. In abnormal folia exhibiting the second or third pattern, islands consisting of agglomerations of both granule cells and Purkinje cells or just granule cells were observed. The neuronal heterotopias and cytoarchitectonic disorganization observed in the present study are apparently secondary to disruption of cell proliferation and neuronal migration produced directly or indirectly by the dreher mutation. In addition, the fact that the phenotypic abnormalities in homozygous dreher mice produces different abnormal morphologies in different specimens may be useful for analyzing the development of the hippocampal formation and cerebellum.
Assuntos
Cerebelo/anormalidades , Cerebelo/ultraestrutura , Hipocampo/anormalidades , Hipocampo/ultraestrutura , Animais , Genótipo , Camundongos , Camundongos Mutantes NeurológicosRESUMO
The organization of pyramidal cells and mossy fibers in the hippocampal formation of homozygous dreher(J) mutant mice was investigated using Timm's and Golgi methods. Five clear abnormalities were found: (1) some pyramidal cells were located below the infrapyramidal mossy fiber layer, (2) mossy fibers emerged in diffuse fashion from between the suprapyramidal and infrapyramidal mossy fiber layers, and their fibers invaded within the pyramidal cell layer, where they traveled as 3-6 small, usually quite short, bundles, (3) some normally situated pyramidal cells had unusual contacts with mossy fibers at two or three places on their apical and/or basal dendrites, (4) some normally situated pyramidal cells had abnormal dendritic trees typified by the occurrence of fine-caliber dendritic branches extending out of the apical dendrite or the apical portion of the soma, and (5) a few Timm positive fibers extending from the dentate hilus to the dentate molecular layer in both dreher(J) and control mice were observed. These abnormalities indicate that in the hippocampal formation a variety of cell populations and neuronal circuits can be indirectly modified by the dreher mutation.