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1.
Schizophr Res ; 256: 26-35, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37126979

RESUMO

BACKGROUND: The thalamus is central to brain functions ranging from primary sensory processing to higher-order cognition. Structural deficits in thalamic association nuclei such as the pulvinar and mediodorsal nuclei have previously been reported in schizophrenia. However, the specificity with regards to clinical presentation, and whether or not bipolar disorder (BD) is associated with similar alterations is unclear. METHODS: We investigated thalamic nuclei volumes in 334 patients with schizophrenia spectrum disorders (SSD) (median age 29 years, 59 % male), 322 patients with BD (30 years, 40 % male), and 826 healthy controls (HC) (34 years, 54 % male). Volumes of 25 thalamic nuclei were extracted from T1-weighted magnetic resonance imaging using an automated Bayesian segmentation method and compared between groups. Furthermore, we explored associations with clinical characteristics across diagnostic groups, including psychotic and mood symptoms and medication use, as well as diagnostic subtype in BD. RESULTS: Significantly smaller volumes were found in the mediodorsal, pulvinar, and lateral and medial geniculate thalamic nuclei in SSD. Similarly, smaller volumes were found in BD in the same four regions, but mediodorsal nucleus volume alterations were limited to its lateral part and pulvinar alterations to its anterior region. Smaller volumes in BD compared to HC were seen only in BD type I, not BD type II. Across diagnoses, having more negative symptoms was associated with smaller pulvinar volumes. CONCLUSIONS: Structural alterations were found in both SSD and BD, mainly in the thalamic association nuclei. Structural deficits in the pulvinar may be of relevance for negative symptoms.


Assuntos
Esquizofrenia , Humanos , Masculino , Adulto , Feminino , Esquizofrenia/diagnóstico , Teorema de Bayes , Núcleos Talâmicos/diagnóstico por imagem , Núcleos Talâmicos/patologia , Tálamo/patologia , Núcleo Mediodorsal do Tálamo , Imageamento por Ressonância Magnética/métodos
2.
Cell Stem Cell ; 30(5): 677-688.e5, 2023 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-37019105

RESUMO

Human brain organoids provide unique platforms for modeling several aspects of human brain development and pathology. However, current brain organoid systems mostly lack the resolution to recapitulate the development of finer brain structures with subregional identity, including functionally distinct nuclei in the thalamus. Here, we report a method for converting human embryonic stem cells (hESCs) into ventral thalamic organoids (vThOs) with transcriptionally diverse nuclei identities. Notably, single-cell RNA sequencing revealed previously unachieved thalamic patterning with a thalamic reticular nucleus (TRN) signature, a GABAergic nucleus located in the ventral thalamus. Using vThOs, we explored the functions of TRN-specific, disease-associated genes patched domain containing 1 (PTCHD1) and receptor tyrosine-protein kinase (ERBB4) during human thalamic development. Perturbations in PTCHD1 or ERBB4 impaired neuronal functions in vThOs, albeit not affecting the overall thalamic lineage development. Together, vThOs present an experimental model for understanding nuclei-specific development and pathology in the thalamus of the human brain.


Assuntos
Núcleos Talâmicos , Tálamo , Humanos , Núcleos Talâmicos/patologia , Núcleos Talâmicos/fisiologia , Neurônios/fisiologia , Organoides
3.
Brain Behav ; 13(4): e2968, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36924055

RESUMO

INTRODUCTION: This study aimed to investigate the alterations in individual thalamic nuclei volumes in patients with occipital lobe epilepsy (OLE) compared with those of healthy controls, and to analyze the intrinsic thalamic network based on these volumes using graph theory. METHODS: Thirty adult patients with newly diagnosed OLE and 42 healthy controls were retrospectively enrolled (mean age, 33.8 ± 17.0 and 32.2 ± 6.6 years, respectively). The study participants underwent brain magnetic resonance imaging with three-dimensional T1-weighted imaging. The right and left total thalamic and individual thalamic nuclei volumes were obtained using the FreeSurfer program. Then, the intrinsic thalamic network was calculated based on the individual thalamic nuclei volumes and graph theory using a BRAPH program. RESULTS: There were no differences in the right and left whole-thalamic volumes between the two groups (0.445% vs. 0.469%, p = .142 and 0.481% vs. 0.490%, p = .575, respectively). However, significant differences were observed in the volumes of several thalamic nuclei between the two groups. The right medial geniculate and right suprageniculate nuclei volumes were increased (0.0077% vs. 0.0064%, p = .0003 and 0.0013% vs. 0.0010%, p = .0004, respectively), whereas the right and left parafascicular nuclei volumes were decreased in patients with OLE compared with those in healthy controls (0.0038% vs. 0.0048%, p < .0001 and 0.0037% vs. 0.0045%, p = .0001, respectively). There were no differences in the network measures regarding intrinsic thalamic network between the two groups. CONCLUSION: We successfully demonstrated the alterations in individual thalamic nuclei volumes, especially the increased medial geniculate and suprageniculate, and decreased parafascicular nuclei volumes in patients with OLE compared with those of healthy controls despite no changes in the whole-thalamic volumes. These findings suggest an important role of the thalamus in the epileptic network of OLE.


