記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：PORTLAND PRESS LTD  

We previously developed cardiac ventricle-specific choline acetyltransferase (ChAT) gene-overexpressing transgenic mice (ChAT tgm), i.e. an in vivo model of the cardiac non-neuronal acetylcholine (NNA) system or non-neuronal cardiac cholinergic system (NNCCS). By using this murine model, we determined that this system was responsible for characteristics of resistance to ischaemia, or hypoxia, via the modulation of cellular energy metabolism and angiogenesis. In line with our previous study, neuronal ChAT-immunoreactivity in the ChAT tgm brains was not altered from that in the wild-type (WT) mice brains; in contrast, the ChAT tgm hearts were the organs with the highest expression of the ChAT transgene. ChAT tgm showed specific traits in a central nervous system (CNS) phenotype, including decreased response to restraint stress, less depressive-like and anxiety-like behaviours and anti-convulsive effects, all of which may benefit the heart. These phenotypes, induced by the activation of cardiac NNCCS, were dependent on the vagus nerve, because vagus nerve stimulation (VS) in WT mice also evoked phenotypes similar to those of ChAT tgm, which display higher vagus nerve discharge frequency; in contrast, lateral vagotomy attenuated these traits in ChAT tgm to levels observed in WT mice. Furthermore, ChAT tgm induced several biomarkers of VS responsible for anti-convulsive and anti-depressive-like effects. These results suggest that the augmentation of the NNCCS transduces an effective and beneficial signal to the afferent pathway, which mimics VS. Therefore, the present study supports our hypothesis that activation of the NNCCS modifies CNS to a more stress-resistant state through vagus nerve activity.

DOI： 10.1042/CS20160277

Web of Science

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Urocortin (UCN), a member of the corticotropin-releasing factor (CRF) family, inhibits food intake when it is injected intracerebroventricularly in rats. To explore the site of action of UCN in feeding behavior, we examined the effects of injection of UCN into various hypothalamic nuclei on food and water intake in 24-h fasted rats. Injection of UCN into the ventromedial hypothalamic nucleus (VMH) significantly inhibited food and water intake over 3 h without sedative effect, but no significant effect was observed following injection either into the lateral hypothalamic area, or the paraventricular nucleus of the hypothalamus. To further explore the physiological significance of endogenous UCN of the VMH in feeding behavior, the effect of immunoneutralization of hypothalamic UCN on food intake was examined. Injection of anti-rat UCN rabbit γ-globulin into the bilateral VMH in freely fed rats significantly potentiated food and water intake compared with rats that received normal rabbit γ-globulin. These results suggest that endogenous UCN in the VMH exert inhibitory control on ingestive behavior. (C) 2000 Elsevier Science B.V.

DOI： 10.1016/S0006-8993(99)02378-1

Scopus

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Elsevier Inc.  

The influence of transient forebrain ischemia on behavioral performance, and the effect of intracerebroventricular (i.c.v.) injection of acidic fibroblast growth factor (aFGF) on such ischemia-induced deficits were examined in Mongolian gerbils by assessing learning and memory in two tasks: passive avoidance and Morris water maze. A 5-min period of forebrain ischemia led to learning and memory deficits in both tasks, and also to neuronal death in the hippocampal CA1 region. Continuous i.c.v. infusion of aFGF bilaterally into the lateral ventricules by osmotic minipumps over 2 days before, and 5 days after the ischemia (a total of 3.6 μg/gerbil) largely prevented both the ischemia-induced behavioral deficits and the neuronal death in the hippocampus. These observations suggest that the hippocampus is a critical site for the performance of the two tasks, and that aFGF has a protective effect against such ischemia-induced learning and memory deficits in gerbils. Copyright (C) 1999 Elsevier Science Inc.

DOI： 10.1016/S0031-9384(98)00330-8

Scopus

PubMed

researchmap

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Effects of a pre-training intraperitoneal glucose injection on learning and memory were tested using two tasks: passive avoidance and Morris water maze. In the former task, mice that had received glucose 2 h prior (but not 1, 3, or 5 h prior) to a trial that combined acquisition with passive avoidance of foot shock showed a significantly increased retention latency when tested 24 h later. Thus, this effect was time-dependent, and it was also found to be dose-dependent by further experiment. In contrast, 2-deoxy-D- glucose and fructose had no such effect. In the Morris water maze task, glucose injection 2 or 3 h before a block of trials enhanced the spatial memory performance of mice. These glucose-induced memory-facilitation effects were abolished by an intracerebroventricular injection of anti-acidic fibroblast growth factor antibody 30 min before the glucose injection, suggesting a critical role for endogenous acidic fibroblast growth factor in this facilitatory effect. Furthermore, continuous intracerebroventricular infusion of acidic fibroblast growth factor in rats significantly increased retention latency (when tested repeatedly on successive days using a passive avoidance task). Our earlier studies demonstrated that brain acidic fibroblast growth factor is produced in the ependymal cells of the cerebroventricular system, and is released into the cerebrospinal fluid following either a meal or a (intraperitoneal or intracerebroventricular) glucose injection. This released acidic fibroblast growth factor also diffuses into the brain parenchyma, and is taken up by neurons in the hippocampus, hypothalamus, and elsewhere in the brain some 2 h after the meal or glucose injection. These and the present findings indicate (i) that pre- training glucose injection improves memory performance, and (ii) that acidic fibroblast growth factor, especially by its action within the hippocampus, is involved in this enhancement process.

DOI： 10.1016/S0306-4522(97)00630-1

Scopus

PubMed

researchmap

記述言語：日本語  

researchmap