RESUMEN

Age-related brain changes are widely documented. Because of differences in measurement methods and case selection, the reported effects of age on regional grey and white matter brain volumes, however, are much more pronounced and widespread in neuroimaging than in postmortem studies. Consequently, the magnitude of the effect that is specific to chronological age remains unresolved. We present postmortem volume measurements for 26 cortical, subcortical and white matter regions, in 24 human brains aged 46-92 years, free of neuropathological abnormalities. Significant age-related loss was observed in anterior and posterior white matter but not in total grey matter volumes. Further analyses on five cortical subregions previously reported to exhibit large age-related loss on MRI yielded negative results. These analyses demonstrate smaller changes with age than those reported in imaging studies. Although this discrepancy between postmortem and imaging studies may partly be explained by the increase in noise of the neuroimaging data with age, our results suggest that healthy brain ageing is a process affecting predominantly white matter not grey matter.

Asunto(s)

Envejecimiento/patología , Encéfalo/patología , Fibras Nerviosas Mielínicas/patología , Neuronas/patología , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Femenino , Lateralidad Funcional , Humanos , Modelos Lineales , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Análisis de Regresión , Caracteres Sexuales

RESUMEN

Tardive dyskinesia (TD) is relatively common among psychiatric patients on maintenance therapy with typical neuroleptics and persists in more than 20% even after withdrawal of the medication. Such persistence suggests an underlying pathology due to neurotoxicity. We present evidence for such a neurotoxic mechanism in a baboon model of TD. Four baboons were treated chronically with the dehydration product of haloperidol, 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-1,2,3,6- tetrahydropyridine (HPTP), which is metabolized, similarly to haloperidol, to two neurotoxic pyridinium species. The animals developed orofacial dyskinesia which persisted after HPTP was ceased. Serial sections of the entire brain from the four treated animals and four vehicle-treated controls revealed volume loss in the basal forebrain and hypothalamus. Histological evaluation demonstrated a reduction in the density of magnocellular neurons in the anterior region of the nucleus basalis of Meynert (NbM). We speculate that the loss of these NbM neurons may be associated with the persistent orofacial dyskinesia observed in the HPTP-treated animals. These findings may contribute to a better understanding of neuroleptic-induced TD.

Asunto(s)

Antipsicóticos/efectos adversos , Discinesia Inducida por Medicamentos/etiología , Haloperidol/análogos & derivados , Hipotálamo/efectos de los fármacos , Prosencéfalo/efectos de los fármacos , Animales , Discinesia Inducida por Medicamentos/fisiopatología , Músculos Faciales/fisiopatología , Haloperidol/efectos adversos , Hipotálamo/patología , Masculino , Neuronas/efectos de los fármacos , Neuronas/patología , Papio , Prosencéfalo/patología

RESUMEN

The present study analyzes the relationship between cortical and subcortical brain volumes in patients with Huntington's disease. The brains of seven patients with a clinical diagnosis and positive family history of Huntington's disease and 12 controls were collected at autopsy with consent from relatives. Detailed clinical assessments were available for all study subjects with genotype confirmation for patients with Huntington's disease. Volume analysis of the brain on serial 3-mm coronal slices was performed as previously described. All patients with Huntington's disease exhibited significant brain atrophy resulting from volume reductions in both cortical and subcortical grey matter. Atrophy of the cortex was relatively uniform, although the medial temporal lobe structures were spared. The caudate nucleus and putamen were strikingly reduced in all cases and this atrophy correlated with the severity of cortical atrophy, suggesting an associated disease process. The rate of cortical but not subcortical atrophy correlated with CAG repeat numbers. Loss of frontal white matter correlated with both cortical and striatal atrophy. Age of onset of chorea correlated with the amount of subcortical atrophy, while duration of chorea correlated negatively with atrophy of the white matter. These results suggest a more widespread and global disease process in patients with Huntington's disease.