Assuntos
Epilepsias Parciais , Tálamo , Adulto , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Estudos Retrospectivos , Tálamo/diagnóstico por imagem , Tálamo/patologia , Núcleos Talâmicos/diagnóstico por imagem , Núcleos Talâmicos/patologia , Epilepsias Parciais/patologia , Encéfalo , Imageamento por Ressonância Magnética/métodos
4.
Brain Behav ; 12(7): e2639, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35676235

RESUMO

INTRODUCTION: Trauma reexperiencing is dominated by recollection of sensory-perceptual elements of the trauma, pointing to involvement of the sensory thalamus. This study examined posttraumatic stress symptoms in relation to volumes of thalamic nuclei that were grouped based on their predominant functions. We hypothesized that reexperiencing, controlling for other symptom dimensions, would correlate with volumes of thalamic nuclei involved in primary and higher-order sensory processing. METHODS: Seventy-two trauma-exposed adults were interviewed with the Clinician Administered PTSD Scale for DSM-IV and underwent 3T magnetic resonance imaging. Scores were derived for reexperiencing, anxious arousal, dysphoric arousal, emotional numbing, and avoidance symptoms. These were entered as simultaneous predictors in five separate regression analyses, with age, sex, and total thalamus volume as covariates, predicting volumesf of five thalamus nuclear groupings corrected for intracranial volume: Specific sensory, associative-sensory, associative-cognitive, intralaminar, and motor groupings. RESULTS: Reexperiencing symptoms were significantly positively correlated with volumes of the motor thalamic grouping, which included the ventral anterior, ventral lateral, and ventromedial nuclei. Anxious arousal was significantly negatively correlated with volumes of all five thalamic groupings. CONCLUSIONS: Reexperiencing symptoms were correlated with volumes of the motor thalamus, while anxious arousal symptoms were related to all thalamic subregion volumes. Thalamic nuclei involved in motor functions, including oculomotor control and motor planning, may be implicated in posttraumatic reexperiencing symptoms.


Assuntos
Transtornos de Estresse Pós-Traumáticos , Adulto , Ansiedade/diagnóstico por imagem , Nível de Alerta , Humanos , Transtornos de Estresse Pós-Traumáticos/diagnóstico por imagem , Núcleos Talâmicos/patologia , Tálamo/diagnóstico por imagem , Tálamo/patologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-32620531

RESUMO

BACKGROUND: Several studies in patients with schizophrenia have demonstrated an abnormal thalamic volume and thalamocortical connectivity. Specifically, hyperconnectivity with somatosensory areas has been related to the presence of auditory hallucinations (AHs). The 22q11.2 deletion syndrome is a neurogenetic disorder conferring proneness to develop schizophrenia, and deletion carriers (22qdel carriers) experience hallucinations to a greater extent than the general population. METHODS: We acquired 442 consecutive magnetic resonance imaging scans from 120 22qdel carriers and 110 control subjects every 3 years (age range: 8-35 years). The volume of thalamic nuclei was obtained with FreeSurfer and was compared between 22qdel carriers and control subjects and between 22qdel carriers with and without AHs. In a subgroup of 76 22qdel carriers, we evaluated the functional connectivity between thalamic nuclei affected in patients experiencing AHs and cortical regions. RESULTS: As compared with control subjects, 22qdel carriers had lower and higher volumes of nuclei involved in sensory processing and cognitive functions, respectively. 22qdel carriers with AHs had a smaller volume of the medial geniculate nucleus, with deviant trajectories showing a steeper volume decrease from childhood with respect to those without AHs. Moreover, we showed an aberrant development of nuclei intercalated between the prefrontal cortex and hippocampus (the anteroventral and medioventral reuniens nuclei) and hyperconnectivity of the medial geniculate nucleus and anteroventral nucleus with the auditory cortex and Wernicke's area. CONCLUSIONS: The increased connectivity of the medial geniculate nucleus and anteroventral nucleus to the auditory cortex might be interpreted as a lack of maturation of thalamocortical connectivity. Overall, our findings point toward an aberrant development of thalamic nuclei and an immature pattern of connectivity with temporal regions in relation to AHs.


Assuntos
Síndrome de DiGeorge , Alucinações , Núcleos Talâmicos , Adolescente , Adulto , Criança , Corpos Geniculados , Humanos , Núcleos Talâmicos/patologia , Núcleos Talâmicos/fisiopatologia , Tálamo/diagnóstico por imagem , Adulto Jovem
6.
Brain Nerve ; 67(12): 1471-80, 2015 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-26618761

RESUMO

Attention is the process by which information and selection occurs, the thalamus plays an important role in the selective attention of visual and auditory information. Selective attention is a conscious effort; however, it occurs subconsciously, as well. The lateral geniculate body (LGB) filters visual information before it reaches the cortex (bottom-up attention). The thalamic reticular nucleus (TRN) provides a strong inhibitory input to both the LGB and pulvinar. This regulation involves focusing a spotlight on important information, as well as inhibiting unnecessary background information. Behavioral contexts more strongly modulate activity of the TRN and pulvinar influencing feedforward and feedback information transmission between the frontal, temporal, parietal and occipital cortical areas (top-down attention). The medial geniculate body (MGB) filters auditory information the TRN inhibits the MGB. Attentional modulation occurring in the auditory pathway among the cochlea, cochlear nucleus, superior olivary complex, and inferior colliculus is more important than that of the MGB and TRN. We also discuss the attentional consequence of thalamic hemorrhage.


