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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.
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 ...
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.
Phencyclidine (also known as PCP or "Angel Dust") and ketamine, both of which block glutamate receptors, are known to cause psychosis at least somewhat resembling schizophrenia, further suggesting that psychosis and perhaps schizophrenia cannot fully be explained in terms of dopamine function, but may also involve other neurotransmitters. [57]
Research on rodents seeking to understand the possible role of prenatal hypoxia in disorders such as schizophrenia has indicated that it can lead to a range of sensorimotor and learning/memory abnormalities. Impairments in motor function and coordination, evident on challenging tasks when the hypoxia was severe enough to cause brain damage ...
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.
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 ...