RESUMEN
Motor disturbances are observed in schizophrenia patients, but the neuroanatomical background is unknown. Our aim was to investigate the pyramidal cells of the primary motor cortex (BA 4) in both hemispheres of postmortem control and schizophrenia subjects-8 subjects in each group-with 2.5-5.5 h postmortem interval. The density and size of the Sternberger monoclonal incorporated antibody 32 (SMI32)-immunostained pyramidal cells in layer 3 and 5 showed no change; however, the proportion of larger pyramidal cells is decreased in layer 5. Giant pyramidal neurons (Betz cells) were investigated distinctively with SMI32- and parvalbumin (PV) immunostainings. In the right hemisphere of schizophrenia subjects, the density of Betz cells was decreased and their PV-immunopositive perisomatic input showed impairment. Part of the Betz cells contained PV in both groups, but the proportion of PV-positive cells has declined with age. The rat model of antipsychotic treatment with haloperidol and olanzapine showed no differences in size and density of SMI32-immunopositive pyramidal cells. Our results suggest that motor impairment of schizophrenia patients may have a morphological basis involving the Betz cells in the right hemisphere. These alterations can have neurodevelopmental and neurodegenerative explanations, but antipsychotic treatment does not explain them.
Asunto(s)
Lateralidad Funcional , Corteza Motora , Células Piramidales , Esquizofrenia , Anciano , Anciano de 80 o más Años , Animales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ratas , Envejecimiento , Antipsicóticos/uso terapéutico , Autopsia , Conjuntos de Datos como Asunto , Modelos Animales de Enfermedad , Lateralidad Funcional/efectos de los fármacos , Haloperidol/farmacología , Haloperidol/uso terapéutico , Inmunohistoquímica , Filamentos Intermedios/metabolismo , Corteza Motora/efectos de los fármacos , Corteza Motora/patología , Olanzapina/farmacología , Olanzapina/uso terapéutico , Parvalbúminas/metabolismo , Células Piramidales/efectos de los fármacos , Células Piramidales/patología , Ratas Sprague-Dawley , Análisis de Regresión , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/patologíaRESUMEN
BACKGROUND AND PURPOSE: Fibrocartilaginous embolism is a rare cause of ischemic myelopathy. Authors report a case of a 39-year-old woman with progressive tetraparesis and severe autonomic dysfunction. Despite of the detailed examinations, the definite diagnosis was verified by autopsy. METHODS: The patient was admitted because of progressive pain and numbness of the upper extremities and tetraparesis. Hypotonic muscles of the lower extremities with mild tetraparesis were observed. Magnetic resonance imaging showed an intramedullary lesion at the level of the cervical V-VII vertebral. Patient's tetraparesis worsened gradually to plegia with urinary retention. Expansive, rapidly progressing multiple decubiti developed, which were resistant to therapy. In spite of the complex therapy, the patient died. RESULTS: No internal disease was found to explain the death by autopsy. Multiple subacute infarctions of the cervical myelon (involving the lateral columns as well) in the territory of the anterior spinal artery were verified by neuropathological examination. The occluded vessels were filled by a material containing cartilaginous cells, while signs of atherosclerosis or thrombosis were not present. CONCLUSION: Cartilaginous embolism of spinal arteries was diagnosed.
Asunto(s)
Enfermedades de los Cartílagos , Embolia , Enfermedades de la Médula Espinal , Adulto , Enfermedades de los Cartílagos/complicaciones , Embolia/complicaciones , Femenino , Humanos , Imagen por Resonancia Magnética , Médula Espinal , Enfermedades de la Médula Espinal/complicacionesRESUMEN
Betz cells-the gigantopyramidal neurons found in high amount in the primary motor cortex-are among of the most characteristic neuronal cells. A part of them contains the calcium-binding protein parvalbumin (PV) in primates. However, less is known about these cells in the human motor cortex despite their important role in different neurological disorders. Therefore, the aim of our study was to investigate the neurochemical features and perisomatic input properties of Betz cells in control human samples with short post-mortem interval. We used different microscopic techniques to investigate the primary motor cortex of both hemispheres. The soma size and density, and expression of PV of the Betz cells were investigated. Furthermore, we used confocal fluorescent and electron microscopy to examine their perisomatic input. The soma size and density showed moderate variability among samples and hemispheres. Post-mortem interval and hemispherical localization did not influence these features. Around 70% of Betz cells expressed PV, but in less intensity than the cortical interneurons. Betz neurons receive dense perisomatic input, which are mostly VIAAT- (vesicular inhibitory amino acid transporter) and PV immunopositive. In the electron microscope, we found PV-immunolabelled terminals with asymmetric-like synaptic structure, too. Terminals with morphologically similar synaptic specialisation were also found among vGluT2- (vesicular glutamate transporter type 2) immunostained terminals contacting Betz cells. Our data suggest that Betz cells' morphological properties showed less variability among subjects and hemispheres than the density of them. Their neurochemical and perisomatic input characteristics support their role in execution of fast and precise movements.
Asunto(s)
Corteza Motora/metabolismo , Parvalbúminas/metabolismo , Células Piramidales/metabolismo , Adulto , Anciano , Femenino , Humanos , Interneuronas/metabolismo , Masculino , Persona de Mediana Edad , Terminales Presinápticos/metabolismoRESUMEN
Organization of behavior requires rapid coordination of brainstem and forebrain activity. The exact mechanisms of effective communication between these regions are presently unclear. The intralaminar thalamic nuclei (IL) probably serves as a central hub in this circuit by connecting the critical brainstem and forebrain areas. We found that GABAergic and glycinergic fibers ascending from the pontine reticular formation (PRF) of the brainstem evoked fast and reliable inhibition in the IL via large, multisynaptic terminals. This inhibition was fine-tuned through heterogeneous GABAergic and glycinergic receptor ratios expressed at individual synapses. Optogenetic activation of PRF axons in the IL of freely moving mice led to behavioral arrest and transient interruption of awake cortical activity. An afferent system with comparable morphological features was also found in the human IL. These data reveal an evolutionarily conserved ascending system that gates forebrain activity through fast and powerful synaptic inhibition of the IL.
