Quantitative evidence for neurofilament heavy subunit aggregation in motor neurons of spinal cords of patients with amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS), a neurodegenerative disease of unknown etiology, affects motor neurons leading to atrophy of skeletal muscles, paralysis and death. There is evidence for the accumulation of neurofilaments (NF) in motor neurons of the spinal cord in ALS cases. NF are major structural elements of the neuronal cytoskeleton. They play an important role in cell architecture and differentiation and in the determination and maintenance of fiber caliber. They are composed of three different polypeptides: light (NF-L), medium (NF-M) and heavy (NF-H) subunits. In the present study, we performed a morphological and quantitative immunohistochemical analysis to evaluate the accumulation of NF and the presence of each subunit in control and ALS cases. Spinal cords from patients without neurological disease and from ALS patients were obtained at autopsy. In all ALS cases there was a marked loss of motor neurons, besides atrophic neurons and preserved neurons with cytoplasmic inclusions, and extensive gliosis. In control cases, the immunoreaction in the cytoplasm of neurons was weak for phosphorylated NF-H, strong for NF-M and weak for NF-L. In ALS cases, anterior horn neurons showed intense immunoreactivity in focal regions of neuronal perikarya for all subunits, although the difference in the integrated optical density was statistically significant only for NF-H. Furthermore, we also observed dilated axons (spheroids), which were immunopositive for NF-H but negative for NF-M and NF-L. In conclusion, we present qualitative and quantitative evidence of NF-H subunit accumulation in neuronal perikarya and spheroids, which suggests a possible role of this subunit in the pathogenesis of ALS.

Hereditary motor and autonomic neuronopathy 1 maps to chromosome 20q13.2-13.3

The spinal muscular atrophies (SMA) or hereditary motor neuronopathies result from the continuous degeneration and death of spinal cord lower motor neurons, leading to progressive muscular weakness and atrophy. We describe a large Brazilian family exhibiting an extremely rare, late-onset, dominant, proximal, and progressive SMA accompanied by very unusual manifestations, such as an abnormal sweating pattern, and gastrointestinal and sexual dysfunctions, suggesting concomitant involvement of the autonomic nervous system. We propose a new disease category for this disorder, `hereditary motor and autonomic neuronopathy', and attribute the term, `survival of motor and autonomic neurons 1' (SMAN1) to the respective locus that was mapped to a 14.5 cM region on chromosome 20q13.2-13.3 by genetic linkage analysis and haplotype studies using microsatellite polymorphic markers. This locus lies between markers D20S120 and D20S173 showing a maximum LOD score of 4.6 at D20S171, defining a region with 33 known genes, including several potential candidates. Identifying the SMAN1 gene should not only improve our understanding of the molecular mechanisms underlying lower motor neuron diseases but also help to clarify the relationship between motor and autonomic neurons.

Arthrogryposis in Murrah buffaloes in southern Brazil

Congenital arthrogryposis is described in a Murrah buffalo herd. The disease was characterized by curvature and multiple articular rigidity of the hindlimbs or of all limbs without associated defects except for one case of brachygnatia. Histologically there was reduction of motor neurons from the ventral horns of the spinal cord and hypoplasia of the limb muscles. Analysis of the herd breeding records suggests that the disease is genetically transmitted by an autosomal recessive trait.

Interaction between affordance and handedness recognition: a chronometric study

The visualization of tools and manipulable objects activates motor-related areas in the cortex, facilitating possible actions toward them. This pattern of activity may underlie the phenomenon of object affordance. Some cortical motor neurons are also covertly activated during the recognition of body parts such as hands. One hypothesis is that different subpopulations of motor neurons in the frontal cortex are activated in each motor program; for example, canonical neurons in the premotor cortex are responsible for the affordance of visual objects, while mirror neurons support motor imagery triggered during handedness recognition. However, the question remains whether these subpopulations work independently. This hypothesis can be tested with a manual reaction time (MRT) task with a priming paradigm to evaluate whether the view of a manipulable object interferes with the motor imagery of the subject's hand. The MRT provides a measure of the course of information processing in the brain and allows indirect evaluation of cognitive processes. Our results suggest that canonical and mirror neurons work together to create a motor plan involving hand movements to facilitate successful object manipulation.

