Biomedical subjects

Mitsuhiro Yoshioka

Publications and source records attributed to Mitsuhiro Yoshioka.

41 records · Page 3Linked to original sources

PubMed2002

Effects of ibudilast on hippocampal long-term potentiation and passive avoidance responses in rats with transient cerebral ischemia.

The present study evaluated the effects of ibudilast on impaired passive avoidance responses and hippocampal long-term potentiation (LTP) caused by transient cerebral ischemia in rats. The hippocampal nerve cell density was also measured. The latency determined in retention trials of passive avoidance shortened significantly in the 4-vessel occlusion (4VO) group (in which four blood vessels were occluded for 20 min to cause cerebral ischemia). A significant recovery in the latency was observed by administration of ibudilast (10 mg kg (-1)). The population spike amplitude in both the hippocampal CA1 region and perforant path-dentate gyrus synapses was potentiated by tetanus stimulation in the sham-operated group, while in the 4VO group, LTP was significantly inhibited. This inhibition was reversed by administration of ibudilast (10 mg kg (-1)). A marked reduction of cell densities in the CA1 region was observed in the 4VO group compared with the normal group. The nerve cell density in the hippocampal CA1 region was decreased by 20 min of cerebral ischemia. Ibudilast significantly inhibited the reduction of cell densities in a dose-dependent manner. In contrast, the cell density in the dentate gyrus was comparable in the 4VO and normal groups, and no significant changes were observed in the ibudilast groups. These findings suggest that ibudilast might possess neuronally protective properties, i.e. protecting neurons not only from deaths but also from functional damage due to certain cerebral ischemia.

Animals↗

PubMed2002

Alpha4beta2 nicotinic acetylcholine receptor activation ameliorates impairment of spontaneous alternation behavior in stroke-prone spontaneously hypertensive rats, an animal model of attention deficit hyperactivity disorder.

The objective of the present study was to elucidate the role of nicotine in impairment of spontaneous alternation behavior of juvenile stroke-prone spontaneously hypertensive rats (SHRSP), an animal model of attention deficit hyperactivity disorder (ADHD). Spontaneous alternation behavior assessed by a Y-maze task was significantly lower, and total arm entries were significantly higher in SHRSP than in genetic control Wistar-Kyoto rats. Nicotine (0.1-1 mg/kg, s.c.) dose dependently improved the spontaneous alternation deficit without affecting total arm entries in SHRSP. Nicotine-induced (1 mg/kg, s.c.) improvement was significantly abolished by the centrally acting nicotinic acetylcholine receptor (nAChR) antagonist mecamylamine (1 mg/kg, i.p.), but not by peripherally acting hexamethonium (5 mg/kg, i.p.), suggesting that nicotine-induced improvement is mediated via central nAChR. The alpha4beta2 nAChR antagonist dihydro-beta-erythroidine (3-10 mg/kg, i.p.) dose dependently counteracted nicotine-induced improvement of spontaneous alternation in SHRSP, whereas the alpha7 nAChR antagonist methyllycaconitine (3-10 mg/kg, i.p.) did not. In addition, the alpha4beta2 nAChR agonist RJR-2403 (N-methyl-4-(3-pyridinyl)-3-butene-1-amine; 1-10 mg/kg, s.c.) dose dependently and significantly improved the spontaneous alternation deficit. These findings revealed that nicotine improved spontaneous alternation behavior in SHRSP via the activation of alpha4beta2, but not alpha7, nAChR. Thus, the alpha4beta2 nAChR mechanism might be responsible for the spontaneous alternation deficit in juvenile SHRSP, an animal model of ADHD. This evidence indicates the possibility that selective alpha4beta2 nAChR agonists might be useful for treating attentional dysfunction in ADHD.

Animals↗

PubMed2002

NK(1) receptor and its interaction with NMDA receptor in spinal c-fos expression after lower urinary tract irritation.

The role of neurokinin 1 (NK(1)) receptor and possible interaction between NK(1) and N-methyl-D-aspartic acid (NMDA) glutamatergic receptors were investigated on spinal c-fos expression after lower urinary tract irritation with acetic acid infusion in rats. At both levels of the first (L(1)) and sixth lumbar (L(6)) spinal cord, where most of hypogastric nerve and pelvic nerve afferent terminals project, respectively, the selective NK(1) receptor antagonist CP-99,994 dose dependently reduced the total number of c-fos protein (Fos)-positive cells. However, CP-100,263, the enantiomer of CP-99,994 with a very low affinity for NK(1) receptor, did not have any effect on the total number of Fos-positive cells. Coadministration of a low dose (1 mg/kg) of CP-99,994 and NMDA receptor antagonist (MK-801), either of which alone did not affect c-fos expression, significantly inhibited c-fos expression at both levels of the spinal cord. Regarding regional differences, the number of Fos-positive cells decreased significantly at all regions of the L(6) level, but only at the dorsal horn of the L(1) level. These results indicate that NK(1) receptor is involved in spinal c-fos expression after lower urinary tract irritation and that NK(1) and NMDA receptors have a synergistic interaction in the spinal processing of nociceptive input from the lower urinary tract.

Acetic Acid↗

PubMed2002

Serotonin transporters.

The serotonin transporter is most well known as the site of action of the serotonin reuptake inhibitors, which were initially developed as antidepressants, but now are the most widely used agents in the treatment of many additional neuropsychiatric and related disorders. The discovery that the serotonin transporter gene possesses a functional polymorphism within the promoter region led to many studies examining this polymorphism in individuals with different neuropsychiatric disorders. These observations raise the possibility of developing a new class of agents with different therapeutic and side effect profiles than conventional drugs. This overview of recent studies of the serotonin transporters attempts to open new areas for discussion and define concepts not yet comprehensively reviewed.

Amino Acid Sequence↗

PubMed2002

[Science in atherosclerosis].

Ischemic heart disease and cerebral vascular accident are major cause of death in Japan. Development of these diseases is based on atherosclerosis, which would become evident in the middle-aged. Atherosclerosis is a process of aging, because its progression is closely associated with increase in age. Other factors such as smoking, eating habits and obesity are known to facilitate it. Therefore, it is very important for each one of us to learn the risk factors of atherosclerosis and to prevent it by paying attention to our life style. In this citizen joint symposium, we focused on the strategy for treatment and prevention of atherosclerosis by summarizing its mechanisms and consequences. Participation in the symposium could hopefully stimulate our civil activities against atherosclerosis and help promoting our health care in Hokkaido.

Arteriosclerosis↗