Assuntos
Atenção/fisiologia , Vias Auditivas/fisiologia , Núcleos Talâmicos/patologia , Tálamo/patologia , Tálamo/fisiopatologia , Vias Auditivas/fisiopatologia , Corpos Geniculados/patologia , Humanos , Neurônios/fisiologia , Tálamo/fisiologia
7.
Neuroradiol J ; 28(6): 584-6, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26463006

RESUMO

Bilateral thalamic glioma is one of the rarest tumor occurrences, representing a small fraction of thalamic gliomas, which only accounts for 1-1.5% of all brain tumors. It is usually a diffuse, low-grade astrocytoma (WHO grade II), seen mainly in adults, with approximately 25% of them involving children under the age of 15. Radiotherapy is the main mode of treatment since surgical intervention is limited to a role of biopsy and management of secondary effects, due to the deep brain location of the lesion and the complexity of the involved structures. We report a 1-year follow-up of a 55-year-old female patient with bilateral WHO grade II thalamic astrocytoma. Following histological and neuroradiological consensus regarding the diagnosis, the patient was referred for radiotherapy. The effectiveness of available therapy and long-term neuroradiological follow-up is not reliably established due to rapid fatal evolution following diagnosis. Contrary to the norm, our patient showed stable disease with radiotherapy for a 1-year period.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Doenças Talâmicas/patologia , Astrocitoma/diagnóstico por imagem , Astrocitoma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Feminino , Glioma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Cintilografia , Doenças Talâmicas/diagnóstico por imagem , Núcleos Talâmicos/diagnóstico por imagem , Núcleos Talâmicos/patologia , Tálamo/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento
8.
Curr Neurol Neurosci Rep ; 13(4): 341, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23423537

RESUMO

Agrypnia (from the Greek: to chase sleep) excitata (AE) is a syndrome characterized by loss of sleep and permanent motor and autonomic hyperactivation (excitata). Disruption of the sleep-wake rhythm consists in the disappearance of spindle-delta activities, and the persistence of stage 1 non-rapid eye movement (NREM) sleep. Rapid eye movement (REM) sleep persists but fails to stabilize, appearing in short recurrent episodes, isolated, or mixed with stage 1 NREM sleep. Diurnal and nocturnal motor, autonomic and hormonal overactivity is the second hallmark of AE. Of particular interest is the finding that norepinephrine secretion is extremely elevated at all hours of the day and night whereas the nocturnal melatonin peak is lacking. Oneiric stupor is probably an exclusive sign of AE and consists in the recurrence of stereotyped gestures mimicking simple daily life activities. Agrypnia excitata aptly defines 3 different clinical conditions, fatal familial insomnia (FFI), an autosomal dominant prion disease, Morvan syndrome (MS), an autoimmune encephalitis, and delirium tremens (DT), the alcohol withdrawal syndrome. Agrypnia excitata is due to an intralimbic disconnection releasing the hypothalamus and brainstem reticular formation from cortico-limbic inhibitory control. This pathogenetic mechanism is visceral thalamus degeneration in FI, whereas it may depend on autoantibodies blocking voltage-gated potassium (VGK) channels within the limbic system in MS, and in the sudden changes in gabaergic synapses down-regulated by chronic alcohol abuse within the limbic system in DT.


Assuntos
Delirium por Abstinência Alcoólica/complicações , Insônia Familiar Fatal/complicações , Mioquimia/complicações , Agitação Psicomotora/etiologia , Distúrbios do Início e da Manutenção do Sono/etiologia , Delirium por Abstinência Alcoólica/fisiopatologia , Animais , Atrofia , Autoanticorpos/imunologia , Autoantígenos/imunologia , Modelos Animais de Doenças , Humanos , Hipotálamo/fisiopatologia , Insônia Familiar Fatal/diagnóstico , Insônia Familiar Fatal/fisiopatologia , Sistema Límbico/fisiopatologia , Melatonina/deficiência , Camundongos , Mioquimia/imunologia , Mioquimia/fisiopatologia , Norepinefrina/metabolismo , Polissonografia , Canais de Potássio de Abertura Dependente da Tensão da Membrana/imunologia , Agitação Psicomotora/fisiopatologia , Formação Reticular/fisiopatologia , Distúrbios do Início e da Manutenção do Sono/fisiopatologia , Fases do Sono/fisiologia , Transtorno de Movimento Estereotipado/etiologia , Taquicardia/etiologia , Núcleos Talâmicos/patologia , Núcleos Talâmicos/fisiopatologia
9.
Neurocase ; 17(4): 345-52, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21207314

