Triheptanoin, an odd-medium-chain triglyceride, impacts brain cognitive function in young and aged mice.

ABSTRACTThe brain aging process triggers cognitive function impairment, such as memory loss and compromised quality of life. Cognitive impairment is based on bioenergetic status, with reduced glucose uptake and metabolism in aged brains. Anaplerotic substrates are reported to promote mitochondrial ATP generation, having been tested in clinical trials for the treatment of neurological disorders and metabolic diseases.Objectives and Methods: To assess whether the improvement in oxidative capacity ameliorates cognitive function in adults (12 weeks), and aged (22-month-old) C57/6BJ mice, they received (1) a ketogenic diet, (2) a ketogenic diet supplemented with the anaplerotic substance, triheptanoin, or (3) a control diet for 12 weeks. Spontaneous alternation and time spent in a previously closed arm in the Y-maze test and time interacting with an unknown object in the novel object recognition test (NORT) were used to evaluate working memory. Acetylcholinesterase (AChE) activity in the prefrontal lobe, brain left hemisphere, and cerebellum was also evaluated. Glucose transporter 3 (GLUT3) expression in the prefrontal lobe was analyzed by western blotting.Results: The ketogenic diet (KD) reduced spontaneous alternation in aged mice, leading to lower AChE activity in the aged prefrontal lobe and cerebellum, and in the parieto-temporal-occipital lobe of adult mice. Furthermore, KD decreased GLUT3 protein expression in the frontal lobe of the adults.Discussion: Supplementation of KD with triheptanoin prevented memory impairment and showed similar values of AChE activity and GLUT3 expression compared to the controls. Our data suggest that triheptanoin has a potential role in the bioenergetic capacity of the brain, improving cognitive function.

Avaliação diagnóstica na síndrome disfunção cognitiva canina / Diagnostic Evaluation of Canine Cognitive Dysfunction Syndrome

O objetivo do presente estudo foi avaliar o questionário observacional e os testes de reatividade como forma de triagem e diagnóstico da disfunção cognitiva em cães idosos. Foram estudados 10 cães acima de sete anos, que apresentavam queixas comportamentais. Foi utilizado questionário que abordava questões comportamentais, como desorientação, atividade, interação socioambiental, alterações no padrão do sono e casa-sujidade. As respostas foram convertidas em pontuações, cujo somatório classificou o cão com disfunção cognitiva canina (DCC), ou borderline (BL), ou sem alterações comportamentais (SAC). Logo depois, foram realizados, em todos os cães, os seguintes testes cognitivos: open field, curiosidade, interação com humano e com espelho. Pela avaliação do questionário, foi determinado que dois cães tinham DCC, três eram BL, cinco eram SAC. Os cães classificados com DCC tinham idade superior aos demais e apresentaram alterações em todos os testes de reatividade, enquanto os cães BL apresentaram alterações em dois testes de reatividade e os SAC não apresentaram alterações. Conclui-se que, com o aumento da expectativa de vida canina, o questionário observacional foi um instrumento de triagem para a identificação dos cães classificados com DCC, BL e SAC, e os testes de reatividade como um método inovador para identificar o verdadeiro estado cognitivo dos pacientes idosos.(AU)

The objective was to evaluate the observational questionnaire and the reactivity tests as a way of screening and diagnosis of cognitive dysfunction in elderly dogs. Ten dogs over seven years of age, with behavioral complaints, were studied. A questionnaire was used that addressed behavioral issues such as disorientation, activity, socioenvironmental interaction, changes in sleep pattern, and house-dirtiness. Responses were converted into scores, which summed the dog with canine cognitive dysfunction (DCC), or Borderline (BL) or without behavioral changes (SAC). Soon after, the following cognitive tests were performed on all dogs: open field, curiosity, interaction with human and with mirror. Through questionnaire evaluation, two dogs had CHD, three were BL, and five were SAC. The dogs classified with DCC were older than the others and presented alterations in all reactivity tests, while the BL dogs presented changes in two reactivity tests and CAD showed no alterations. With the increase in canine life expectancy, the observational questionnaire was a screening instrument for the identification of dogs classified with DCC, BL and SAC and the reactivity tests as an innovative method to identify the true cognitive status of the dogs elderly patients.(AU)

LmrTX, a basic PLA2 (D49) purified from Lachesis muta rhombeata snake venom with enzymatic-related antithrombotic and anticoagulant activity.