Asunto(s)

Ganglios Basales/patología , Encefalopatías/patología , Corteza Cerebral/patología , Enfermedad de Huntington/patología , Adulto , Anciano , Atrofia , Encefalopatías/genética , Salud de la Familia , Femenino , Humanos , Enfermedad de Huntington/genética , Masculino , Persona de Mediana Edad

RESUMEN

The present study evaluates the cytoarchitecture of midbrain dopaminergic regions in baboons using similar methodology to that recently applied to compare humans and rats. This information is relevant for the interpretation of nonhuman primate models of Parkinson's disease (PD). The midbrains of four alpha male baboons were serially sectioned into 10 evenly spaced series of 50 microm sections. Series were stained with either cresyl violet or immunohistochemically reacted for tyrosine hydroxylase, substance P, calbindin-D28k, or parvalbumin. The organization of dopaminergic cell groups and the distribution of proteins within these groups were found to be very similar to that previously described in humans [McRitchie et al., J. Comp. Neurol. 364:121-150; 1996]. Dorsal and ventral tiers of the A9 substantia nigra (SN) pars compacta and all divisions of the A8 and A10 cell groups were identified revealing a high degree of homology in the arrangement of chemically distinct midbrain neurons between primates. The major difference between the organization of human and baboon midbrain dopaminergic neurons is the anteroposterior extent of the dense cell clusters within the SN pars compacta. In baboons the dorsomedial cell cluster is absent at posterior levels. The ventral tier cell clusters, which are targeted by PD in humans, are restricted to the posterior and ventral regions of the SN pars compacta of the baboon. In humans these cell clusters are found throughout the rostrocaudal extent of the SN. These ventral cell clusters have been previously shown to have reciprocal connections with sensorimotor regions of the putamen.

Asunto(s)

Dopamina/fisiología , Neuronas/química , Papio/anatomía & histología , Sustancia Negra/citología , Área Tegmental Ventral/citología , Animales , Proteínas de Unión al Calcio/fisiología , Tamaño de la Célula/fisiología , Humanos , Masculino , Vías Nerviosas , Neuronas/citología , Neuronas/enzimología , Enfermedad de Parkinson Secundaria/fisiopatología , Sustancia Negra/química , Sustancia Negra/fisiología , Tirosina 3-Monooxigenasa/análisis , Área Tegmental Ventral/química , Área Tegmental Ventral/fisiología

RESUMEN

We have analyzed the neuropathology of the substantia nigra in four cases of progressive supranuclear palsy compared with age-matched controls and patients with Parkinson's disease. Although there are many reports of severe dopaminergic cell loss in progressive supranuclear palsy, the fate of the GABAergic pars reticulata neurones remains unclear. Serial section analysis and fractional counts of pars compacta neurones (identified by their neuromelanin pigment) and pars reticulata neurones (identified using parvalbumin immunohistochemistry) were performed, and the type and distribution of neuropathology were described. Severe neurodegeneration within the dopaminergic pars compacta was seen in all cases of progressive supranuclear palsy and all cases of Parkinson's disease compared with controls. Lewy body pathology was found only in cases of Parkinson's disease, while neurofibrillary tangles were seen only in cases of progressive supranuclear palsy. Tau-positive astrocytes and neuropil threads were occasionally seen in controls and cases of Parkinson's disease (particularly those of advanced age) but were extremely numerous in all cases of progressive supranuclear palsy. There was a similar decrease in parvalbumin immunoreactivity within the pars reticulata in both progressive supranuclear palsy and Parkinson's disease. However, there was a striking 70% reduction in the number of pars reticulata neurones in progressive supranuclear palsy, with no cell loss observed in Parkinson's disease compared with controls. Our results show that both the dopaminergic pars compacta and the GABAergic pars reticulata are significantly damaged in cases of progressive supranuclear palsy. The distribution of neurodegeneration in patients with Parkinson's disease and progressive supranuclear palsy is discussed with respect to the current theories on pathophysiology in basal ganglia circuitry.

Asunto(s)

Sustancia Negra/patología , Parálisis Supranuclear Progresiva/patología , Anciano , Anciano de 80 o más Años , Recuento de Células , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Degeneración Nerviosa , Red Nerviosa/ultraestructura , Ovillos Neurofibrilares/patología , Neuronas/patología , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Parvalbúminas/metabolismo , Valores de Referencia , Sustancia Negra/metabolismo , Parálisis Supranuclear Progresiva/metabolismo , Proteínas tau/metabolismo

