RESUMO
Spinocerebellar ataxia type 7 (SCA7) is an inherited neurodegenerative disorder characterized by progressive cerebellar ataxia associated with macular degeneration. We recently described one of the largest series of patients with SCA7 that originated from a founder effect in a Mexican population, which allowed us to perform herein the first comprehensive clinical, neurophysiological, and genetic characterization of Mexican patients with SCA7. In this study, 50 patients, categorized into adult or early phenotype, were clinically assessed using standard neurological exams and genotyped using fluorescent PCR and capillary electrophoresis. Patients with SCA7 exhibited the classical phenotype of the disease characterized by cerebellar ataxia and visual loss; however, we reported, for the first time, frontal-executive disorders and altered sensory-motor peripheral neuropathy in these patients. Semiquantitative analysis of ataxia-associated symptoms was performed using Scale for the Assessment and Rating of Ataxia (SARA) and the Brief Ataxia Rating Scale (BARS) scores, while extracerebellar features were measured employing the Inventory of Non-ataxia Symptoms (INAS) scale. Ataxia rating scales confirmed the critical role size of cytosine-adenine-guanine (CAG) repeat size on age at onset and disease severity, while analysis of CAG repeat instability showed that paternal rather than maternal transmission led to greater instability.
Assuntos
Ataxias Espinocerebelares/diagnóstico , Ataxias Espinocerebelares/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Genótipo , Humanos , Masculino , México , Pessoa de Meia-Idade , Testes Neuropsicológicos , Índice de Gravidade de Doença , Ataxias Espinocerebelares/fisiopatologia , Ataxias Espinocerebelares/psicologia , Adulto JovemRESUMO
Spinocerebellar ataxias (SCA) are a heterogeneous group of neurodegenerative disorders. CAG (cytosine-adenine-guanine) trinucleotide repeat expansions in the causative genes have been identified as the cause of different SCA. In this study, we simultaneously genotyped SCA1, SCA2, SCA3, SCA6, and SCA7 applying a fluorescent multiplex polymerase chain reaction assay. We analyzed 10 families with SCA (64 patients) from five different communities of Veracruz, a Mexican southeastern state, and identified 55 patients for SCA7 and 9 for SCA2, but none for SCA1, SCA3, or SCA6. To our knowledge, this sample represents one of the largest series of SCA7 cases reported worldwide. Genotyping of 300 healthy individuals from Mexican population and compiled data from different ethnicities showed discordant results concerning the hypothesis that SCA disease alleles arise by expansion of large normal alleles.
Assuntos
Efeito Fundador , Proteínas do Tecido Nervoso/genética , Ataxias Espinocerebelares/epidemiologia , Ataxias Espinocerebelares/genética , Expansão das Repetições de Trinucleotídeos/genética , Ataxina-7 , Fluorescência , Frequência do Gene , Genótipo , Humanos , México/epidemiologia , Reação em Cadeia da Polimerase Multiplex , PrevalênciaRESUMO
BACKGROUND: We describe two clinical cases and examine the effects of piracetam on the brainstem auditory response in infantile female rhesus monkeys (Macaca mulatta). RESULTS: We found that the interwave intervals show a greater reduction in a 3-year-old rhesus monkey compared to a 1-year-old rhesus monkey. DISCUSSION: In this report, we discuss the significance of these observations.
Assuntos
Potenciais Evocados Auditivos do Tronco Encefálico/efeitos dos fármacos , Macaca mulatta , Nootrópicos/farmacologia , Piracetam/farmacologia , Anestesia , Animais , FemininoRESUMO
Our aim was to study the specific role of the postsynaptic D(1) receptors on dopaminergic response and analyze the metabolized dopamine (DA) in the rat striatum. We used male Wistar rats to evaluate the effects of different doses of a D(1) agonist (SKF-38393) and a D(1) antagonist (SCH-23390), and their co-administration. The levels of DA and L-3, 4-dihydroxyphenylacetic acid (DOPAC) were measured using high performance liquid chromatography. The systemic injection of SKF-38393 alone at 1, 5 and 10 mg/kg did not alter the DA and DOPAC levels or the DOPAC/DA ratio. In contrast, injection of SCH-23390 alone at 0.25, 0.5 and 1 mg/kg significantly increased the DA and DOPAC levels, as well as the DOPAC/DA ratio, compared with the respective control groups. The co-administration of SCH-23390+SKF-38393 did not alter the DA or DOPAC levels, but it did significantly inhibit the SCH-23390-induced increase of the DA and DOPAC levels. The SCH-23390+SKF-38393 and the SCH-23390-only groups showed an increase in the DOPAC/DA ratio. The co-administration of SCH-23390+PARGYLINE significantly decreased the DOPAC levels and the DOPAC/DA ratio compared with the control and SCH-23390 groups. Taken together, our results showed that selective inhibition with SCH-23390 produced an increase in metabolized DA via striatal monoamine oxidase. These findings also contribute to the understanding of the role of postsynaptic D(1) receptors in the long-loop negative feedback system in the rat striatum.
