Norio Ogawa

Bio: Norio Ogawa is an academic researcher from Okayama University. The author has contributed to research in topics: Dopaminergic & Stimulation. The author has an hindex of 12, co-authored 23 publications receiving 471 citations.

Levodopa and dopamine agonists in the treatment of Parkinson's disease: advantages and disadvantages.

Abstract: Recent studies have suggested that free radicals play a key role in the progression of Parkinson’s disease (PD). Although levodopa is the most effective therapeutic agent in the treatment of PD and ha

Successful treatment of levodopa-induced neuroleptic malignant syndrome (NMS) and disseminated intravascular coagulation (DIC) in a patient with Parkinson's disease.

Abstract: After 9 years of treatment for Parkinson's disease, a 68-year-old woman developed the complications of neuroleptic malignant syndrome (NMS) and disseminated intravascular coagulation (DIC) while she was still receiving levodopa, bromocriptine and amantadine hydrochloride. The patient displayed a high fever (40 degrees C), impaired consciousness, marked systemic muscle rigidity, tremor and bloody stools. The diagnosis of NMS and DIC was made on the basis of the symptoms and the results of blood serological tests. The antiparkinsonian drugs that had been administered until her admission to our hospital were continued unchanged, while the NMS was treated with dantrolene sodium and the DIC, with nafamostat mesilate. Both of the above-mentioned therapies were effective. The present case is rare in that the patient developed NMS and DIC during treatment and not after the discontinuation of the antiparkinsonian drugs.

Molecular and chemical neuropharmacology of dopamine receptor subtypes

Abstract: In the fields of psychiatry and neurology, the dopaminergic system is one of the most important neurotransmitter systems in the brain. Whereas pharmacological and biochemical studies had initially indicated two subclasses of dopamine receptors (DA-R), recent progress in molecular biology techniques has led to the identification of five distinct genes of DA-Rs (D1-R-D5-R) and splice variants. The gene products are classified into the D1-R family (D1-R and D5-R) and D2-R family (D2-R, D3-R and D4-R) based on their structure and pharmacological features. This review summarizes the structure, localization, function and pharmacology of DA-R subtypes on the basis of knowledge obtained during the past few years. The genes encoding the D1-R family have no intron and the D2-R family genes have introns. The distributions of mRNAs encoding these five DA-R subtypes in the brain were different from their respective receptors. The localization of DA-R subtypes to particular brain regions and specific pharmacological profiles of DA-R subtypes allow new insights to be made into the mechanism of action of DA in the control of psychiatric and motor functions. The availability of detailed information about DA-R subtypes will not only clarify their roles in the brain, but will probably also lead to the development of new therapeutic drugs with more specific actions.

Oxidative stress in Parkinson's disease

Abstract: Oxidative stress contributes to the cascade leading to dopamine cell degeneration in Parkinson's disease (PD). However, oxidative stress is intimately linked to other components of the degenerative process, such as mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity and inflammation. It is therefore difficult to determine whether oxidative stress leads to, or is a consequence of, these events. Oxidative damage to lipids, proteins, and DNA occurs in PD, and toxic products of oxidative damage, such as 4-hydroxynonenal (HNE), can react with proteins to impair cell viability. There is convincing evidence for the involvement of nitric oxide that reacts with superoxide to produce peroxynitrite and ultimately hydroxyl radical production. Recently, altered ubiquitination and degradation of proteins have been implicated as key to dopaminergic cell death in PD. Oxidative stress can impair these processes directly, and products of oxidative damage, such as HNE, can damage the 26S proteasome. Furthermore, impairment of proteasomal function leads to free radical generation and oxidative stress. Oxidative stress occurs in idiopathic PD and products of oxidative damage interfere with cellular function, but these form only part of a cascade, and it is not possible to separate them from other events involved in dopaminergic cell death.

Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils.

