Role of DBI in brain and its posttranslational processing products in normal and abnormal behavior.
Because diazepam binding inhibitor (DBI) and its processing products coexist with gamma-aminobutyric acid (GABA) in several axon terminals, DBI immunoreactivity was measured in the cerebrospinal fluid (CSF) of individuals suffering from various neuropsychiatric disorders, that are believe to be associated with abnormalities of GABAergic transmission. Increased amounts of DBI-like immunoreactivity were found in the CSF of patients suffering from severe depression with a severe anxiety component (Barbaccia, Costa, Ferrero, Guidotti, Roy, Sunderland, Pickar, Paul and Goodwin, 1986). Moreover, the amount of DBI and its processing products was found to be increased in the CSF of patients with hepatic encephalopathy (HE) (Rothstein, McKhann, Guarneri, Barbaccia, Guidotti and Costa, 1989; Guarneri, Berkovich, Guidotti and Costa, 1990). The clinical rating of HE correlated with the extent of the increase in DBI in CSF. Other lines of research suggest that DBI and DBI processing products may be important factors in behavioral adaptation to stress, acting via benzodiazepine (BZD) binding sites, located on mitochondria. DBI and its processing products, ODN and TTN, are present in high concentrations in the hypothalamus and in the amygdala, two areas of the brain that are important in regulating behavioral patterns associated with conflict situations, anxiety and stress. In CSF, the content of DBI changes in association with corticotropin releasing factor (CRF) (Roy, Pickar, Gold, Barbaccia, Guidotti, Costa and Linnoila, 1989). Finally DBI is preferentially concentrated in steroidogenic tissues and cells (adrenal cortical cells, Leydig cells of the testes and glial cells of the brain).(ABSTRACT TRUNCATED AT 250 WORDS)
Guidotti
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Fidia-Georgetown Institute for the Neurosciences, Georgetown University School of Medicine, Washington, DC 20007.
D000595:Amino Acid Sequence; D001921:Brain / Q000502:physiology* / Q000503:physiopathology; D026261:Diazepam Binding Inhibitor; D006801:Humans; D001523:Mental Disorders / Q000503:physiopathology*; D008959:Models, Neurological; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D011963:Receptors, GABA-A / Q000502:physiology*; D012016:Reference Values
D026261:Diazepam Binding Inhibitor; D009479:Neuropeptides; D011963:Receptors, GABA-A