Book contents
- Frontmatter
- Contents
- List of contributors
- Preface
- Part I Basic aspects of neurodegeneration
- 1 Endogenous free radicals and antioxidants in the brain
- 2 Biological oxidants and therapeutic antioxidants
- 3 Mitochondria, metabolic inhibitors and neurodegeneration
- 4 Excitoxicity and excitatory amino acid antagonists in chronic neurodegenerative diseases
- 5 Glutamate transporters
- 6 Calcium binding proteins in selective vulnerability of motor neurons
- 7 Apoptosis in neurodegenerative diseases
- 8 Neurotrophic factors
- 9 Protein misfolding and cellular defense mechanisms in neurodegenerative diseases
- 10 Neurodegenerative disease and the repair of oxidatively damaged DNA
- 11 Compounds acting on ion channels
- 12 The role of nitric oxide and PARP in neuronal cell death
- 13 Copper and zinc in Alzheimer's disease and amyotrophic lateral sclerosis
- 14 The role of inflammation in Alzheimer's disease neuropathology and clinical dementia. From epidemiology to treatment
- 15 Selected genetically engineered models relevant to human neurodegenerative disease
- 16 Toxic animal models
- 17 A genetic outline of the pathways to cell death in Alzheimer's disease, Parkinson's disease, frontal dementias and related disorders
- 18 Neurophysiology of Parkinson's disease, levodopa-induced dyskinesias, dystonia, Huntington's disease and myoclonus
- Part II Neuroimaging in neurodegeneration
- Part III Therapeutic approaches in neurodegeneration
- Normal aging
- Part IV Alzheimer's disease
- Part VI Other Dementias
- Part VII Parkinson's and related movement disorders
- Part VIII Cerebellar degenerations
- Part IX Motor neuron diseases
- Part X Other neurodegenerative diseases
- Index
- References
4 - Excitoxicity and excitatory amino acid antagonists in chronic neurodegenerative diseases
from Part I - Basic aspects of neurodegeneration
Published online by Cambridge University Press: 04 August 2010
- Frontmatter
- Contents
- List of contributors
- Preface
- Part I Basic aspects of neurodegeneration
- 1 Endogenous free radicals and antioxidants in the brain
- 2 Biological oxidants and therapeutic antioxidants
- 3 Mitochondria, metabolic inhibitors and neurodegeneration
- 4 Excitoxicity and excitatory amino acid antagonists in chronic neurodegenerative diseases
- 5 Glutamate transporters
- 6 Calcium binding proteins in selective vulnerability of motor neurons
- 7 Apoptosis in neurodegenerative diseases
- 8 Neurotrophic factors
- 9 Protein misfolding and cellular defense mechanisms in neurodegenerative diseases
- 10 Neurodegenerative disease and the repair of oxidatively damaged DNA
- 11 Compounds acting on ion channels
- 12 The role of nitric oxide and PARP in neuronal cell death
- 13 Copper and zinc in Alzheimer's disease and amyotrophic lateral sclerosis
- 14 The role of inflammation in Alzheimer's disease neuropathology and clinical dementia. From epidemiology to treatment
- 15 Selected genetically engineered models relevant to human neurodegenerative disease
- 16 Toxic animal models
- 17 A genetic outline of the pathways to cell death in Alzheimer's disease, Parkinson's disease, frontal dementias and related disorders
- 18 Neurophysiology of Parkinson's disease, levodopa-induced dyskinesias, dystonia, Huntington's disease and myoclonus
- Part II Neuroimaging in neurodegeneration
- Part III Therapeutic approaches in neurodegeneration
- Normal aging
- Part IV Alzheimer's disease
- Part VI Other Dementias
- Part VII Parkinson's and related movement disorders
- Part VIII Cerebellar degenerations
- Part IX Motor neuron diseases
- Part X Other neurodegenerative diseases
- Index
- References
Summary
Introduction
In 1935 Krebs discovered that the amino acid glutamate increases metabolism in the isolated retina and that it is concentrated in the cerebral gray matter (Krebs, 1935). Hayashi (1952, 1958) first reported on excitatory properties of glutamate on neuronal tissue. Local administration of glutamate on the motor cortex of dogs and primates resulted in motor seizures. Curtis et al. (1959) subsequently demonstrated that glutamate and aspartate, when applied iontophoretically to the cat spinal cord, depolarized neurons. Since the 1960s there has been appreciation of the role of glutamate in the nervous system, and today it is considered the major excitatory neurotransmitter (Fonnum, 1984). It is essential for learning and memory, synaptic plasticity, neuronal survival and, in early development, for proliferation, migration and differentiation of neuronal progenitors and immature neurons (Guerrini et al., 1995; Ikonomidou et al., 1999; Komuro & Rakic, 1993).
Glutamate fulfils its various functions due to its compartmentalization (Fonnum, 1984). The largest pool of glutamate is the metabolic pool. The neuronal pool is located in nerve endings and represents the neurotransmission pool. A separate pool is located in glia and serves the recycling of transmitter glutamate. The smallest glutamate pool is involved in synthesis of the inhibitory neurotransmitter γ-aminobutyric acid (GABA). Glutamate is released from presynaptic terminals by a calcium-dependent mechanism, is removed subsequently by uptake into the surrounding glial cells and aminated to glutamine.
When released into the synaptic cleft, glutamate acts at the postsynaptic site on receptors (Hollmann & Heinemann, 1994; Nakanishi, 1992).
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- Chapter
- Information
- Neurodegenerative DiseasesNeurobiology, Pathogenesis and Therapeutics, pp. 44 - 56Publisher: Cambridge University PressPrint publication year: 2005
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