RESUMEN

Using unbiased quantitative techniques, we evaluated the effect of Parkinson's disease on the regional size and the number of tyrosine hydroxylase-producing neurons and all neurons in the midbrain A8 and A10 dopaminergic cell groups located adjacent to the substantia nigra. Seven patients with Lewy body Parkinson's disease were evaluated and compared with five controls. Four of the patients with Parkinson's disease had additional neuropathology, and the effect of concomitant pathology on A10 populations was also determined. Degeneration was not observed in the A8 regions of any patient, and only certain A10 nuclei were affected by the disease. The parabrachial pigmented nucleus situated dorsal to the substantial nigra, and the parapeduncular nucleus located rostromedially were significantly reduced by 40-50% in patients with Parkinson's disease. Few differences were found between patients with or without additional pathology, suggesting a similar pathogenic mechanism to that observed in the substantia nigra of these patients. However, patients with additional pathology also had serotonergic cell loss in the caudal linear nucleus. There was a reduction in tyrosine hydroxylase immunoreactivity but no overt neurodegeneration in other A10 regions, suggesting the disease may also influence the production of dopamine in some surviving neurons.

Asunto(s)

Dopamina/metabolismo , Mesencéfalo/metabolismo , Mesencéfalo/patología , Degeneración Nerviosa , Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Anciano , Anciano de 80 o más Años , Encefalopatías/complicaciones , Muerte Celular , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neuronas/metabolismo , Enfermedad de Parkinson/complicaciones , Valores de Referencia , Serotonina/metabolismo , Tirosina 3-Monooxigenasa/metabolismo

RESUMEN

The subthalamus has become a promising target for the neurosurgical treatment of parkinsonian symptoms. We have used unbiased counting techniques to quantify the neuronal populations of the subthalamic nucleus in patients with idiopathic Parkinson's disease and progressive supranuclear palsy. In addition, the type of calcium binding proteins contained within these subthalamic neurons was established using immunohistochemistry. Most of the 550,000 subthalamic neurons contain either parvalbumin or calretinin calcium binding proteins, and patients with idiopathic Parkinson's disease sustained no damage to this nucleus. This is consistent with current theories of basal ganglia circuitry, which postulate that overstimulation of this excitatory nucleus contributes to the inhibition of the motor thalamus via the activation of inhibitory relays. In contrast, we found that there was substantial cell loss in the subthalamus in progressive supranuclear palsy (45 to 85% neuronal reduction) and that both cell types were equally affected. Extracellular neurofibrillary tangles as well as tau-positive glia were observed in the subthalamus of these cases. As the patients with Parkinson's disease and progressive supranuclear palsy all had overlapping parkinsonian symptoms, the loss of subthalamic stimulation within the basal ganglia of progressive supranuclear palsy cases is puzzling, unless their parkinsonian symptoms were generated by an alternate mechanism.

Asunto(s)

Enfermedad de Parkinson/metabolismo , Enfermedad de Parkinson/patología , Parálisis Supranuclear Progresiva/metabolismo , Parálisis Supranuclear Progresiva/patología , Núcleos Talámicos/metabolismo , Núcleos Talámicos/patología , Anciano , Anciano de 80 o más Años , Calbindina 2 , Calbindinas , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Parvalbúminas/metabolismo , Proteína G de Unión al Calcio S100/metabolismo , Proteínas tau/metabolismo

RESUMEN

BACKGROUND: Many studies have demonstrated significant sexual dimorphism in verbal ability. However, few studies have examined anatomical differences between the sexes that may underlie such dimorphism. OBJECTIVE: To examine sex differences in the absolute and proportional volumes of the main language-associated regions of the cerebral cortex. DESIGN AND MAIN OUTCOME MEASURES: Control neuropathological case series of consecutive autopsies from a teaching hospital. No significant age-related volume changes were identified in the sample. Two language-associated cortical regions, the superior temporal gyrus (part of the Wernicke area) and its subdivisions (planum temporale, Heschl gyrus, and anterior superior temporal gyrus) and the inferior frontal gyrus (Broca area in the dominant hemisphere), and a non-language-associated region, the frontal pole, were measured using stereological techniques in brains fixed with formaldehyde solution serially sectioned at 3-mm intervals. Volume comparisons between the sexes and between brain hemispheres were performed using 2-way analysis of variance. SETTING: Studies were conducted at the University of Sydney and the Prince of Wales Medical Research Institute, Sydney, Australia. PATIENTS: Ten males and 11 females free from neurologic or neuropathological abnormalities. RESULTS: The volume of the superior temporal cortex, expressed as a proportion of total cerebral volume, was significantly larger in females compared with males (17.8% increase; P = .04). This was accounted for by 1 section of the superior temporal cortex, the planum temporale, which was 29.8% larger in females (P = .04). In addition, the cortical volume fraction of the Broca area in females was 20.4% larger than in males (P = .05). In contrast, no significant differences were found in the proportional volume of the frontal pole or in regional volumes between the left and right hemispheres in either sex group. CONCLUSIONS: Our results suggest that females have proportionally larger Wernicke and Broca language-associated regions compared with males. These anatomical differences may correlate with superior language skills previously demonstrated in females.