RESUMO

INTRODUCTION: The thalamus is one of the strategic diencephalic structures of the human brain. The artery of Percheron, an asymmetrical common trunk arising from a P1 segment of the posterior cerebral artery, is a peculiar presentation of the three variants involved in the irrigation of the paramedian thalamic territory. Occlusion of this artery results in bilateral median thalamic infarction. The paramedian syndrome includes an acute loss or reduction of consciousness, often associated with oculomotor and neuropsychological disturbances. PATIENTS AND METHODS: We present three cases of bilateral paramedian thalamic infarction with onset of acute coma, followed by fluctuations in the level of consciousness, memory, and behavioural alterations. A neuroradiological study with MRI identified individual thalamic nuclei, and a complete neuropsychological study was performed one month after onset of ictus. RESULTS: One of the patients showed severe memory and executive function impairments without improvement of vertical gaze palsy. The other two patients presented with mild executive dysfunction with complete resolution of neurological symptoms. Neuroimaging results showed a bilateral lesion of the dorsomedial nuclei in the three patients. CONCLUSIONS: Severe amnesia has been associated with an affection of the structures of the paramedian thalamic territory. Presently, the role of the dorsomedial nucleus remains controversial, with the suggestion that memory deficits observed in this type of lesion could be secondary to executive function deficits. In our case, the patient with the most severe dysexecutive deficit presented the most severe memory impairments.


Assuntos
Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologia , Tálamo/irrigação sanguínea , Tálamo/patologia , Idoso , Infarto Cerebral/complicações , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Núcleos Talâmicos/patologia , Núcleos Talâmicos/fisiopatologia
10.
J Neurosci ; 31(4): 1302-12, 2011 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-21273415

RESUMO

The modification of the neural cell adhesion molecule (NCAM) with polysialic acid (polySia) is tightly linked to neural development. Genetic ablation of the polySia-synthesizing enzymes ST8SiaII and ST8SiaIV generates polySia-negative but NCAM-positive (II(-/-)IV(-/-)) mice characterized by severe defects of major brain axon tracts, including internal capsule hypoplasia. Here, we demonstrate that misguidance of thalamocortical fibers and deficiencies of corticothalamic connections contribute to internal capsule defects in II(-/-)IV(-/-) mice. Thalamocortical fibers cross the primordium of the reticular thalamic nucleus (Rt) at embryonic day 14.5, before they fail to turn into the ventral telencephalon, thus deviating from their normal trajectory without passing through the internal capsule. At postnatal day 1, a reduction and massive disorganization of fibers traversing the Rt was observed, whereas terminal deoxynucleotidyl transferase dUTP nick end labeling and cleaved caspase-3 staining indicated abundant apoptotic cell death of Rt neurons at postnatal day 5. Furthermore, during postnatal development, the number of Rt neurons was drastically reduced in 4-week-old II(-/-)IV(-/-) mice, but not in the NCAM-deficient N(-/-) or II(-/-)IV(-/-)N(-/-) triple knock-out animals displaying no internal capsule defects. Thus, degeneration of the Rt in II(-/-)IV(-/-) mice may be a consequence of malformation of thalamocortical and corticothalamic fibers providing major excitatory input into the Rt. Indeed, apoptotic death of Rt neurons could be induced by lesioning corticothalamic fibers on whole-brain slice cultures. We therefore propose that anterograde transneuronal degeneration of the Rt in polysialylation-deficient, NCAM-positive mice is caused by defective afferent innervation attributable to thalamocortical pathfinding defects.


Assuntos
Córtex Cerebral/patologia , Neurônios/patologia , Ácidos Siálicos/genética , Tálamo/patologia , Vias Aferentes/anormalidades , Animais , Animais Recém-Nascidos , Apoptose , Axônios/patologia , Córtex Cerebral/embriologia , Córtex Cerebral/crescimento & desenvolvimento , Dopamina/metabolismo , Cápsula Interna/anormalidades , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fibras Nervosas/patologia , Moléculas de Adesão de Célula Nervosa/genética , Núcleos Talâmicos/embriologia , Núcleos Talâmicos/crescimento & desenvolvimento , Núcleos Talâmicos/patologia , Tálamo/embriologia , Tálamo/crescimento & desenvolvimento
11.
Arch Gen Psychiatry ; 67(9): 955-64, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20819989

