Loss of synaptic but not cytoskeletal proteins in the cerebellum of chronic schizophrenics.
The pathobiology of schizophrenia is poorly understood, and many neuroanatomical domains have been considered to underlie the pathophysiology of the disease. There is considerable clinical and neuroradiological evidence to support cerebellar involvement in the schizophrenic illness. We have analysed the changes in synaptic and cytoskeletal proteins in the cerebellum associated with schizophrenia. The cerebellar expression of tau and MAP2 proteins is similar in schizophrenia to that detected in age-matched controls, whereas the level of SNAP-25 is significantly depleted in the schizophrenic cerebellum. Other synaptic proteins, such as synaptophysin and syntaxin, are not affected. This provides evidence that alterations of the cerebellar synaptic network occur in schizophrenia. These changes may influence cerebellar-forebrain connections, especially those with the frontal lobes, and give rise to the cognitive dysmetria that is characteristic of the clinical phenotype in schizophrenia.
Mukaetova-Ladinska
Elizabeta  B
E
Department of Old Age Psychiatry, Institute for the Health of the Elderly, University of Newcastle upon Tyne, Westgate Road, Newcastle upon Tyne NE4 6BE, UK. elizabeta.mukaetova-ladinska@ncl.ac.uk
Hurt
J
J
Honer
W G
WG
Harrington
C R
CR
Wischik
C M
CM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D015536:Down-Regulation / Q000502:physiology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000648:ultrastructure; D050765:Qa-SNARE Proteins; D012559:Schizophrenia / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009435:Synaptic Transmission / Q000502:physiology; D016708:Synaptophysin / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D016875:tau Proteins / Q000378:metabolism
D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050765:Qa-SNARE Proteins; C494208:SNAP25 protein, human; D016708:Synaptophysin; D050825:Synaptosomal-Associated Protein 25; D016875:tau Proteins