Asunto(s)

Corteza Cerebral/anatomía & histología , Lenguaje , Caracteres Sexuales , Anciano , Anciano de 80 o más Años , Cadáver , Corteza Cerebral/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad

RESUMEN

This study measured brain atrophy in patients with idiopathic Parkinson's disease and diffuse Lewy body disease, all of whom had equivalent loss of midbrain dopammergic neurons and absence of Alzheimer's disease. Characteristic patterns of volume loss were found throughout the brain, depending on the age of onset and clinical signs. An equivalent loss of medial temporal lobe structures occurred in all parkinsonian patients. This atrophy was similar in magnitude to that seen in Alzheimer's disease and is likely to be the anatomical substrate for the memory deficits found in each of these patients groups. Frontal lobe atrophy was a feature of both late-onset Parkinson's disease (mild atrophy) and diffuse Lewy body disease (significant atrophy) groups, with all cases analyzed having dementia. Atrophy of frontal lobes correlated with the duration of motor symptoms in these patients and may suggest an association between dopammergic deafferentation, frontal atrophy and dementia.

Asunto(s)

Encéfalo/patología , Enfermedad de Parkinson/patología , Anciano , Anciano de 80 o más Años , Atrofia , Femenino , Lóbulo Frontal/patología , Humanos , Masculino , Persona de Mediana Edad , Movimiento , Tamaño de los Órganos , Enfermedad de Parkinson/fisiopatología , Valores de Referencia , Lóbulo Temporal/patología

RESUMEN

An improved method for the histopathological evaluation of the substantia nigra for diagnostic purposes is proposed. This method takes advantage of the natural architecture of the constituent cell clusters of the substantia nigra by combining standardized sections in the horizontal plane and simple quantification. The use of this standardized technique should increase the diagnostic reliability and sensitivity of patterns of cell loss within the substantia nigra.

Asunto(s)

Enfermedad de Parkinson/diagnóstico , Patología/métodos , Sustancia Negra/patología , Tronco Encefálico/anatomía & histología , Tronco Encefálico/patología , Humanos , Enfermedad de Parkinson/patología

RESUMEN

OBJECTIVE: To further elucidate the relation between diffuse Lewy body disease and Parkinson's disease. METHODS AND RESULTS: The clinical features of nine cases of pure diffuse Lewy body disease without pathological evidence of coexisting Alzheimer's neuritic pathology were reported. All patients were aged less than 70 years at onset (mean 62 years). Five patients presented with clinical features, which included assymetric resting tremor had levodopa responsiveness, which were initially indistinguishable from idiopathic Parkinson's disease. All five patients later became demented (mean of three years after presentation). Two further patients presented with parkinsonism and dementia and two patients presented with dementia and developed parkinsonism at a later stage. Hallucinations appeared 2.5-9 years after the onset of symptoms in six patients and were a presenting feature in one patient. All patients met the pathological criteria of idiopathic Parkinson's disease, with respect to the midbrain changes, in addition to having diffuse cortical Lewy bodies. CONCLUSIONS: Diffuse Lewy body disease may present a parkinsonism, dementia, or both depending on whether the Lewy body pathology begins in the midbrain, the cortex, or both together. When it begins in the midbrain, diffuse Lewy body disease is indistinguishable initially from idiopathic Parkinson's disease. Diffuse Lewy body disease may be a common cause of dementia complicating Parkinson's disease.