RESUMO

CONTEXT: The basal ganglia and thalamus together connect in parallel closed-loop circuits with the cortex. Previous imaging studies have shown modifications of the basal ganglia and cortical targets in individuals with Tourette syndrome (TS), but less is known regarding the role of the thalamus in TS pathogenesis. OBJECTIVE: To study the morphological features of the thalamus in children and adults with TS. DESIGN: A cross-sectional, case-control study using anatomical magnetic resonance imaging. SETTING: University research center. PARTICIPANTS: The 283 participants included 149 with TS and 134 normal control individuals aged 6 to 63 years. MAIN OUTCOME MEASURES: Conventional volumes and measures of surface morphology of the thalamus. RESULTS: Analyses of conventional volumes and surface morphology were consistent in demonstrating an enlargement in TS-affected thalami. Overall volumes were 5% larger in the group composed of children and adults with TS. Statistical maps of surface contour demonstrated enlargement over the lateral thalamus. Post hoc testing indicated that differences in IQ, comorbid illnesses, and medication use did not account for these findings. CONCLUSIONS: Morphological abnormalities in the thalamus, together with the disturbances reported in the sensorimotor cortex, striatum, and globus pallidus, support the hypothesis of a circuitwide disorder within motor pathways in TS. The connectivity and function of the numerous and diverse thalamic nuclei within cortical-subcortical circuits constitute an anatomical crossroad wherein enlargement of motor nuclei may represent activity-dependent hypertrophy within this component of cortical-subcortical motor circuits, or an adaptive response within a larger putative compensatory system that could thereby directly modulate activity in motor circuits to attenuate the severity of tics.


Assuntos
Núcleos Talâmicos/patologia , Síndrome de Tourette/patologia , Adulto , Estudos de Casos e Controles , Córtex Cerebral/patologia , Criança , Feminino , Humanos , Hipertrofia/patologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Córtex Motor/patologia , Vias Neurais/patologia , Tálamo/patologia
12.
Prog Neurobiol ; 89(4): 383-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19819292

RESUMO

Recently, a series of studies have given rise to and provided evidence for the hypothesis that the nucleus submedius (Sm) in the medial thalamus is involved in modulation of nociception. The Sm, ventrolateral orbital cortex (VLO) and the periaqueductal gray (PAG) constitute a pain modulatory pathway, activation of which leads to activation of the PAG-brainstem descending inhibitory system and depression of the nociceptive inputs in the spinal cord and trigeminal nucleus. Other studies have indicated that the Sm-VLO-PAG pathway plays an important role in the analgesia induced by electroacupuncture stimulation of the acupuncture point (acupoint) for exciting small diameter fiber (A-delta and C group) afferents. Opioid peptides, serotonin, dopamine, glutamate and their related receptors are involved in Sm- and/or VLO-mediated descending antinociception, and a GABAergic disinhibitory mechanism participates in mediating the antinociception induced by activation of mu-opioid receptors, serotonin 1(A) receptors, and dopamine D(2)-like receptors. This review describes these findings, which provide important new insights into the roles of the thalamus and cerebral cortex in descending pain modulation.


Assuntos
Lobo Frontal/fisiopatologia , Nociceptores/fisiologia , Dor/patologia , Núcleos Talâmicos/fisiopatologia , Analgesia por Acupuntura/métodos , Animais , Humanos , Vias Neurais/fisiopatologia , Neurônios/fisiologia , Neurotransmissores/metabolismo , Manejo da Dor , Substância Cinzenta Periaquedutal/fisiopatologia , Receptores de Neurotransmissores/fisiologia , Núcleos Talâmicos/patologia
13.
J Neurochem ; 111(2): 452-9, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19686244

RESUMO

Wernicke's encephalopathy is a cerebral disorder caused by thiamine (vitamin B(1)) deficiency (TD). Neuropathologic consequences of TD include region-selective neuronal cell loss and blood-brain barrier (BBB) breakdown. Early increased expression of the endothelial isoform of nitric oxide synthase (eNOS) occurs selectively in vulnerable brain regions in TD. We hypothesize that region-selective eNOS induction in TD leads to altered expression of tight junction proteins and BBB breakdown. In order to address this issue, TD was induced in C57BL/6 wild-type (WT) and eNOS(-/-) mice by feeding a thiamine-deficient diet and treatment with the thiamine antagonist pyrithiamine. Pair-fed control mice were fed the same diet with additional thiamine. In medial thalamus of TD-WT mice (vulnerable area), increased heme oxygenase-1 and S-nitrosocysteine immunostaining was observed in vessel walls, compared to pair-fed control-WT mice. Concomitant increases in IgG extravasation, decreases in expression of the tight junction proteins occludin, zona occludens-1 and zona occludens-2, and up-regulation of matrix metalloproteinase-9 in endothelial cells were observed in the medial thalamus of TD-WT mice. eNOS gene deletion restored these BBB alterations, suggesting that eNOS-derived nitric oxide is a major factor leading to cerebrovascular alterations in TD. However, eNOS gene deletion only partially attenuated TD-related neuronal cell loss, suggesting the presence of mechanisms additional to BBB disruption in the pathogenesis of these changes.


