Influence of spatial information on responses of tonically active neurons in the monkey striatum.

Influence of spatial information on responses of tonically active neurons in the monkey striatum. J Neurophysiol 95: 2975\u20132986, 2006. First published February 8, 2006; doi:10.1152/jn.01113.2005. Previous studies have demonstrated that tonically active neurons (TANs) in the primate striatum play an important role in the detection of rewarding events. However, the influence of the spatial features of stimuli or actions required to obtain reward remains unclear. Here, we examined the activity of TANs in the striatum of monkeys trained to make spatially directed movements elicited by visual stimuli presented ipsilaterally or contralaterally to the moving arm. Among 181 neurons responding to the trigger stimulus, 127 (70%) were nonselective for stimulus location and 54 (30%) responded to only one location of the stimulus. Most of the selective responses (63%) occurred when the stimulus was presented contralaterally to the moving arm. To examine whether TAN responses are related to the location of the stimulus or to the direction of the movement, we tested a subset of the trigger-responsive neurons (n 44) in a condition that elicited reaching toward or away from the stimulus. By comparing TAN activity between the two conditions, we found that half of the responses can be interpreted as being related to the location of the stimulus, one quarter to the direction of movement, and one quarter to the context in which stimulus\u2013movement combination occurs. These results demonstrate that TANs are not limited to motivational processing, but may play a role in the processing of spatial attributes of stimulus and/or movement as well. These response properties suggest that TANs are involved in the flexible shifting of motor responses during spatially directed behavior

Effects of TNF receptor blockade on in vitro cell survival and response to negative energy balance in dairy cattle

Abstract Background Associative data and some controlled studies suggest that the inflammatory cytokine tumor necrosis factor (TNF) α can induce fatty liver in dairy cattle. However, research demonstrating that TNFα is a necessary component in the etiology of bovine fatty liver is lacking. The aim of this work was to evaluate whether blocking TNFα signaling with a synthetic cyclic peptide (TNF receptor loop peptide; TRLP) would improve liver metabolic function and reduce triglyceride accumulation during feed restriction. Results Capability of TRLP to inhibit TNFα signaling was confirmed on primary bovine hepatocytes treated with recombinant bovine TNFα and 4 doses of TRLP (0, 1, 10, 50 μmol/L) over 24 h. Next, 4 lactating Holstein cows (parity 1.4 ± 0.5, 433 ± 131 d in milk) in an incomplete Latin rectangle design (3 × 2) were subcutaneously administered with different TRLP doses (0, 1.5, 3.0 mg/kg BW) every 4 h for 24 h, followed by an intravenous injection of TNFα (5 μg/kg BW). Before and for 2 h after TNFα injection, TRLP decreased plasma non-esterified fatty acid (NEFA) concentration (P ≤ 0.05), suggesting an altered metabolic response to inflammation. Finally, 10 non-pregnant, non-lactating Holstein cows (3.9 ± 1.1 yr of age) were randomly assigned to treatments: control (carrier: 57% DMSO in PBS) or TRLP (1.75 mg TRLP /kg BW per day). Treatments were administrated every 4 h for 7 d by subcutaneous injection to feed-restricted cows fed 30% of maintenance energy requirements. Daily blood samples were analyzed for glucose, insulin, β-hydroxybutyrate, NEFA, and haptoglobin concentrations, with no treatment effects detected. On d 7, cows completed a glucose tolerance test (GTT) by i.v. administration of a dextrose bolus (300 mg glucose/kg BW). Glucose, insulin, and NEFA responses failed to demonstrate any significant effect of treatment during the GTT. However, plasma and liver analyses were not indicative of dramatic lipolysis or hepatic lipidosis, suggesting that the feed restriction protocol failed to induce the metabolic state of interest. Injection site inflammation, assessed by a scorer blinded to treatment, was enhanced by TRLP compared to control. Conclusions Although the TRLP inhibited bovine TNFα signaling and altered responses to i.v. administration of TNFα, repeated use over 7 d caused apparent local allergic responses and it failed to alter metabolism during a feed restriction-induced negative energy balance. Although responses to feed restriction seemed atypical in this study, side effects of TRLP argue against its future use as a tool for investigating the role of inflammation in metabolic impacts of negative energy balance

Mechanisms and aging related diseases

Le vieillissement est une perte progressive et inéluctable des capacités fonctionnelles de l’organisme. Des caractéristiques socio-économiques, des facteurs génétiques et le genre influent sur ce processus et en déterminent la complexité. Les mécanismes moléculaires et cellulaires, qui fondent la physiologie du vieillissement et de la longévité, commencent à être mieux élucidés. Souvent ambivalents, ils sont aussi impliqués dans la survenue de nombreuses pathologies liées à l’âge. Certains d’entre-eux (les principaux) sont décrits dans cet article (restriction calorique, séquences télomériques, klotho, Apolipoprotéine E, voie de signalisation mTOR, axe IGF-1/PI3 kinase/insuline, sirtuines, autophagie, radicaux libres, etc.). Une meilleure compréhension de ces mécanismes suscite beaucoup d’espoirs en termes de prévention et de perspectives thérapeutiques. Néanmoins, des dérives éthiques possibles sont redoutées. Le vieillissement est, ainsi, un enjeu sociétal et de santé publique aussi bien dans les pays développés que dans les pays en développement. Le problème de sa prise en charge se posera avec acuité devant l’augmentation de l’espérance de vie et du nombre de personnes âgées dans le monde.Aging is known as a process leading to a progressive and relentless decline of functional capacities. Social, economic, gender and genetic factors are key modulators of its complexity. A better understanding of cellular and molecular mechanisms that underlie aging and life span physiology is slowly but surely occurring. Here, we give a comprehensive synthesis of the main biological mechanisms controlling aging and aging related diseases (caloric restriction, telomeric sequences, Klotho, Apolipoproteine E, mTOR pathway, IGF-1/PI3 kinase/insulin axis, sirtuins, autophagy, free radicals...). Promising hopes in terms of aging prevention and therapeutic perspectives are made in the near future. Nevertheless, general public fear ethical excesses. At all events, aging is becoming a social and public health stake in developed and developing countries. The elderly care management will be a huge issue regarding the enhancement of life span and the growing number of seniors worldwide