Asunto(s)

Enfermedad de Alzheimer/patología , Enfermedad de Parkinson/patología , Anciano , Enfermedad de Alzheimer/psicología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/psicología

RESUMEN

We have examined by immunohistochemistry the parvalbumin-containing neurons of the substantia nigra in patients with Parkinson's disease and in age-matched controls. Parvalbumin, a calcium binding protein, is involved in buffering intracellular calcium and in this study was localized within the majority of non-pigmented neurons of the human pars reticulata. Previous studies have shown that the parvalbumin-immunoreactive pars reticulata neurons are GABAergic and project to the motor thalamus and tectum. Their increased output, due to the loss of dopaminergic inhibition in Parkinson's disease, decreases cortical activation via thalamic pathways, causing parkinsonian symptoms. In Parkinson's disease there was a significant loss of parvalbumin-immunoreactivity from these neurons, though there was no evidence of actual cell loss. This loss of parvalbumin-immunoreactivity was detected only in those cases with end-stage Parkinson's disease.

Asunto(s)

Neuronas/patología , Enfermedad de Parkinson/patología , Parvalbúminas/análisis , Sustancia Negra/patología , Edad de Inicio , Anciano , Anciano de 80 o más Años , Causas de Muerte , Femenino , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Enfermedad de Parkinson/fisiopatología , Valores de Referencia , Ácido gamma-Aminobutírico/análisis

RESUMEN

We have quantified midbrain cell loss in idiopathic Parkinson's disease (PD) compared with controls; six patients had PD with onset before 70 years, five patients had late onset PD (>70 years) and nine patients had diffuse Lewy body disease. The pattern of cell loss in these last two groups has not been previously described. No age associated neuronal loss was seen in controls. There was cell loss and reduced area of the pars compacta in all cases but no difference in the pattern of cell loss, which was predominantly ventral. The amount of cell loss in the dorsolateral cluster correlated with the duration of Parkinsonian symptoms, while greater cell loss in the dorsomedial cluster correlated with the presence of tremor and the absence of early dementia. These results suggest that the topography of midbrain pathology does not assist in differentiating these overlapping syndromes.

RESUMEN

The present study compares the distribution of three calcium binding proteins, calbindin-D28k, calretinin, and parvalbumin, in the midbrain tegmentum of rats and humans. In order to compare the distributions of these proteins directly, the cytoarchitecture of this region was evaluated by using immunohistochemistry for tyrosine hydroxylase and substance P in serial sections in both transverse and horizontal planes. There was a high degree of homology in the cytoarchitecture of the three main dopaminergic regions identified. The A8 group was localised in the retrorubral fields, which extended rostrally into the midbrain reticular fields in the human. The A9 group corresponded to the substantia nigra, which was delimited by its dense substance P innervation. The heterogeneous A10 group, situated along the dorsal border as well as medial to the A9 group, comprised multiple nuclei. The distribution of calcium binding proteins was similar in both species, although a larger proportion of neurons contained these proteins in the rat. Calbindin-D28k was localised in neurons within A8 and A10 nuclei and within the caudomedial A9 region (and rostrolateral A9 in the rat only). Calretinin was localised in similar regions. In contrast, neurons containing parvalbumin were concentrated in the substantia nigra pars reticulata. The results suggest that few dopaminergic neurons receiving striatal input in the substantia nigra contain calcium binding proteins; rather, the nondopaminergic nigral neurons contain parvalbumin. Interestingly, dopaminergic neurons are more numerous in humans, whereas nondopaminergic neurons predominate in rats, which suggests that functional differences may exist between rats and humans.

Asunto(s)

Proteínas de Unión al Calcio/análisis , Mesencéfalo/química , Ratas Wistar/fisiología , Adulto , Anciano , Anciano de 80 o más Años , Animales , Especificidad de Anticuerpos , Calbindina 1 , Calbindina 2 , Calbindinas , Dopamina/fisiología , Femenino , Humanos , Inmunohistoquímica , Masculino , Mesencéfalo/citología , Persona de Mediana Edad , Proteínas del Tejido Nervioso/análisis , Proteínas del Tejido Nervioso/inmunología , Neuronas/química , Parvalbúminas/análisis , Parvalbúminas/inmunología , Ratas , Formación Reticular/química , Formación Reticular/citología , Proteína G de Unión al Calcio S100/análisis , Proteína G de Unión al Calcio S100/inmunología , Sustancia Negra/química , Sustancia Negra/citología , Tegmento Mesencefálico/química , Tegmento Mesencefálico/citología

