RESUMO
Serine biosynthesis defects are autosomal recessive metabolic disorders resulting from the deficiency of any of the three enzymes involved in de novo serine biosynthesis, specifically phosphoglycerate dehydrogenase (PGDH), phosphoserine aminotransferase (PSAT), and phosphoserine phosphatase (PSP). In this study, we performed metabolomic profiling on 4 children with serine biosynthesis defects; 3 with PGDH deficiency and 1 with PSAT deficiency. The evaluations were performed at baseline and with serine and glycine supplementation. Metabolomic profiling performed at baseline showed low phospholipid species, including glycerophosphocholine, glycerophosphoethanolamine, and sphingomyelin. All children had low serine and glycine as expected. Low glycerophosphocholine compounds were found in 4 children, low glycerophosphoethanolamine compounds in 3 children, and low sphingomyelin species in 2 children. Metabolic profiling with serine and glycine supplementation showed normalization of most of the low phospholipid compounds in the 4 children. Phospholipids are the major component of plasma and intracellular membranes, and phosphatidylcholine is the most abundant phospholipid of all mammalian cell types and subcellular organelles. Phosphatidylcholine is of particular importance for the nervous system, where it is essential for neuronal differentiation. The observed low phosphatidylcholine species in children with serine biosynthesis defects that improved after serine supplementation, supports the role of serine as a significant precursor for phosphatidylcholine. The vital role that phosphatidylcholine has during neuronal differentiation and the pronounced neurological manifestations in serine biosynthesis defects suggest that phosphatidylcholine deficiency occurring secondary to serine deficiency may have a significant contribution to the development of the neurological manifestations in individuals with serine biosynthesis defects.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos/metabolismo , Suplementos Nutricionais , Glicina/administração & dosagem , Microcefalia/metabolismo , Fosfatidilcolinas/metabolismo , Fosfoglicerato Desidrogenase/deficiência , Transtornos Psicomotores/metabolismo , Convulsões/metabolismo , Serina/biossíntese , Transaminases/deficiência , Erros Inatos do Metabolismo dos Carboidratos/sangue , Erros Inatos do Metabolismo dos Carboidratos/dietoterapia , Diferenciação Celular , Criança , Pré-Escolar , Feminino , Glicina/sangue , Humanos , Lactente , Masculino , Metabolômica/métodos , Microcefalia/sangue , Microcefalia/dietoterapia , Neurônios/metabolismo , Fosfoglicerato Desidrogenase/sangue , Fosfoglicerato Desidrogenase/metabolismo , Transtornos Psicomotores/sangue , Transtornos Psicomotores/dietoterapia , Convulsões/sangue , Convulsões/dietoterapia , Serina/administração & dosagem , Serina/sangue , Transaminases/sangue , Transaminases/metabolismoRESUMO
Basal ganglia (BG) circuits orchestrate complex motor behaviors predominantly via inhibitory synaptic outputs. Although these inhibitory BG outputs are known to reduce the excitability of postsynaptic target neurons, precisely how this change impairs motor performance remains poorly understood. Here, we show that optogenetic photostimulation of inhibitory BG inputs from the globus pallidus induces a surge of action potentials in the ventrolateral thalamic (VL) neurons and muscle contractions during the post-inhibitory period. Reduction of the neuronal population with this post-inhibitory rebound firing by knockout of T-type Ca2+ channels or photoinhibition abolishes multiple motor responses induced by the inhibitory BG input. In a low dopamine state, the number of VL neurons showing post-inhibitory firing increases, while reducing the number of active VL neurons via photoinhibition of BG input, effectively prevents Parkinson disease (PD)-like motor symptoms. Thus, BG inhibitory input generates excitatory motor signals in the thalamus and, in excess, promotes PD-like motor abnormalities. VIDEO ABSTRACT.
