Glutamatergic hypothesis of schizophrenia: involvement of Na+/K+-dependent glutamate transport.
Hypothetical model based on deficient glutamatergic neurotransmission caused by hyperactive glutamate transport in astrocytes surrounding excitatory synapses in the prefrontal cortex is examined in relation to the aetiology of schizophrenia. The model is consistent with actions of neuroleptics, such as clozapine, in animal experiments and it is strongly supported by recent findings of increased expression of glutamate transporter GLT in prefrontal cortex of patients with schizophrenia. It is proposed that mechanisms regulating glutamate transport be investigated as potential targets for novel classes of neuroactive compounds with neuroleptic characteristics. Development of new efficient techniques designed specifically for the purpose of studying rapid activity-dependent translocation of glutamate transporters and associated molecules such as Na+, K+-ATPase is essential and should be encouraged.
Nanitsos
Ellas K
EK
Anatomy and Histology, Institute for Biomedical Research and School of Medical Sciences, The University of Sydney, Anderson Stuart Building F 13, Sydney, NSW 2006, Australia.
Nguyen
Khoa T D
KT
St'astný
Frantisek
F
Balcar
Vladimir J
VJ
D000818:Animals; D001692:Biological Transport; D002490:Central Nervous System / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D018377:Neurotransmitter Agents / Q000378:metabolism; D017397:Prefrontal Cortex; D011618:Psychotic Disorders; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism
D050491:Glutamate Plasma Membrane Transport Proteins; D005971:Glutamates; D018377:Neurotransmitter Agents; D005973:Glutamine; D018698:Glutamic Acid; D000254:Sodium-Potassium-Exchanging ATPase