RESUMEN

The physiological characteristics of central neural populations are being increasingly explored in slice preparations. A major challenge of this approach is to correlate the physiological properties of individual neurones or groups of neurones with their anatomical and chemical properties in order to gain key insights into their functional identities. The present study describes a method for determining the precise topographical position and the immunohistochemical characteristics of neurones in brain slice preparations that are used frequently in electrophysiological investigations. Thick horizontal slices of rat brainstem were re-cut using a method that provided thin sections that were always in the same plane as the parent slice and that were of suitable thickness for immunohistochemistry. Catecholaminergic neurones in these co-planar (horizontal) sections were stained using antisera to tyrosine hydroxylase, the rate-limiting enzyme for catecholamine synthesis. To identify individual catecholamine neurones in the co-planar sections, we constructed a reference atlas of the distribution of catecholamine neurones in the horizontal plane of the rat brain. The combined use of the horizontal atlas and of immunohistochemical techniques in co-planar sections of horizontal slices enables the determination of several key properties: (1) whether a neurone is TH-positive, (2) its precise topographical position and (3) its content of neuropeptides and other immunohistochemical markers. Thus our study offers a readily feasible method for correlative anatomy and immunohistochemistry of physiologically identified catecholaminergic neurones in brain slices.

Asunto(s)

Encéfalo/anatomía & histología , Encéfalo/fisiología , Catecolaminas/metabolismo , Neuronas/metabolismo , Animales , Encéfalo/citología , Electrofisiología , Femenino , Inmunohistoquímica , Técnicas In Vitro , Ratas , Ratas Sprague-Dawley , Distribución Tisular , Tirosina 3-Monooxigenasa/metabolismo

RESUMEN

At present there is no consensus concerning the internal organization of the human substantia nigra, despite its pivotal role in neurodegenerative conditions. We have quantitatively analysed the variability in the pattern of clusters of melanin-pigmented neurons in the human substantia nigra using serial section analysis and computer reconstructions. The substantia nigra pars compacta showed a bilaminar organization consisting of the pars medialis and pars lateralis, as well as dorsal and ventral tiers as described previously [D. A. McRitchie et al. (1995) J. comp. Neurol. (in press)]. Both the dorsal and ventral tiers could be further subdivided into three mediolateral cell columns based on position and cell density. The presence and arrangement of these cell clusters was most variable in transverse sections (the plane currently used for diagnostic neuropathology). Quantitative assessment of the topographical pattern of cell loss within single transverse sections of the human substantia nigra should therefore be treated with some caution. In contrast, the full rostrocaudal extent of the cell columns could be seen in horizontal sections. Thus, consistent samples of larger numbers of pigmented neurons per region were found in this section plane, although only two cell columns were found in most sections. Our results show that greater quantitative reliability can be achieved with horizontal sections of the substantia nigra.

Asunto(s)

Sustancia Negra/citología , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Células , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Melaninas/metabolismo , Persona de Mediana Edad , Pigmentación

RESUMEN

A controversy exists in the literature as to whether neurons containing the calcium binding protein calbindin-D28k are located within the human substantia nigra. The point of variance between reports, however, is not the anatomical distribution of these neurons, but rather the delineation of the dorsal border of the substantia nigra. It has been suggested that the dense substance P striatonigral innervation delimits the substantia nigra in the human. The aim of the present study is to re-examine the distribution of calbindin-D28k-positive neurons throughout the substantia nigra using substance P to delimit its borders. Although a few calbindin-D28k-positive neurons were found in the medial cell group of the substantia nigra, the vast majority of positive neurons were located in the adjacent A8 and A10 dopaminergic cell groups. This anatomical location of calbindin-D28k-positive neurons is consistent with previous reports, though our results indicate that when the striatonigral projection is used to define the substantia nigra, calbindin-D28k is not a notable feature of these neurons. This questions the neuroprotective role of this protein in Parkinson's disease.

Asunto(s)

Proteínas de Unión al Calcio/fisiología , Neuronas/fisiología , Sustancia Negra/fisiología , Adulto , Anciano , Autopsia , Femenino , Humanos , Inmunohistoquímica , Masculino , Mesencéfalo , Persona de Mediana Edad , Sustancia P/inmunología