Assuntos
Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Receptores de Dopamina D1/antagonistas & inibidores , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/administração & dosagem , 2,3,4,5-Tetra-Hidro-7,8-Di-Hidroxi-1-Fenil-1H-3-Benzazepina/farmacologia , Animais , Benzazepinas/administração & dosagem , Benzazepinas/farmacologia , Corpo Estriado/metabolismo , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Masculino , Pargilina/administração & dosagem , Ratos , Ratos WistarRESUMO
INTRODUCTION: The basal ganglia include the striatum, globus pallidus, the substantia nigra pars compacta and pars reticulata. The striatum receives afferent input from the substantia nigra pars compacta. The principal neurons of the striatum are medium spiny neurons, that express high levels of D1 and D2 receptors. AIMS: This review deals about the aspects underlying to the negative feedback via long-loop in the striatal dopamine release modulation in the rat. Also, the motor function in dopamine receptor knock-out mice is discussed. DEVELOPMENT AND CONCLUSIONS: The intrastriatal infusion and systemic injection of dopamine receptor agonists and antagonists may regulate the striatal dopamine release and induce changes in motor function. Disruption of the D1 and D2 gene shown that the motor function is controlled by D1 and D2 receptors. The study of the long-loop negative feedback may contribute to our understanding in the physiology and dysfunction of basal ganglia.
Assuntos
Corpo Estriado/metabolismo , Dopamina/metabolismo , Retroalimentação Fisiológica/fisiologia , Vias Neurais/fisiologia , Animais , Corpo Estriado/citologia , Agonistas de Dopamina/metabolismo , Antagonistas de Dopamina/metabolismo , Globo Pálido/citologia , Globo Pálido/metabolismo , Atividade Motora/fisiologia , Vias Neurais/anatomia & histologia , Neurônios/citologia , Neurônios/metabolismo , Ratos , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Substância Negra/citologia , Substância Negra/metabolismoRESUMO
INTRODUCTION: The cortical ablation has been used as an experimental model in order to study the basic mechanisms of functional recovery. However, there is not data concerning to the injury effects on the motor and somatosensorial behavioral manifestations that allow us to categorize such sequels as a hemiplegic model. MATERIALS AND METHODS: We used 35 male Wistar rats (280-300 g) allocated in two groups: control (n = 17) and brain injured by cortical ablation (n = 18). Previously trained, basal recordings of the footprint and motor and somatosensorial assessment were performed in the rats before surgery. The behavioral tests were performed again 6 hours after surgery and the spontaneous ambulatory activity was also evaluated. RESULTS AND CONCLUSIONS: It was observed a decrease in the stride's length and an increase in the stride's angle and in the motor deficit, while the somatosensorial assessment and spontaneous ambulatory activity were not affected. These findings are discussed in function of the motor features of the hemiparetic sequels in humans.
Assuntos
Comportamento Animal/fisiologia , Córtex Cerebral/patologia , Atividade Motora/fisiologia , Animais , Lesões Encefálicas/fisiopatologia , Córtex Cerebral/fisiologia , Masculino , Desempenho Psicomotor , Ratos , Ratos Wistar , Recuperação de Função FisiológicaRESUMO
We studied the effects of high doses of pentobarbital (PB) and carbamazepine (CBZ) on electrolyte levels and pH in an epileptic animal model. Pentobarbital decreased Ca2+ and Na+ levels without pentylenetetrazole (PTZ). After this, Ca2+ and Na+ levels continued to decrease except when CBZ was used, which preserved the Ca2+ levels PTZ may have opposed effects on PB. Our results suggest that PB causes changes in electrolyte levels and pH, but these changes are diminished by CBZ.