Assuntos
Globo Pálido/fisiologia , Neurônios Motores/fisiologia , Inibição Neural/fisiologia , Tálamo/fisiologia , Potenciais de Ação/fisiologia , Oxirredutases do Álcool/genética , Animais , Canais de Cálcio Tipo T/genética , Canais de Cálcio Tipo T/fisiologia , Dopamina/metabolismo , Distonia/dietoterapia , Distonia/tratamento farmacológico , Distonia/fisiopatologia , Feminino , Globo Pálido/citologia , Globo Pálido/metabolismo , Levodopa/uso terapêutico , Masculino , Erros Inatos do Metabolismo/dietoterapia , Erros Inatos do Metabolismo/tratamento farmacológico , Erros Inatos do Metabolismo/fisiopatologia , Camundongos , Camundongos Knockout , Contração Muscular/fisiologia , Vias Neurais/fisiologia , Neurônios/fisiologia , Transtornos Psicomotores/dietoterapia , Transtornos Psicomotores/tratamento farmacológico , Transtornos Psicomotores/fisiopatologia , Tálamo/citologiaRESUMO
Creatine monohydrate (Cr) is a dietary supplement known to improve cognitive functions and has positive therapeutic results under various clinical conditions. The aim of this study was to determine the effect of 2 % Cr supplementation on learning, memory formation, neuromuscular coordination, exploratory and locomotory in male albino mice following hypoxic ischemic insult. At postnatal day, 10 male albino mice pups were subjected to right common carotid artery ligation followed by 8 % hypoxia for 25 min. On postnatal day 20, male mice were separated from the litter and divided into two groups on the basis of special diet supplementation. One group was supplemented with 2 % Cr in diet while the other group was raised on ordinary rodent chow for 8 weeks. Behavioral observations were made during rota rod, open field and Morris water maze test for both treatments. It was observed that supplementation with 2 % Cr for 8 weeks following neonatal brain damage resulted in enhanced muscular strength, neuromuscular coordination and improved body weight. In Morris water maze test, it was observed that Cr supplementation significantly improved mean swimming speed and mice on 2 % Cr diet covered more distance but the spatial memory was not improved significantly following hypoxia ischemia encephalopathy (HIE). Open field parameters and percentage of infarct volume remained unaffected following Cr supplementation. We concluded that 2 % dietary Cr supplementation has a potential to improve the muscle strength and body weight in male albino mice following (HIE) and should be considered for the treatment of neurological ailments.
Assuntos
Creatina/administração & dosagem , Suplementos Nutricionais , Hipóxia-Isquemia Encefálica/complicações , Deficiências da Aprendizagem/dietoterapia , Deficiências da Aprendizagem/etiologia , Transtornos Psicomotores/dietoterapia , Animais , Animais Recém-Nascidos , Comportamento Exploratório , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Força Muscular/fisiologia , Transtornos Psicomotores/etiologia , Teste de Desempenho do Rota-RodRESUMO
OBJECTIVES: To assess whether supplementation with antioxidants, folinic acid, or both improves the psychomotor and language development of children with Down's syndrome. DESIGN: Randomised controlled trial with two by two factorial design. SETTING: Children living in the Midlands, Greater London, and the south west of England. PARTICIPANTS: 156 infants aged under 7 months with trisomy 21. INTERVENTION: Daily oral supplementation with antioxidants (selenium 10 mug, zinc 5 mg, vitamin A 0.9 mg, vitamin E 100 mg, and vitamin C 50 mg), folinic acid (0.1 mg), antioxidants and folinic acid combined, or placebo. MAIN OUTCOME MEASURES: Griffiths developmental quotient and an adapted MacArthur communicative development inventory 18 months after starting supplementation; biochemical markers in blood and urine at age 12 months. RESULTS: Children randomised to antioxidant supplements attained similar developmental outcomes to those without antioxidants (mean Griffiths developmental quotient 57.3 v 56.1; adjusted mean difference 1.2 points, 95% confidence interval -2.2 to 4.6). Comparison of children randomised to folinic acid supplements or no folinic acid also showed no significant differences in Griffiths developmental quotient (mean 57.6 v 55.9; adjusted mean difference 1.7, -1.7 to 5.1). No between group differences were seen in the mean numbers of words said or signed: for antioxidants versus none the ratio of means was 0.85 (95% confidence interval 0.6 to 1.2), and for folinic acid versus none it was 1.24 (0.87 to 1.77). No significant differences were found between any of the groups in the biochemical outcomes measured. Adjustment for potential confounders did not appreciably change the results. CONCLUSIONS: This study provides no evidence to support the use of antioxidant or folinic acid supplements in children with Down's syndrome. TRIAL REGISTRATION: Clinical trials NCT00378456.
