Koyama Y.,Osaka Ohtani University
Biomolecular Concepts | Year: 2013
In addition to their potent vasoconstriction effects, endothelins (ETs) show multiple actions in various tissues including the brain. The brain contains high levels of ETs, and their production is stimulated in many brain disorders. Accumulating evidence indicates that activation of brain ET receptors is involved in several pathophysiological responses in damaged brains. In this article, the roles of brain ET systems in relation to brain disorders are reviewed. In the acute phase of stroke, prolonged vasospasm of cerebral arteries and brain edema occur, both of which aggravate brain damage. Studies using ET antagonists show that activation of ET A receptors in the brain vascular smooth muscle induces vasospasm after stroke. Brain edema is induced by increased activity of vascular permeability factors, such as vascular endothelial growth factor and matrix metalloproteinases. Activation of ET B receptors stimulates astrocytic production of these permeability factors. Increases in reactive astrocytes are observed in neurodegenerative diseases and in the chronic phase of stroke, where they facilitate the repair of damaged nerve tissues by releasing neurotrophic factors. ETs promote the induction of reactive astrocytes through ET B receptors. ETs also stimulate the production of astrocytic neurotrophic factors. Recent studies have shown high expression of ET B receptors in neural progenitors. Activation of ET B receptors in neural progenitors promotes their proliferation and migration, suggesting roles for ET B receptors in neurogenesis. Much effort has been invested in the pursuit of novel drugs to induce protection or repair of damaged nerve tissues. From these studies, the pharmacological significance of brain ET systems as a possible target of neuroprotective drugs is anticipated.
Takehashi M.,Osaka Ohtani University |
Kanatsu-Shinohara M.,Kyoto University |
Shinohara T.,Kyoto University
Development Growth and Differentiation | Year: 2010
Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis, and are unique tissue-specific stem cells because of their ability to transmit genetic information to offspring. Generation of knockout mice using mouse SSCs became feasible after the successful establishment of protocols for the transplantation and long-term culture of these cells, called germline stem (GS) cells. Furthermore, SSCs can acquire pluripotentiality similar to that of embryonic stem (ES) cells, in addition to their highly differentiated spermatogenic potential. These ES-like cells, called multipotent GS (mGS) cells, are capable of generating knockout mice in a manner similar to that of ES cells. The use of GS and mGS cells for animal transgenesis has added a new dimension to gene-targeting technology using ES cells and somatic cell nuclear transfer, which has limited application. Furthermore, for regenerative medicine purposes, the use of mGS will settle problems such as ethics issues and immunological rejection associated with ES cells, as well as risks of insertional mutagenesis associated with integrated genes into induced pluripotent stem cells. © 2010 Japanese Society of Developmental Biologists.
Katsuki H.,Kumamoto University |
Michinaga S.,Osaka Ohtani University
Vitamins and Hormones | Year: 2012
Non-ergot-type dopamine receptor agonists such as ropinirole are used for treatment of Parkinson disease, but they frequently produce adverse actions characterized by sleepiness and sleep attacks. Because these symptoms are similar to those observed in patients with narcolepsy, a sleep disorder caused by degeneration of hypothalamic orexin neurons, involvement of orexinergic system in the adverse drug actions is suspected. We found that ropinirole and other non-ergot dopamine D 2 receptor agonists cause selective loss of orexin-immunoreactive neurons in organotypic slice culture of rat hypothalamus. The mechanism of this action is considered to involve D 2 receptor-mediated presynaptic suppression of glutamatergic excitatory inputs to orexin neurons because continuous silencing of excitatory activity of orexin neurons can deplete orexin from cell bodies. In addition, Parkinson disease itself may accompany loss of orexin neurons. Disturbance of orexinergic system may play an important role in sleep/arousal dysfunctions under these and other clinical conditions. © 2012 Elsevier Inc..
Yasuda M.,Osaka Ohtani University
Rorschachiana | Year: 2015
Eye movements during the Rorschach Inkblot Method (RIM) were monitored to investigate the existence of location recognition failures that were accompanied by clients' explanations in the inquiry phase. We hypothesized that perceived locations may have differed from actual explained locations if fixations did not occur -and visual attention was diverted to other locations -just before the response in the free association phase. The eye movement data of 29 participants under a Rorschach administration were collected, and 688 responses were obtained. Of these, 195 responses that involved perception of small, specific locations were used to investigate the association between pre-response eye movements and queried locations. Six responses of three participants showed fixations within 3 s before the time of response at locations different from the locations provided in the explanation. Responses made to similar but different locations were indicative of potential failures of location recognition. © 2015 Hogrefe Publishing.
Koyama Y.,Osaka Ohtani University |
Michinaga S.,Osaka Ohtani University
Journal of Pharmacological Sciences | Year: 2012
The receptors for endothelins (ETs) are classified into the ETA and ETB types. ETB receptors are highly expressed in astrocytes, but pharmacological usages of this receptor are not clarified. In this article, recent studies on the pathophysiological roles of astrocytic ETB receptors in the brain are reviewed. The administration of ETB agonists and antagonists in nerve injury models showed that several astrocytic functions are regulated by ETB receptors. The activation of ETB receptors causes morphological alterations and proliferation of cultured astrocytes. Astrocytes produce various bio-active substances that can affect damage to nerve tissues. ETs stimulate the production of neurotrophic factors by astrocytes. This action improves impaired brain functions. On the other hand, the production of matrix metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF), which induce brain edema, also are stimulated by ETs. These findings indicate that astrocytic functions are effectively regulated by modulations of ETB receptors. In brain insults and neurodegenerative diseases, these functions of astrocytes affect the protection and repair of damaged nerve tissues. Thus, astrocytic ETB receptors could be a target for novel types of neuroprotective drugs. © The Japanese Pharmacological Society.