RESUMEN

A 66-year-old woman presented with an alien limb syndrome without dementia. The course of her illness was unremitting and at autopsy 6 years later her diagnosis was confirmed as corticobasal degeneration without Alzheimer-type pathology. Although the presence of ballooned achromatic cortical neurons and cell loss from the substantia nigra distinguishes such patients, the site and density of achromatic neurons has not previously been quantified. We show that immunohistochemistry for the cell stress protein ubiquitin selectively stains these achromatic neurons, whereas they do not stain for abnormally phosphorylated tau protein. Phosphorylated neurofilament antibodies recognise both ballooned and non-ballooned neurons. In this case, high densities of ubiquitin-positive ballooned neurons were found in frontal cortical regions with the highest densities in layers V and VI of the anterior cingulate cortex. In addition, high densities of ubiquitin-positive ballooned neurons were found in the insular cortex, claustrum and amygdala. These results confirm past reports of frontal pathology, but show that there is also considerable pathology in insular and parahippocampal cortical regions and some subcortical regions. Our findings suggest that the distribution and staining characteristics of ballooned neurons in corticobasal degeneration may help to differentiate these cases pathologically, while the absence of dementia appears to be an important clinical criterion.

Asunto(s)

Corteza Cerebral/patología , Neuronas/ultraestructura , Ubiquitinas/metabolismo , Anciano , Enfermedad de Alzheimer , Autopsia , Demencia , Femenino , Humanos , Degeneración Nerviosa , Factores de Tiempo , Distribución Tisular

RESUMEN

The anatomical distribution of substance P-like immunoreactivity across the subnuclear divisions of the nucleus of the solitary tract has been examined in the human medulla oblongata. A differential distribution of neurons, fibres, and terminals was observed throughout the ten subnuclear divisions of this nucleus. Substance P-like immunoreactive neurons were observed most frequently in the nucleus gelatinosus, with moderate numbers in the medial, intermediate subnuclei and very few in the commissural, ventral, dorsal, and dorsolateral subnuclei. The paracommissural, ventrolateral, and interstitial subnuclei did not contain substance P-like-immunoreactive neurons. These neurons were typically bipolar and moderate-sized to large, except for the neurons in the nucleus gelatinosus, which were substantially smaller. The highest densities of fibres and terminals were observed in the gelatinosus, medial, and intermediate nuclei, with moderate densities in the paracommissural and dorsal subnuclei. Sparse substance P-like-immunoreactive fibres and terminals were seen in the ventral and interstitial nuclei as well as within the solitary tract. The dorsolateral nucleus was characterized by a light distribution of fibres and terminals, except for a dense aggregation along its lateralmost border. A prominent innervation of pigmented neurons by substance P-like-immunoreactive terminals and fibres was also observed in the dorsolateral nucleus. The results reveal that the subnuclear complexity of the nucleus of the solitary tract is richly reflected by its differential pattern of substance P-like-immunoreactive structures.

Asunto(s)

Bulbo Raquídeo/metabolismo , Terminaciones Nerviosas/metabolismo , Neuronas/metabolismo , Sustancia P/metabolismo , Anciano , Tronco Encefálico , Femenino , Humanos , Inmunohistoquímica , Masculino , Bulbo Raquídeo/citología , Persona de Mediana Edad , Distribución Tisular

RESUMEN

The present study examines the topography and cytoarchitecture of the solitary nucleus (Sol). Three human medulla oblongatae were serially sectioned and alternate sections were reacted for the enzyme acetylcholinesterase or stained with cresyl violet. The 10 component subnuclei of Sol were identified on the basis of their acetylcholinesterase reactivity and cytoarchitecture. These subnuclei are the paracommissural, commissural, gelatinosus, medial, ventral, ventrolateral, dorsal, dorsolateral, intermediate, and interstitial. Cytoarchitecturally, Sol is characterised by an abundance of small cells of varied morphology but also features some medium to large cells as well as pigmented neurons which are differentially distributed across the subnuclei. From spaced serial sections, the outlines of the subnuclei and the entire Sol were used to create three-dimensional computer reconstructions to display the position and extent of each component subnucleus. Our results show that the internal architecture of the human solitary nucleus is similar to that of rodents and carnivores, though there are some notable species differences.

Asunto(s)

Tronco Encefálico/anatomía & histología , Bulbo Raquídeo/anatomía & histología , Acetilcolinesterasa/metabolismo , Benzoxazinas , Tronco Encefálico/citología , Tronco Encefálico/enzimología , Colorantes , Humanos , Procesamiento de Imagen Asistido por Computador , Bulbo Raquídeo/citología , Bulbo Raquídeo/enzimología , Neuronas/citología , Oxazinas , Nervio Vago/fisiología