Asunto(s)
Vías Aferentes/fisiología , Conducta Animal/fisiología , Neuronas GABAérgicas/fisiología , Glicina/metabolismo , Núcleos Talámicos Intralaminares/fisiología , Fibras Nerviosas/fisiología , Inhibición Neural/fisiología , Tegmento Pontino/fisiología , Animales , Masculino , Ratones , Optogenética , Técnicas de Placa-Clamp , Receptores de GABA/metabolismo , Receptores de Glicina/metabolismoRESUMEN
Alzheimer's disease and other age-related neurodegenerative disorders are associated with deterioration of the noradrenergic locus coeruleus (LC), a probable trigger for mood and memory dysfunction. LC noradrenergic neurons exhibit particularly high levels of somatostatin binding sites. This is noteworthy since cortical and hypothalamic somatostatin content is reduced in neurodegenerative pathologies. Yet a possible role of a somatostatin signal deficit in the maintenance of noradrenergic projections remains unknown. Here, we deployed tissue microarrays, immunohistochemistry, quantitative morphometry and mRNA profiling in a cohort of Alzheimer's and age-matched control brains in combination with genetic models of somatostatin receptor deficiency to establish causality between defunct somatostatin signalling and noradrenergic neurodegeneration. In Alzheimer's disease, we found significantly reduced somatostatin protein expression in the temporal cortex, with aberrant clustering and bulging of tyrosine hydroxylase-immunoreactive afferents. As such, somatostatin receptor 2 (SSTR2) mRNA was highly expressed in the human LC, with its levels significantly decreasing from Braak stages III/IV and onwards, i.e., a process preceding advanced Alzheimer's pathology. The loss of SSTR2 transcripts in the LC neurons appeared selective, since tyrosine hydroxylase, dopamine ß-hydroxylase, galanin or galanin receptor 3 mRNAs remained unchanged. We modeled these pathogenic changes in Sstr2(-/-) mice and, unlike in Sstr1(-/-) or Sstr4(-/-) genotypes, they showed selective, global and progressive degeneration of their central noradrenergic projections. However, neuronal perikarya in the LC were found intact until late adulthood (<8 months) in Sstr2(-/-) mice. In contrast, the noradrenergic neurons in the superior cervical ganglion lacked SSTR2 and, as expected, the sympathetic innervation of the head region did not show any signs of degeneration. Our results indicate that SSTR2-mediated signaling is integral to the maintenance of central noradrenergic projections at the system level, and that early loss of somatostatin receptor 2 function may be associated with the selective vulnerability of the noradrenergic system in Alzheimer's disease.
Asunto(s)
Enfermedad de Alzheimer/patología , Locus Coeruleus/metabolismo , Norepinefrina/metabolismo , Receptores de Somatostatina/metabolismo , Factores de Edad , Anciano , Péptidos beta-Amiloides/metabolismo , Animales , Monoaminas Biogénicas/metabolismo , Carbocianinas/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Femenino , Regulación de la Expresión Génica/genética , Humanos , Locus Coeruleus/patología , Masculino , Ratones , Ratones Transgénicos , Persona de Mediana Edad , Neuronas/metabolismo , Receptores de Somatostatina/genética , Transducción de Señal/fisiología , Somatostatina/metabolismo , Lóbulo Temporal/metabolismo , Lóbulo Temporal/patología , Tirosina 3-Monooxigenasa/metabolismo , Proteínas tau/metabolismoRESUMEN
We have examined samples from 14 donors that were prepared from 44 different anatomical regions of the brain. These samples were prepared both as frozen formalin-fixed, paraffin embedded. There were 310 frozen samples and 367 fixed samples. A total of 265 of the frozen samples were tested for RNA quality. A very high quality was obtained with 122 of these frozen samples (44%). The sample numbers were not large enough to draw conclusions about RNA quality for individual brain regions. Silver staining was performed on some samples and 5 of 7 samples tested from one donor diagnosed with Alzheimer's like dementia showed evidence of Alzheimer's disease by this method.
Asunto(s)
Enfermedad de Alzheimer/patología , Química Encefálica , ARN/análisis , Autopsia , Infarto Cerebral/complicaciones , Infarto Cerebral/patología , Demencia/etiología , Demencia/patología , Secciones por Congelación , Humanos , Esquizofrenia Paranoide/complicaciones , Esquizofrenia Paranoide/patologíaRESUMEN
Immunohistochemical techniques revealed a significant increase of poly(ADP-ribose) polymerase (PARP)-containing nuclei in the dopaminergic neurons of the substantia nigra (SN) in Parkinson disease and in diffuse Lewy body disease as compared with a group of patients with other neurodegenerative diseases and normal controls. The nuclear translocation of nuclear factor kappa B (NF-kappa B) was also noted in the same cells. The over-activation of PARP and the transcriptional activation of NF-kappa B can contribute to the pathomechanism of the disease specific lesion of the neurons in the SN. However, in another subgroup of dopaminergic cells of the SN an increased parvalbumin content was detected reflecting a natural protective mechanism against the putative increase of intracellular calcium caused by excitotoxic injury and oxidative stress.