Resistance to ethanol sensitization is associated with a loss of synaptic plasticity in the hippocampus.

Behavioral sensitization to repeated ethanol (EtOH) exposure induces an increase in locomotor activity in mice. However, not all animals express such sensitization. Although the literature indicated that the hippocampus may play a role in EtOH sensitization, it is not known whether behavioral sensitization to EtOH is associated with preferential changes in bidirectional synaptic plasticity, i.e., LTP and LTD, two markers of learning capabilities that have also been shown to be involved in addictive behavior. In the present study, we examined whether the vulnerability to develop and express behavioral sensitization to EtOH is associated with altered bidirectional synaptic plasticity in the CA1 area of the dorsal hippocampus. For this purpose, we analyzed both LTP and LTD in resistant and sensitized mice during the expression phase, i.e., 7 days after 10 days of repeated EtOH i.p. administration. We found that resistant mice showed a lack of LTD without changes in LTP. The lack of LTD was associated with an increase in GluN2A protein level and was not due to an altered level of neuronal activity, since no difference was observed between the number of c-FOS positive neurons in sensitized and resistant mice. Given that both types of synaptic plasticity signals may have distinct roles in specific learning and behaviors, our results suggest that resistant mice could exhibit different phenotypes in terms of learning/memory and addictive behaviors compared to sensitized ones. Synapse 71:e21899, 2017. © 2016 Wiley Periodicals, Inc.

BDNF regulation under GFAP promoter provides engineered astrocytes as a new approach for long-term protection in Huntington's disease.

Brain-derived neurotrophic factor (BDNF) is the main candidate for neuroprotective therapeutic strategies for Huntington's disease. However, the administration system and the control over the dosage are still important problems to be solved. Here we generated transgenic mice overexpressing BDNF under the promoter of the glial fibrillary acidic protein (GFAP) (pGFAP-BDNF mice). These mice are viable and have a normal phenotype. However, intrastriatal administration of quinolinate increased the number of reactive astrocytes and enhanced the release of BDNF in pGFAP-BDNF mice compared with wild-type mice. Coincidentally, pGFAP-BDNF mice are more resistant to quinolinate than wild-type mice, suggesting a protective effect of astrocyte-derived BDNF. To verify this, we next cultured astrocytes from pGFAP-BDNF and wild-type mice for grafting. Wild-type and pGFAP-BDNF-derived astrocytes behave similarly in nonlesioned mice. However, pGFAP-BDNF-derived astrocytes showed higher levels of BDNF and larger neuroprotective effects than the wild-type ones when quinolinate was injected 30 days after grafting. Interestingly, mice grafted with pGFAP-BDNF astrocytes showed important and sustained behavioral improvements over time after quinolinate administration as compared with mice grafted with wild-type astrocytes. These findings show that astrocytes engineered to release BDNF can constitute a therapeutic approach for Huntington's disease.

[Functional capacity after cardiac transplantation]. / Capacité fonctionnelle après transplantation cardiaque.

Cardiac transplantation has transformed the prognosis of NYHA Class IV severe cardiac failure. However, despite a "new heart", the exercise tolerance of transplanted patients remains poor for a long time. Cardiac denervation which decreases the chronotropic reserve, diastolic left ventricular dysfunction and intrinsic muscular abnormalities related to lack of training and to treatment are the underlying causes.

[Study of representative periods of day-time and night-time levels of blood pressure]. / Recherche de tranches horaires représentatives des niveaux tensionnels diurnes et nycthéméraux.

UNLABELLED: The aim of this study is to assess whether it is possible to shorten ambulatory blood pressure (ABP) monitoring while getting measurements that precisely reflect 24 hours and daytime blood pressure (BP). METHODS: three hundred and thirty six young male subjects aged: 21 +/- 2 y, height: 178 +/- 7 cm, weight, 75 +/- 12 kg, with normal or "borderline" BP (casual BP: 138 +/- 13/79 +/- 8 mmHg) participated in the study. BP was recorded in each, every 15 minutes on 24 hours with a Spacelabs 5200 device. Systolic and diastolic BP on 24-h, during the 9 a.m. - 8 p.m. period (daytime) and BP related to the different subperiods included between 15 minutes and 6 hours were calculated. BP values obtained from the 196 subperiods were correlated with 24-h, daytime ABP and causal BP. Results were classified according to the value of correlation coefficient, slope and intercept of regressions. RESULTS: no subperiod accurately predict 24-h systolic BP (SBP) or diastolic BP (DBP) (the best correlation are established with the subperiods: 7 p.m.-01 a.m. for SBP; r = 0.916, p less than 10(-9), y = 0.76 x + 30; and 06 a.m.-12 a.m. for DBP; r = 0.914, p less than 10(-9), y = 0.87 x + 9). Four 6 hours subperiods sampled between 09 a.m.-3 p.m. and 12 a.m.-6 p.m. predict alike and in a reasonable way the daytime BP (SBP: r = 0.971, p less than 10(-9), y = 0.94 x + 8; r = 0.973, p less than 10(-9), y = 0.91 x + 7. Best correlations with casual BP are moderate (SBP: r = 0.674, DBP: r = 0.588). COMMENTS: BP measurements of subperiods smaller or equal to 6 hours cannot accurately predict the average 24-h BP. This is related mainly to the night-time/daytime BP fluctuations. Daytime BP can be estimated with short-term monitoring but the duration must not be smaller than 6 hours.