Lesion of the subthalamic nucleus reverses motor deficits but not death of nigrostriatal dopaminergic neurons in a rat 6-hydroxydopamine-lesion model of Parkinson's disease

The objective of the present study was to determine whether lesion of the subthalamic nucleus (STN) promoted by N-methyl-D-aspartate (NMDA) would rescue nigrostriatal dopaminergic neurons after unilateral 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB). Initially, 16 mg 6-OHDA (6-OHDA group) or vehicle (artificial cerebrospinal fluid - aCSF; Sham group) was infused into the right MFB of adult male Wistar rats. Fifteen days after surgery, the 6-OHDA and SHAM groups were randomly subdivided and received ipsilateral injection of either 60 mM NMDA or aCSF in the right STN. Additionally, a control group was not submitted to stereotaxic surgery. Five groups of rats were studied: 6-OHDA/NMDA, 6-OHDA/Sham, Sham/NMDA, Sham/Sham, and Control. Fourteen days after injection of 6-OHDA, rats were submitted to the rotational test induced by apomorphine (0.1 mg/kg, ip) and to the open-field test. The same tests were performed again 14 days after NMDA-induced lesion of the STN. The STN lesion reduced the contralateral turns induced by apomorphine and blocked the progression of motor impairment in the open-field test in 6-OHDA-treated rats. However, lesion of the STN did not prevent the reduction of striatal concentrations of dopamine and metabolites or the number of nigrostriatal dopaminergic neurons after 6-OHDA lesion. Therefore, STN lesion is able to reverse motor deficits after severe 6-OHDA-induced lesion of the nigrostriatal pathway, but does not protect or rescue dopaminergic neurons in the substantia nigra pars compacta.

Serotonergic neurons in the caudal raphe nuclei discharge in association with activity of masticatory muscles

There is a dense serotonergic projection from nucleus raphe pallidus and nucleus raphe obscurus to the trigeminal motor nucleus and serotonin exerts a strong facilitatory action on the trigeminal motoneurons. Some serotonergic neurons in these caudal raphe nuclei increase their discharge during feeding. The objective of the present study was to investigate the possibility that the activity of these serotonergic neurons is related to activity of masticatory muscles. Cats were implanted with microelectrodes and gross electrodes. Caudal raphe single neuron activity, electrocorticographic activity, and splenius, digastric and masseter electromyographic activities were recorded during active behaviors (feeding and grooming), during quiet waking and during sleep. Seven presumed serotonergic neurons were identified. These neurons showed a long duration action potential (>2.0 ms), and discharged slowly (2-7 Hz) and very regularly (interspike interval coefficient of variation <0.3) during quiet waking. The activity of these neurons decreased remarkably during fast wave sleep (78-100%). Six of these neurons showed tonic changes in their activity positively related to digastric and/or masseter muscle activity but not to splenius muscle activity during waking. These data are consistent with the hypothesis that serotonergic neurons in the caudal raphe nuclei play an important role in the control of jaw movements

Selective destruction of nigrostriatal dopaminergic neurons does not alter [3H]-ryanodine binding in rat striatum

Dopamine nigrostriatal neurons are important for motor control and may contain a particularly dense population of ryanodine receptors involved in the control of dopamine release. To test this hypothesis, we used a classical model of unilateral selective lesion of these neurons in rats based on 6-hydroxydopamine (6-OHDA) injection into the substantia nigra. Binding of [3H]-GBR 12935, used as a presynaptic marker since it labels specifically the dopamine uptake complex, was dramatically decreased by 83-100% in striatum homogenates after 6-OHDA lesion. On the contrary, no reduction of [3H]-ryanodine binding was observed. The present data indicate that [3H]-ryanodine binding sites present in rat striatum are not preferentially localized in dopaminergic terminals.

Behavioral correlates of the activity of serotonergic and non-serotonergic neurons in caudal raphe nuclei

We investigated the behavioral correlates of the activity of serotonergic and non-serotonergic neurons in the nucleus raphe pallidus (NRP) and nucleus raphe obscurus (NRO) of unanesthetized and unrestrained cats. The animals were implanted with electrodes for recording single unit activity, parietal oscillographic activity, and splenius, digastric and masseter electromyographic activities. They were tested along the waking-sleep cycle, during sensory stimulation and during drinking behavior. The discharge of the serotonergic neurons decreased progressively from quiet waking to slow wave sleep and to fast wave sleep. Ten different patterns of relative discharge across the three states were observed for the non-serotonergic neurons. Several non-serotonergic neurons showed cyclic discharge fluctuations related to respiration during one, two or all three states. While serotonergic neurons were usually unresponsive to the sensory stimuli used, many non-serotonergic neurons responded to these stimuli. Several non-serotonergic neurons showed a phasic relationship with splenius muscle activity during auditory stimulation. One serotonergic neuron showed a tonic relationship with digastric muscle activity during drinking behavior. A few non-serotonergic neurons exhibited a tonic relationship with digastric and/or masseter muscle activity during this behavior. Many non-serotonergic neurons exhibited a phasic relationship with these muscle activities, also during this behavior. These results suggest that the serotonergic neurons in the NRP and NRO constitute a relatively homogeneous population from a functional point of view, while the non-serotonergic neurons form groups with considerable functional specificity. The data support the idea that the NRP and NRO are implicated in the control of somatic motor output.

