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The glutamate hypothesis of schizophrenia models the subset of pathologic mechanisms of schizophrenia linked to glutamatergic signaling. The hypothesis was initially based on a set of clinical, neuropathological, and, later, genetic findings pointing at a hypofunction of glutamatergic signaling via NMDA receptors .
The causes of schizophrenia that underlie the development of schizophrenia, a psychiatric disorder, are complex and not clearly understood.A number of hypotheses including the dopamine hypothesis, and the glutamate hypothesis have been put forward in an attempt to explain the link between altered brain function and the symptoms and development of schizophrenia.
The common dopamine and glutamate models proposed are not mutually exclusive; each is seen to have a role in the neurobiology of schizophrenia. [128] The most common model put forward was the dopamine hypothesis of schizophrenia, which attributes psychosis to the mind's faulty interpretation of the misfiring of dopaminergic neurons. [129]
These glutamate receptors are suggested to play a role in modulating gene expression in glial cells, both during the proliferation and differentiation of glial precursor cells in brain development and in mature glial cells. [12] Glutamate receptors serve to facilitate the impact of the neurotransmitter glutamate in the central nervous system.
Glutamate is a prime example of an excitotoxin in the brain, and it is also the major excitatory neurotransmitter in the central nervous system of mammals. [14] During normal conditions, glutamate concentration can be increased up to 1mM in the synaptic cleft, which is rapidly decreased in the lapse of milliseconds. [15]
The NMDA receptor is a glutamate and ion channel protein receptor that is activated when glycine and glutamate bind to it. [5] The receptor is a highly complex and dynamic heteromeric protein that interacts with a multitude of intracellular proteins via three distinct subunits, namely GluN1, GluN2, and GluN3.
It has been proposed that schizophrenia may be due to an increase or a decrease in glutamate signaling, leading to abnormal excitatory signaling in the prefrontal cortex region of the brain. [15] Glutamate release by astrocytes has been linked to the synchrony of neurons in the hippocampus and cortex. A decrease in system Xc- activity may ...
Glutamate is a very major constituent of a wide variety of proteins; consequently it is one of the most abundant amino acids in the human body. [1] Glutamate is formally classified as a non-essential amino acid, because it can be synthesized (in sufficient quantities for health) from α-ketoglutaric acid, which is produced as part of the citric acid cycle by a series of reactions whose ...
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