Assuntos
Antioxidantes/administração & dosagem , Suplementos Nutricionais , Síndrome de Down/dietoterapia , Leucovorina/administração & dosagem , Administração Oral , Deficiências do Desenvolvimento/dietoterapia , Deficiências do Desenvolvimento/enzimologia , Síndrome de Down/enzimologia , Glutationa Peroxidase/metabolismo , Humanos , Lactente , Transtornos da Linguagem/dietoterapia , Transtornos da Linguagem/enzimologia , Cooperação do Paciente , Transtornos Psicomotores/dietoterapia , Transtornos Psicomotores/enzimologia , Superóxido Dismutase/metabolismo , Resultado do TratamentoRESUMO
Prenatal alcohol exposure can disrupt brain development, leading to a variety of behavioral alterations including learning deficits, hyperactivity, and motor dysfunction. We have been investigating the possibility that perinatal choline supplementation may effectively reduce the severity of alcohol's adverse effects on behavioral development. We previously reported that perinatal choline supplementation can ameliorate alcohol-induced learning deficits and hyperactivity in rats exposed to alcohol during development. The present study examined whether perinatal choline supplementation could also reduce the severity of motor deficits induced by alcohol exposure during the third trimester equivalent brain growth spurt. Male neonatal rats were assigned to one of three treatment groups. One group was exposed to alcohol (6.6 g/kg/day) from postnatal days (PD) 4 to 9 via an artificial rearing procedure. Artificially and normally reared control groups were included. One half of subjects from each treatment received daily subcutaneous injections of a choline chloride solution from PD 4 to 30, whereas the other half received saline vehicle injections. On PD 35-37, subjects were tested on a parallel bar motor task, which requires both balance and fine motor coordination. Ethanol-exposed subjects exhibited significant motor impairments compared to both control groups whose performance did not differ significantly from one another. Perinatal choline treatment did not affect motor performance in either ethanol or control subjects. These data indicate that the beneficial effects of perinatal choline supplementation in ethanol-treated subjects are task specific and suggest that choline is more effective in mitigating cognitive deficits compared to motor deficits associated with developmental alcohol exposure.
Assuntos
Depressores do Sistema Nervoso Central/toxicidade , Colina/uso terapêutico , Etanol/toxicidade , Efeitos Tardios da Exposição Pré-Natal , Transtornos Psicomotores/dietoterapia , Análise de Variância , Animais , Animais Recém-Nascidos , Comportamento Animal , Suplementos Nutricionais , Feminino , Masculino , Gravidez , Transtornos Psicomotores/induzido quimicamente , Desempenho Psicomotor/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
Si en cualquier paciente es importante la valoración de su estado nutricional, ésta se hace imprescindible en niños y adolescentes con Trastorno Psicomotor. Se sabe que un déficit de energía, proteínas y micronutrientes, interfiere con el crecimiento, desarrollo y función neuromuscular de niños y adolescentes sanos. En los que padecen trastorno psicomotor es mayor el riesgo de presentar estos déficits, lo cual se convierte en factor de agresión añadido a su estado general que puede tener graves consecuencias. Por su importancia e interés clínico en beneficio de los pacientes con trastorno psicomotor, se presenta este planteamiento de Evaluación Nutricional, que si bien tiene como base los valores estándar para individuos sanos, de edad y sexo similares, aporta algunas especificaciones útiles para la valoración de quienes presentan trastorno psicomotor. Esta evaluación será provechosa, siempre que se realice de modo sistemático y con una periodicidad determinada (AU)