The brain decade in debate: VI. Sensory and motor maps: dynamics and plasticity

This article is an edited transcription of a virtual symposium promoted by the Brazilian Society of Neuroscience and Behavior (SBNeC). Although the dynamics of sensory and motor representations have been one of the most studied features of the central nervous system, the actual mechanisms of brain plasticity that underlie the dynamic nature of sensory and motor maps are not entirely unraveled. Our discussion began with the notion that the processing of sensory information depends on many different cortical areas. Some of them are arranged topographically and others have non-topographic (analytical) properties. Besides a sensory component, every cortical area has an efferent output that can be mapped and can influence motor behavior. Although new behaviors might be related to modifications of the sensory or motor representations in a given cortical area, they can also be the result of the acquired ability to make new associations between specific sensory cues and certain movements, a type of learning known as conditioning motor learning. Many types of learning are directly related to the emotional or cognitive context in which a new behavior is acquired. This has been demonstrated by paradigms in which the receptive field properties of cortical neurons are modified when an animal is engaged in a given discrimination task or when a triggering feature is paired with an aversive stimulus. The role of the cholinergic input from the nucleus basalis to the neocortex was also highlighted as one important component of the circuits responsible for the context-dependent changes that can be induced in cortical maps.

Alguns aspectos epidemiológicos da mortalidade por acidentes de trânsito de veículo a motor na Cidade de São Paulo, Brasil

Foram estudadas algumas características dos óbitos por acidentes de trânsito de veículos a motor, no município de São Paulo, ocorridos entre 1.° de janeiro a 31 de dezembro de 1970. Todas as características do falecido e do acidente foram coletadas a partir dos dados registrados nos laudos de necrópsias existentes no Instituto Médico Legal. O estudo evidenciou que a mortalidade por acidentes de veículo a motor é alta, maior no sexo masculino, aumenta com a idade, sendo que o maior coeficiente foi para maiores de 60 anos. A zona da cidade com maior número de acidentes é a zona Sul, existindo áreas (distritos policiais) e vias públicas preferenciais quanto a ocorrência, em todas as 4 zonas do município; a maior ocorrência de acidentes foi aos sábados e domingos; os pedestres compreendem a grande maioria dos falecidos; proporção apreciável dos falecidos recebeu atendimento hospitalar após o acidente. Foram relacionados também o número total de acidentes, vítimas e mortes mostrando que para cada 100 acidentes ocorreram 62,50 vítimas e 5,13 mortes, e para cada 100 vítimas, 18, 22 mortes.

Aspectos epidemiológicos dos acidentes fatais a veículo a motor na cidade do Salvador (Bahia), Brasil

Foi realizado um estudo com o objetivo de descrever certos aspectos epidemiológicos dos acidentes de trânsito de veículo a motor, na cidade do Salvador, Bahia, Brasil, o qual envolveu coleta de informações no Departamento de Trânsito (DETRAN) e no Instituto de Medicina Legal. Ficou demonstrado que os acidentes de trânsito de veículo a motor são mais freqüentes ao fim da tarde e concentram-se, sobretudo, no fim de semana, isto é, sábado e domingo. Motoristas do sexo masculino foram muito mais freqüentemente envolvidos em acidentes de trânsito do que os do sexo feminino. Foi concluído que os acidentes fatais envolvendo pedestres constituem-se importante problema urbano necessitando cuidadosa atenção por parte de educadores e dos serviços públicos responsáveis pelo setor do trânsito. Foi sugerida a necessidade de melhorar e tornar mais uniforme o sistema de notificação e classificação dos acidentes de veículo a motor pelo DETRAN da cidade do Salvador.

Traumatismo crânio-encefálico: diferenças das vítimas pedestres e ocupantes de veículos a motor

OBJETIVO: Caracterizar as diferenças das vítimas com diagnóstico de traumatismo crânio-encefálico envolvidas em diferentes condições, em acidentes de trânsito de veículo a motor e evidenciar indicadores para prevenção e seu atendimento. MÉTODO: Foram analisados os prontuários de todas as vítimas com diagnóstico de trauma crânio-encefálico, assistidas em hospital de referência para atendimento do trauma, entre março e junho de 1993. A população foi de 156 vítimas, sendo 80 pedestres, 50 ocupantes de veículos a motor, exceto de moto e, 26 motociclistas ou passageiros de motos. RESULTADOS E CONCLUSÕES: Os resultados mostraram que a mortalidade entre pedestres foi a mais alta entre os três grupos (25,0%). Os óbitos ocorrem em 19,2% dos ocupantes de motocicleta e 8,0% dos ocupantes de demais veículos a motor. Foram observadas diferenças estatísticas entre os grupos quando a variável gravidade do trauma crânio-encefálico foi analisado. Análise de certas variáveis mostraram importantes diferenças na distribuição dos três grupos.

