Creatine kinase BB in brain in schizophrenia

Abstract

Creatine kinase (CK) is responsible for the creatine/creatine phosphate level which that is known to alter in the brain of patients with schizophrenia. A comparative estimation of CK enzymatic activity and immunoreactivity of CK BB was carried out in readily soluble extracts from frontal cortex, anterior and posterior cingulate cortex, hippocampus and cerebellum from brains of individuals with schizophrenia versus normal controls. CK activity was determined using a commercial diagnostic kit. CK BB immunoreactivity was evaluated by ECL -immunoblotting using monoclonal antibody. A drastic drop of CK activity and CK BB immunoreactivity was observed in all the examined brain areas in schizophrenia patients compared to controls (p<0.01), with the maximum drop in the cerebellum. The reduction was independent of age, postmortem interval or chlorpromazine equivalent. The decreased level of CK BB in schizophrenia was confirmed by purification of CK BB from brains of patients with schizophrenia and control brains: the yield of the purified enzyme was significantly lower in schizophrenia, wherein molecular masses of CK B-subunits were equal. Possible causes and consequences of the decrease in CK BB level observed in brain of patients with schizophrenia are discussed.

A proteome analysis of the anterior cingulate cortex gray matter in schizophrenia

“…39 A spot corresponding to CK-Mit was not visualized in a sufficient amount of the schizophrenia ACC gray matter gels, in agreement with the literature detailing a reduced level of CK-Mit in post-mortem schizophrenia tissue. 30,42 This data suggest neuronal energy depletion, possibly glutamatergic. Synaptic filling of glutamatergic cells would also be adversely affected by a loss of CK-Mit in the ACC in schizophrenia.…”

“…However, activity of CKB is thought to be reduced in the frontal cortex, anterior and posterior cingulate, hippocampus and cerebellum in schizophrenia. 42 These conflicting data may be due to the location of CKB to subsets of cells 38,39 which are differentially affected in schizophrenia. CK-Mit, located on the membrane of neurons is involved in the generation of ATP 43 and possibly glutamate filling into synaptic vesicles.…”

Mitochondrial Dysfunction and Psychiatric Disorders

“…In this context, it is known that a diminution of creatine kinase activity may potentially impair energy homeostasis, contributing to brain damage [27]. Moreover, creatine kinase inhibition has also been observed in neurodegenerative and mental diseases, such as Alzheimer's disease, schizophrenia [45] and animal models of some inborn errors of metabolism affecting the brain [46]. MacDonald et al [47] presented very interesting results, showing that levels mRNA of creatine kinase are decreased in bipolar disorder patients, especially in the hippocampus.…”

“…Moreover, some evidences suggest changed levels of highenergy phosphates in the cortex of schizophrenic patients [79]. Burbaeva et al [45] also showed that creatine kinase was altered in the brain of patients with schizophrenia, suggesting that this decrease leads to disturbances in brain energy metabolism and is involved in the pathogenesis of this disorder.…”

Generation of the oxidized form protects human brain type creatine kinase against cystine-induced inactivation

“…Previous studies have indicated that BBCK is one of the targets of oxidative stresses induced by dis- eases or toxins. Particularly, BBCK inactivation by cystine and cystine dimethyl ester (CDME) has been observed by in vivo studies [6][7][8][9]21,22], while the other CK isoforms seem not to be affected during the pathogenesis of cystinosis [23]. The in vivo studies suggest that cystine or CDME may affect enzyme activity by the induction of free radicals and lipoperoxidation production, the increase of carbonylation of proteins and the decrease of thiol/disulfide ratio [24].…”