Abstract: Neurogenesis in the dentate gyrus of adult rodents is regulated by NMDA receptors, adrenal steroids, environmental stimuli, and seizures. To determine whether ischemia affects neurogenesis, newly divided cells in the dentate gyrus were examined after transient global ischemia in adult gerbils. 5-Bromo-2'-deoxyuridine-5'-monophosphate (BrdU) immunohistochemistry demonstrated a 12-fold increase in cell birth in the dentate subgranular zone 1-2 weeks after 10 min bilateral common carotid artery occlusions. Two minutes of ischemia did not significantly increase BrdU incorporation. Confocal microscopy demonstrated that BrdU immunoreactive cells in the granule cell layer colocalized with neuron-specific markers for neuronal nuclear antigen, microtubule-associated protein-2, and calbindin D28k, indicating that the newly divided cells migrated from the subgranular zone into the granule cell layer and matured into neurons. Newborn cells with a neuronal phenotype were first seen 26 d after ischemia, survived for at least 7 months, were located only in the granule cell layer, and comprised approximately 60% of BrdU-labeled cells in the granule cell layer 6 weeks after ischemia. The increased neurogenesis was not attributable to entorhinal cortical lesions, because no cell loss was detected in this region. Ischemic preconditioning for 2 min, which protects CA1 neurons against subsequent ischemic damage, did not prevent increased neurogenesis in the granule cell layer after a subsequent severe ischemic challenge. Thus, ischemia-induced dentate neurogenesis is not attributable to CA1 neuronal loss. Enhanced neurogenesis in the dentate gyrus may be a compensatory adaptive response to ischemia-associated injury and could promote functional recovery after ischemic hippocampal injury.

The neuropsychology of 3-D space

Abstract: The neuropsychological literature on 3-D spatial interactions is integrated using a model of 4 major behavioral realms: (a) peripersonal (visuomotor operations in near-body space), (b) focal extrapersonal (visual search and object recognition), (c) action extrapersonal (orienting in topographically defined space), and (d) ambient extrapersonal (orienting in earth-fixed space). Each is associated with a distinct cortical network: dorsolateral peripersonal, predominantly ventrolateral focal-extrapersonal, predominantly ventromedial action-extrapersonal, and predominantly dorsomedial ambient-extrapersonal systems. Interactions in 3-D space are also regulated neurochemically with dopaminergic and cholinergic excitation associated with extrapersonal activation and noradrenergic and serotonergic excitation associated with peripersonal activation. This model can help explain the 3-D imbalances in prominant neuropsychological disorders.

Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease.

Abstract: Dopamine (DA)- or L-dihydroxyphenylalanine-(L-DOPA-) induced neurotoxicity is thought to be involved not only in adverse reactions induced by long-term L-DOPA therapy but also in the pathogenesis of Parkinson's disease. Numerous in vitro and in vivo studies concerning DA- or L-DOPA-induced neurotoxicity have been reported in recent decades. The reactive oxygen or nitrogen species generated in the enzymatical oxidation or auto-oxidation of an excess amount of DA induce neuronal damage and/or apoptotic or non-apoptotic cell death; the DA-induced damage is prevented by various intrinsic and extrinsic antioxidants. DA and its metabolites containing two hydroxyl residues exert cytotoxicity in dopaminergic neuronal cells mainly due to the generation of highly reactive DA and DOPA quinones which are dopaminergic neuron-specific cytotoxic molecules. DA and DOPA quinones may irreversibly alter protein function through the formation of 5-cysteinyl-catechols on the proteins. For example, the formation of DA quinone-alpha-synuclein consequently increases cytotoxic protofibrils and the covalent modification of tyrosine hydroxylase by DA quinones. The melanin-synthetic enzyme tyrosinase in the brain may rapidly oxidize excess amounts of cytosolic DA and L-DOPA, thereby preventing slowly progressive cell damage by auto-oxidation of DA, thus maintainng DA levels. Since tyrosinase also possesses catecholamine-synthesizing activity in the absence of tyrosine hydroxylase (TH), the double-edged synthesizing and oxidizing functions of tyrosinase in the dopaminergic system suggest its potential for application in the synthesis of DA, instead of TH in the degeneration of dopaminergic neurons, and in the normalization of abnormal DA turnover in the long-term L-DOPA-treated Parkinson's disease patients.