Oportunidades do ambiente domiciliar para o desenvolvimento motor

OBJETIVO: Avaliar as oportunidades presentes no ambiente domiciliar para o desenvolvimento motor de lactentes. MÉTODOS: Estudo epidemiológico de base populacional, transversal, realizado com 239 lactentes com idade entre três e 18 meses, residentes no município de Juiz de Fora, MG, em 2010. Os participantes foram selecionados por amostragem aleatória estratificada, conglomerada, em múltiplos estágios. Para avaliar a qualidade e quantidade de estímulo motor no ambiente domiciliar foi utilizado o instrumento Affordance in the Home Environment for Motor Development - Infant Scale. Procedeu-se a análise bivariada com aplicação do teste qui-quadrado, seguida de regressão logística multinomial para verificar a associação entre as oportunidades presentes no domicílio e fatores biológicos, comportamentais, demográficos e socioeconômicos. RESULTADOS: As oportunidades de estimulação ambiental foram relativamente baixas. Na análise bivariada, para a faixa etária de três a nove meses, foi encontrada associação com os fatores: ordem de nascimento (p = 0,06), classificação socioeconômica (p = 0,08), renda mensal (p = 0,06) e renda per capita (p = 0,03). No modelo de regressão, prevaleceu a classificação socioeconômica (RC = 7,46; p = 0,03). Para a faixa etária de dez a 18 meses, os fatores associados, na análise bivariada, foram: estado civil materno (p < 0,01), convívio da criança com o pai (p = 0,08), chefe da família (p = 0,04), número de pessoas no domicílio (p = 0,05), escolaridade materna (p < 0,01) e paterna (p < 0,01), classificação socioeconômica (p < 0,01) e renda per capita (p = 0,03). No modelo de regressão, o estado civil materno (RC = 4,83; p = 0,02), escolaridade materna (RC = 0,29; p = 0,03) e paterna (RC = 0,33; p = 0,04) permaneceram associados às oportunidades de estimulação ambiental. CONCLUSÕES: A união estável dos pais, maior escolaridade materna e paterna e maior nível econômico foram os fatores associados às melhores oportunidades de estimulação motora no lar.

Content validity and reliability of test of gross motor development in Chilean children

ABSTRACT OBJECTIVE To validate a Spanish version of the Test of Gross Motor Development (TGMD-2) for the Chilean population. METHODS Descriptive, transversal, non-experimental validity and reliability study. Four translators, three experts and 92 Chilean children, from five to 10 years, students from a primary school in Santiago, Chile, have participated. The Committee of Experts has carried out translation, back-translation and revision processes to determine the translinguistic equivalence and content validity of the test, using the content validity index in 2013. In addition, a pilot implementation was achieved to determine test reliability in Spanish, by using the intraclass correlation coefficient and Bland-Altman method. We evaluated whether the results presented significant differences by replacing the bat with a racket, using T-test. RESULTS We obtained a content validity index higher than 0.80 for language clarity and relevance of the TGMD-2 for children. There were significant differences in the object control subtest when comparing the results with bat and racket. The intraclass correlation coefficient for reliability inter-rater, intra-rater and test-retest reliability was greater than 0.80 in all cases. CONCLUSIONS The TGMD-2 has appropriate content validity to be applied in the Chilean population. The reliability of this test is within the appropriate parameters and its use could be recommended in this population after the establishment of normative data, setting a further precedent for the validation in other Latin American countries.

Chagasic enteropathy

Involvement of the hollow organs of the digestive apparatus can occur in patients in the chronic phase of Chagas' disease. The basic mechanism is destruction of neurons of the enteric nervous system. Whereas megaesophagus and megacolon are the most notable and most extensively studied expressions of the digestive form of Chagas' disease, involvement of the small intestine (Chagasic enteropathy) is less frequent and less known than involvement of the two above mentioned entities. Chagasic enteropathy can be responsible for important clinical and laboratory manifestations resembling those of dyspeptic syndrome, intestinal pseudo-obstruction and bacterial overgrowth in the small intestine. Chagasic enteropathy also involves peculiar functional changes, especially those related to motor activity of the organ and to intestinal absorption of carbohydrates. In practice, the diagnosis is based on radiographic documentation of dilation of visceral segments. Treatment consists of clinical control of the above syndromes and, eventually, appropriate surgical operations.