Assuntos
Barreira Hematoencefálica/fisiologia , Degeneração Neural/fisiopatologia , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Núcleos Talâmicos/fisiologia , Deficiência de Tiamina/fisiopatologia , Animais , Antimetabólitos/toxicidade , Modelos Animais de Doenças , Lobo Frontal/patologia , Lobo Frontal/fisiologia , Imunoglobulina G/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Degeneração Neural/induzido quimicamente , Degeneração Neural/metabolismo , Estresse Oxidativo/fisiologia , Piritiamina/toxicidade , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Núcleos Talâmicos/patologia , Deficiência de Tiamina/metabolismo
14.
Neurobiol Dis ; 25(1): 150-62, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17046272

RESUMO

Infantile neuronal ceroid lipofuscinosis (INCL) is caused by deficiency of the lysosomal enzyme, palmitoyl protein thioesterase 1 (PPT1). We have investigated the onset and progression of pathological changes in Ppt1 deficient mice (Ppt1-/-) and the development of their seizure phenotype. Surprisingly, cortical atrophy and neuron loss occurred only late in disease progression but were preceded by localized astrocytosis within individual thalamic nuclei and the progressive loss of thalamic neurons that relay different sensory modalities to the cortex. This thalamic neuron loss occurred first within the visual system and only subsequently in auditory and somatosensory relay nuclei or the inhibitory reticular thalamic nucleus. The loss of granule neurons and GABAergic interneurons followed in each corresponding cortical region, before the onset of seizure activity. These findings provide novel evidence for successive neuron loss within the thalamus and cortex in Ppt1-/- mice, revealing the thalamus as an important early focus of INCL pathogenesis.


Assuntos
Córtex Cerebral/patologia , Lipofuscinoses Ceroides Neuronais/patologia , Neurônios/patologia , Tálamo/patologia , Tioléster Hidrolases/fisiologia , Envelhecimento/patologia , Animais , Astrócitos/patologia , Atrofia/patologia , Modelos Animais de Doenças , Progressão da Doença , Eletroencefalografia , Gliose/patologia , Interneurônios/patologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia de Fluorescência , Neuroglia/patologia , Fenótipo , Convulsões/etiologia , Sinapses/patologia , Núcleos Talâmicos/patologia , Tioléster Hidrolases/genética
15.
Int J Neuropsychopharmacol ; 10(2): 231-44, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16448581

RESUMO

Dementia with Lewy bodies (DLB) is characterized by progressive dementia with two of three core symptoms; Parkinsonism, visual hallucinations or disturbances of consciousness/fluctuating attention. Dementia in Parkinson's disease (PDD) has similar neuropsychiatric characteristics. Reduced nigrothalamic dopamine and altered thalamic D2 receptors may mediate some of the non-motor symptoms of DLB and PDD. The study aims were to ascertain whether thalamic D2 density was altered in Parkinson's disease (PD), PDD and DLB, and whether D2 density was related to core symptoms. Thalamic D2 receptor binding was measured by post-mortem autoradiography in 18 cases of DLB, 13 PDD, 6 PD and 14 normal elderly controls. Highest D2 density in control cases was in the intralaminar, midline, anterior and mediodorsal nuclei. In PD without dementia D2 binding was elevated above controls in all thalamic regions, significantly in reticular, laterodorsal, centromedian, ventral centromedian, parafascicular, paraventricular, ventroposterior, ventrolateral posterior, and ventrointermedius nuclei. Compared to controls, DLB cases with Parkinsonism (DLB+EPS) had significantly elevated D2 receptor density in laterodorsal and ventrointermedius nuclei; PDD cases had significantly raised density in the ventrointermedius, and DLB cases without Parkinsonism (DLB-EPS) did not show increased D2 density in any areas. In DLB and PDD cases with disturbances of consciousness, cases treated with neuroleptics had higher D2 binding in all thalamic regions, significantly in the mediodorsal and ventrolateral posterior nuclei. D2 receptor binding did not vary with cognitive decline (MMSE) or visual hallucinations, but was significantly higher with increased extrapyramidal symptoms.


Assuntos
Demência/metabolismo , Doença por Corpos de Lewy/metabolismo , Doença de Parkinson/metabolismo , Receptores de Dopamina D2/metabolismo , Tálamo/metabolismo , Idoso , Idoso de 80 Anos ou mais , Antipsicóticos/uso terapêutico , Autopsia , Autorradiografia , Doenças dos Gânglios da Base/metabolismo , Doenças dos Gânglios da Base/psicologia , Córtex Cerebral/patologia , Transtornos da Consciência/metabolismo , Transtornos da Consciência/psicologia , Demência/etiologia , Demência/psicologia , Feminino , Alucinações/metabolismo , Alucinações/psicologia , Humanos , Corpos de Lewy/patologia , Doença por Corpos de Lewy/patologia , Doença por Corpos de Lewy/psicologia , Masculino , Transtornos dos Movimentos/metabolismo , Transtornos dos Movimentos/psicologia , Testes Neuropsicológicos , Doença de Parkinson/complicações , Doença de Parkinson/psicologia , Núcleos Talâmicos/metabolismo , Núcleos Talâmicos/patologia , Tálamo/patologia
16.
Am J Psychiatry ; 163(3): 463-9, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16513868

