Schmidt / Reith Dopamine and Glutamate in Psychiatric Disorders

1. Auflage 2010
ISBN: 978-1-59259-852-6
Verlag: Humana Press
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, 600 Seiten, eBook

An illuminating summary of our current understanding of the interactive role of dopamine and glutamate in psychiatric diseases and the therapeutic strategies and possibilities for future treatment. Among the new ideas presented are hypotheses on the role of dopamine and glutamate in aggression, the glutamate system in anxiety disorders, glutamate and neurodegeneration, and on the origin and progression of Parkinson's disease. Additional chapters offer novel insights into a variety of psychiatric diseases, including ADHD, stress, aggression, addiction, schizophrenia, depression, social phobias, dementias, bulimia, and neurodegenerative diseases like Parkinson's and Alzheimer's diseases. Each chapter summarizes the prevalence and symptoms of the disease and explains the involvement of dopamine and/or glutamate systems using the newer molecular approaches such as transgenic knockout or knockin mice and recent brain imaging techniques.

Zielgruppe

Professional/practitioner

Autoren/Hrsg.

Schmidt, Werner

Reith, Maarten E. A.

Reith, Maarten

Inhaltsverzeichnis

Dopamine.- Dopamine Receptors.- Dopamine Receptor Alternative Splicing.- Glutamate.- Glutamatergic Pathways.- Glutamate Receptors.- Metabotropic Glutamate Receptors.- Schizophrenia.- Dopamine and Schizophrenia.- Glutamate and Schizophrenia and the N-Methyl-d-Aspartate Receptor Hypofunction Hypothesis.- Role of Glycine in Schizophrenia.- Depression.- Dopamine and Depression.- Glutamate and Depression.- Stress and Aggression.- Dopamine, Glutamate, and Aggression.- Anxiety.- Glutamatergic Systems and Anxiety.- Attention Deficit Hyperactivity Disorder.- Dopamine and Glutamate in Attention Deficit Hyperactivity Disorder.- Addiction.- Dopamine-Glutamate Interactions in Reward-Related Incentive Learning.- Sensitization and Relapse.- Glutamatergic Neurotransmission in Sensitization.- Glutamatergic Mechanisms of Drug Relapse.- Neurodegeneration.- Dopamine and Neurodegeneration.- Glutamate and Neurodegeneration.- Parkinson’s Disease.- Presymptomatic and Symptomatic Stages of Intracerebral Inclusion Body Pathology in Idiopathic Parkinson’s Disease.- Dopamine and Glutamate in Parkinson’s Disease.- Dopamine and Glutamate in Motor and Cognitive Symptoms of Parkinson’s Disease.- Huntington’s Disease.- Dopamine and Glutamate in Huntington’s Disease.- Dementias.- Dopaminergic and Glutamatergic Systems in Alzheimer’s Disease.

Leseproben

"IX NEURODEGENERATION (p. 414-416)

18 Dopamine and Neurodegeneration

Gabriele Gille and Peter Riederer

1. INTRODUCTION

Dopamine (DA) is the prevalent catecholaminergic neurotransmitter in the brain and dopaminergic neurons are mainly located in the substantia nigra (SN), the ventral tegmental area (VTA), and arcuate nuclei. They constitute at least three important dopaminergic pathways: the nigro–striatal, the mesocortical–mesolimbic, and the tubero–infundibular system, which are responsible for locomotor movement, motivation and reward, and secretion of pituitary gland hormones, respectively (1,2).

The dysfunction of these systems can lead to neurological, psychological and endocrinological diseases like, e.g., Parkinson’s disease (PD), attention deficit hyperactivity disorder (ADHD), and prolactinoma (3). There is increasing evidence that DA, besides acting as a neurotransmitter, can become neurotoxic at high concentrations or in an oxidative environment. Especially in idiopathic PD, even though the SN is not the only affected region in the brain, the main pathological hallmark is the progressive degeneration of the neuromelanin-containing dopaminergic neurons in the SN pars compacta (SNpc) causing the cardinal symptoms of tremor, rigidity, and bradykinesia. It is believed that the interplay between the high DA content and a local pro-oxidative environment in the SN mutually promote the increase of oxidative stress and thus the degeneration of dopaminergic neurons.

Principally, DA can exert its neurotoxic effects via oxidative and nonoxidative mechanisms: enzymatic and nonenzymatic oxidation of DA yield redox-active compounds like reactive oxygen species (ROS) and DA-quinones/semiquinones. Condensation reactions of DA with carbonyl groups of aldehydes and a-ketoacids generate tetrahydroisoquinolines (TIQs), which are converted into toxic cations by N-methylation. Moreover, DA can be neurotoxic per se without involving oxidative stress. Possible mechanisms of neurotoxicity and molecular events underlying cell death induced by DA will be discussed in this chapter.

2. OXIDATION REACTIONS OF DA

In the striatum the average DA concentration amounts to 65 µM and in dopaminergic nerve endings a concentration as high as 50 µM is reached, even though most of the DA will be stored in synaptic vesicles (4). When pathological conditions lead to an elevated tunover or release of DA from the vesicles, but also during normal aging, DA-driven production of ROS (H2O2, O2 •-, •OH) and toxic quinone species are accumulated and finally may account for neurodegeneration of the dopaminergic system."