A basic phospholipase A2 (LmrTX) isoform was isolated from Lachesis muta rhombeata snake venom and partially characterized. The venom was fractionated by molecular exclusion chromatography in ammonium bicarbonate buffer followed by reverse-phase HPLC on a C-5 Discovery® Bio Wide column. From liquid chromatography-electrospray ionization/mass spectrometry, the molecular mass of LmrTX was measured as 14.277.50 Da. The amino acid sequence showed a high degree of homology between PLA2 LmrTX from L. muta rhombeata and other PLA2 from snake venoms, like CB1 and CB2 from Crotalus durissus terrificus; LmTX-I and LmTX-II from Lachesis muta muta. LmrTX had PLA2 activity in the presence of a synthetic substrate and alkylation of histidine residues significantly inhibited (P < 0.05) the enzymatic activity of LmrTX and its anticoagulant and antithrombotic activity. In this study, we examined the ability of the LmrTX in altering thrombus formation in living mouse, using a photochemically induced arterial thrombosis model. The control animals that did not receive protein injection showed a normal occlusion time, which was around 57 ± 7.8 min. LmrTX, the PLA2 from L. muta rhombeata venom, caused a change in the occlusion time to 99 ± 10 min with doses of 7.5 µg/mice. Additionally, LmrTX showed the anticoagulant activity in vitro and ex vivo and prolonging the time aggregation in wash platelet induced by ADP and Thrombin.

Suplementação de betaglucano a dietas de leitões de 21 a 60 dias de idade / Beta-glucon suplementacion in diets for piglets from 21 to 60 days of age

Realizou-se um experimento com 1.500 leitões distribuídos em delineamento experimental de blocos ao acaso com cinco tratamentos: controle e com suplementação de 60, 120, 180 e 240g de betaglucano por tonelada de dieta. Foram analisadas as variáveis ganho de peso diário, peso final, consumo de dieta diário e conversão alimentar nos períodos de 21 a 35, 21 a 49 e 21 a 60 dias de idade. Houve aumento linear significativo do peso final e do ganho de peso diário de leitões suplementados com betaglucano na dieta dos 21 aos 60 dias de idade. A inclusão de 240g/ton. proporcionou aumento no peso final de 800g, o que corresponde ao aumento de 3,2 por cento em relação aos animais do grupo-controle. O ganho de peso diário foi 4,7 por cento mais alto para o grupo de animais tratados com 240g/ton. Não se observou efeito significativo dos tratamentos sobre: consumo diário de dieta, conversão alimentar, atividade da enzima superóxido dismutase nem sobre a resposta imune.

A total of 1,500 piglets were used in a completely randomized experimental block design to study the effects of beta-glucon level (control, 60, 120, 180, and 240g per ton of diet) on daily weight gain, body weight, daily feed intake and feed: weight gain ratio from 21 to 35, 21 to 49 and from 21 to 60 days of age Positive and significant linear effects of beta-gluton on body weight and daily weight gain of piglets from 21 to 60 days of age were observed. The inclusion of 240g of beta-gluton in diet resulted in 800g increase in body weight which corresponds to 3.25 percent increase in body weight and 4.7 percent increase in daily weight gain in comparison to animals of the control group. No effects of beta-gluton supplementation on feed intake, feed: weight gain ratio and superoxide dismutase enzyme activity or animal immune response were observed.

Changes in the muscle of weanling rats - abstract only

Weanling rats were fed on a low-protein high carbo-hydrate diet. After 4 weeks they were refed on a stock diet containing 18 percentprotein. Measurements were made of the DNA and protein content of the muscle at the end of the depletion period, at various times during recovery and also in control animals growing normally. The diet caused a virtually complete arrest of growth. Body and muscle weight remained constant at the levels reached on weaning. In muscle the ratio of nitrogen to DNA was greatly reduced; this reduction was entirely at the expense of cellular protein. The connective tissue of muscle continued to increase in amount throughout the depletion period. On refeeding in muscle there was evidence of a lag period before the synthesis of new tissue reached its maximum rate. The results tend to support the suggestion that ratio of non-collagen nitrogen to DNA in muscle may be a useful index of the degree of protein depletion. (AU)

The effect of a low-protein diet, and of refeeding, on the composition of liver and muscle in the weanling rat

(1) Fifty-six weanling rats were fed on a low-protein, high-carbohydrate diet designed to simulate that eaten by poor people in Jamaica. After 4 weeks one group was killed and the remainder were rehabilitated on a stock diet containing 18 percent protein. (2) Measurements were made of the protein and deoxyribonucleic-acid content of liver and muscle at the end of the depletion period, at various times during recovery, and also in control animals growing normally. (3) The 'Jamaican' diet caused a virtually complete arrest of growth. Body-weight, liver weight and muscle weight remained constant at the levels reached on weaning. The ratio of nitrogen to DNA was greatly reduced in both liver and muscle. In muscle this reduction occurred entirely at the expense of cellular protein. The connective tissue of muscle continued to increase in amount throughout the depletion period. (4) On refeeding there was a rapid formation of new protein and DNA in the liver, at about twice the rate that obtains during normal growth. In muscle, on the other hand, there was evidence of a lag period before the synthesis of new tissue reached its maximum rate. (5) The bearing of these results on the assessment and treatment of protein malnutrition in human infants is discussed. They tend to support the suggestion previously put forward, that the ratio of non-collagen nitrogen to DNA in muscle may be a useful index of the degree of protein depletion (AU)