RESUMO

OBJECTIVE: Functional and structural magnetic resonance imaging (MRI) was used to investigate relationships among structure, functional activation, and cognitive deficits related to the thalamus in individuals with schizophrenia and healthy comparison subjects. METHOD: Thirty-six schizophrenia subjects and 28 healthy comparison subjects matched by age, gender, race, and parental socioeconomic status underwent structural and functional MRI while performing a series of memory tasks, including an N-back task (working memory), intentional memorization of a series of pictures or words (episodic encoding), and a yes/no recognition task. Functional activation magnitudes in seven regions of interest within the thalamic complex, as defined by anatomical and functional criteria, were computed for each group. RESULTS: Participants with schizophrenia exhibited decreased activation within the whole thalamus, the anterior nuclei, and the medial dorsal nucleus. These nuclei overlap with subregions of the thalamic surface that the authors previously reported to exhibit morphological abnormalities in schizophrenia. However, there were no significant correlations between specific dimensions of thalamic shape variation (i.e., eigenvectors) and the activation patterns within thalamic regions of interest. Better performance on the working memory task among individuals with schizophrenia was significantly associated with increased activation in the anterior nuclei, the centromedian nucleus, the pulvinar, and the ventrolateral nuclei. CONCLUSIONS: These results suggest that there are limited relationships between morphological and functional abnormalities of the thalamus in schizophrenia subjects and highlight the importance of investigating relationships between brain structure and function.


Assuntos
Transtornos Cognitivos/patologia , Transtornos Cognitivos/fisiopatologia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Desempenho Psicomotor/fisiologia , Esquizofrenia/patologia , Esquizofrenia/fisiopatologia , Tálamo/patologia , Tálamo/fisiopatologia , Adulto , Encéfalo/patologia , Encéfalo/fisiopatologia , Mapeamento Encefálico , Transtornos Cognitivos/diagnóstico , Feminino , Humanos , Masculino , Núcleo Mediodorsal do Tálamo/patologia , Núcleo Mediodorsal do Tálamo/fisiopatologia , Testes Neuropsicológicos/estatística & dados numéricos , Escalas de Graduação Psiquiátrica , Esquizofrenia/diagnóstico , Análise e Desempenho de Tarefas , Núcleos Talâmicos/patologia , Núcleos Talâmicos/fisiopatologia
17.
Stroke ; 34(9): 2264-78, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12933968

RESUMO

BACKGROUND: This article reviews the anatomy, connections, and functions of the thalamic nuclei, their vascular supply, and the clinical syndromes that result from thalamic infarction. SUMMARY OF REVIEW: Thalamic nuclei are composed of 5 major functional classes: reticular and intralaminar nuclei that subserve arousal and nociception; sensory nuclei in all major domains; effector nuclei concerned with motor function and aspects of language; associative nuclei that participate in high-level cognitive functions; and limbic nuclei concerned with mood and motivation. Vascular lesions destroy these nuclei in different combinations and produce sensorimotor and behavioral syndromes depending on which nuclei are involved. Tuberothalamic territory strokes produce impairments of arousal and orientation, learning and memory, personality, and executive function; superimposition of temporally unrelated information; and emotional facial paresis. Paramedian infarcts cause decreased arousal, particularly if the lesion is bilateral, and impaired learning and memory. Autobiographical memory impairment and executive failure result from lesions in either of these vascular territories. Language deficits result from left paramedian lesions and from left tuberothalamic lesions that include the ventrolateral nucleus. Right thalamic lesions in both these vascular territories produce visual-spatial deficits, including hemispatial neglect. Inferolateral territory strokes produce contralateral hemisensory loss, hemiparesis and hemiataxia, and pain syndromes that are more common after right thalamic lesions. Posterior choroidal lesions result in visual field deficits, variable sensory loss, weakness, dystonia, tremors, and occasionally amnesia and language impairment. CONCLUSIONS: These vascular syndromes reflect the reciprocal cerebral cortical-thalamic connections that have been interrupted and provide insights into the functional properties of the thalamus.


Assuntos
Transtornos Cerebrovasculares/diagnóstico , Transtornos Cerebrovasculares/fisiopatologia , Tálamo/irrigação sanguínea , Tálamo/fisiopatologia , Animais , Infarto Cerebral/diagnóstico , Infarto Cerebral/patologia , Infarto Cerebral/fisiopatologia , Transtornos Cerebrovasculares/patologia , Humanos , Imageamento por Ressonância Magnética , Núcleos Talâmicos/irrigação sanguínea , Núcleos Talâmicos/patologia , Núcleos Talâmicos/fisiopatologia , Tálamo/patologia
18.
Dev Med Child Neurol ; 45(3): 207-12, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12613779

RESUMO

We describe the coexistence of Asperger and Tourette syndromes (AS and TS) caused by discrete hypoxic-ischaemic necrosis of the midbrain, infrathalamic and thalamic nuclei, and striatum in an adolescent male with positive family history for tics and obsessive-compulsive disorder. Behavioural ratings, cognitive tests, and volumetric measurements of the basal ganglia were performed in the patient and five other individuals with AS-TS unassociated with MRI lesions. Cognitive deficits in attentional, executive, and visual-spatial domains were found both in the patient and control AS-TS group, though deficits were more severe in the former. MRI showed reduction of the left basal ganglia volume compared with the right in the patient, whereas the control group showed reduction of right basal ganglia volume compared with the left. It is suggested that individuals with a genetic predisposition to TS may develop AS and TS after involvement of midbrain and related components of basal ganglia-thalamocortical circuits normally implicated in the integration of emotional, cognitive, and motor functions.


Assuntos
Síndrome de Asperger/complicações , Síndrome de Asperger/patologia , Corpo Estriado/patologia , Mesencéfalo/patologia , Núcleos Talâmicos/patologia , Tálamo/patologia , Síndrome de Tourette/complicações , Síndrome de Tourette/patologia , Adolescente , Adulto , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Índice de Gravidade de Doença , Teste de Sequência Alfanumérica
19.
Stroke ; 33(12): 3006-11, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12468804

RESUMO

BACKGROUND AND PURPOSE: After focal cerebral ischemia, depending on its localization and extent, secondary neuronal damage may occur that is remote from the initial lesion. In this study differences in secondary damage of the ventroposterior thalamic nucleus (VPN) and the reticular thalamic nucleus (RTN) were investigated with the use of different ischemia models. METHODS: Transient middle cerebral artery occlusion (MCAO) leads to cortical infarction, including parts of the basal ganglia such as the globus pallidus, and to widespread edema. Photothrombotic ischemia generates pure cortical infarcts sparing the basal ganglia and with only minor edema. Neuronal degeneration was quantified within the ipsilateral RTN and VPN 14 days after ischemia. Glial reactions were studied with the use of immunohistochemistry. RESULTS: MCAO resulted in delayed neuronal cell loss of the ipsilateral VPN and RTN. Glial activation occurred in both nuclei beginning after 24 hours. Photothrombotic ischemia resulted in delayed neuronal cell loss only within the VPN. Even 2 weeks after photothrombotic ischemia, glial activation could only be seen within the VPN. CONCLUSIONS: Pure cortical infarcts after photothrombotic ischemia, without major edema and without effects on the globus pallidus of the basal ganglia, only lead to secondary VPN damage that is possibly due to retrograde degeneration. MCAO, which results in infarction of cortex and globus pallidus and which causes widespread edema, leads to secondary damage in the VPN and RTN. Thus, additional RTN damage may be due to loss of protective GABAergic input from the globus pallidus to the RTN or due to the extensive edema. Retrograde degeneration is not possible because the RTN, in contrast to the VPN, has no efferents to the cortex.


Assuntos
Isquemia Encefálica/patologia , Infarto da Artéria Cerebral Média/patologia , Neurônios/patologia , Núcleos Talâmicos/irrigação sanguínea , Núcleos Talâmicos/patologia , Animais , Gânglios da Base/irrigação sanguínea , Gânglios da Base/patologia , Isquemia Encefálica/etiologia , Contagem de Células , Morte Celular , Córtex Cerebral/irrigação sanguínea , Córtex Cerebral/patologia , Modelos Animais de Doenças , Progressão da Doença , Imuno-Histoquímica , Infarto da Artéria Cerebral Média/complicações , Fotocoagulação , Masculino , Neuroglia/patologia , Ratos , Ratos Sprague-Dawley , Tálamo/irrigação sanguínea , Tálamo/patologia , Fatores de Tempo
20.
J Neurosci ; 22(21): 9352-7, 2002 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-12417660

RESUMO

Axon guidance cues of the ephrin ligand family have been hypothesized to regulate the formation of thalamocortical connections, but in vivo evidence for such a role has not been examined directly. To test whether ephrin-mediated repulsive cues participate in sorting the projections originating from distinct thalamic nuclei, we analyzed the organization of somatosensory and anterior cingulate afferents postnatally in mice lacking ephrin-A5 gene expression. Projections from ventrobasal and laterodorsal nuclei to their respective sensory and limbic cortical areas developed normally. However, a portion of limbic thalamic neurons from the laterodorsal nucleus also formed additional projections to somatosensory cortical territories, thus maintaining inappropriate dual projections to multiple cortical regions. These results suggest that ephrin-A5 is not required for the formation of normal cortical projections from the appropriate thalamic nuclei, but rather acts as a guidance cue that restricts limbic thalamic axons from inappropriate neocortical regions.


Assuntos
Córtex Cerebral/patologia , Efrina-A5/deficiência , Sistema Límbico/patologia , Malformações do Sistema Nervoso/patologia , Tálamo/patologia , Animais , Contagem de Células , Córtex Cerebral/anormalidades , Efrina-A5/genética , Corantes Fluorescentes , Giro do Cíngulo/patologia , Homozigoto , Sistema Límbico/anormalidades , Camundongos , Camundongos Knockout , Malformações do Sistema Nervoso/genética , Neurônios/patologia , Núcleos Talâmicos/patologia , Tálamo/anormalidades
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