Analysis of cerebrospinal fluid from patients with psychiatric and neurological disorders by two‐dimensional electrophoresis: Identification of disease‐associated polypeptides as fibrin fragments

Abstract

Two-dimensional electrophoresis (2-DE) of cerebrospinal fluid (CSF) samples--from 347 patients with various psychiatric and neurological disorders--and subsequent silver staining revealed two additional polypeptides (Mr 40,000) in 49% of 111 schizophrenics, 46% of 43 schizoaffective patients, 36% of 41 patients with affective disorders, 43% of 28 patients with multiple sclerosis, but not in 25 patients without neurological symptomatology, nor in 9 patients with Lues, and in only 2 of 25 patients with AIDS. The two polypeptides, as detected by 2-DE, eluted after size exclusion chromatography in fractions containing proteins with Mr greater than 200,000. After 2-DE of CSF samples, enriched by gel chromatography, the polypeptides were immobilized by blotting onto glass-fiber membranes and subjected to N-terminal sequencing. Polypeptide A was identified as beta-chain remnant (beta 2), derived from plasmin cleavage of fibrin(ogen). After size exclusion chromatography, 2-DE, and Western blotting, polypeptide A and B, as well as several other spots, reacted with fibrinogen antibodies, suggesting that the polypeptides are subunits of a fibrin degradation complex.

Towards two‐dimensional electrophoresis mapping of the cerebrospinal fluid proteome from a single individual

“…CSF is less invasive to obtain than brain tissue and it has been shown that changes in the brain, due to disease or injury, can affect the protein content of CSF. Previous studies have used CSF proteome comparisons to study disorders such as schizophrenia [2][3][4], Alzheimer's disease [5][6][7], and Creutzfeldt-Jakob disease [8,9]. In many of these examples, researchers separated the proteins in CSF using two-dimensional gel electrophoresis and then compared the resulting protein spot patterns.…”

Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder

“…This technique has been applied to the limited study of brain tissues, 2,3 and cerebrospinal fluids [4][5][6][7] obtained from individuals with schizophrenia. Recent advances in image analysis, sequencing and other proteinomic techniques allow for the more detailed analysis of protein expression in biological samples.…”

Comparative Proteomics for the Evaluation of Protein Expression and Modifications in Neurodegenerative Diseases

“…3), confirming the hypothesis of a local production by fibrinolytic activity. These types of fragments have also been found in CSF of patients with psychiatric and neurological disorders in the absence of traumatic lesion (Korschenhausen, Hampel, Ackenheil, Penning, & Muller, 1996;Okamoto, Takahashi, Minoura, Fujita, & Yoshimura, 1991;Wildenauer et al, 1991). In these disorders, the presence of the fragment has been thought due to local inflammation and in some cases correlated to the pathological events and to the clinical course (Okamoto et al, 1991;Wildenauer et al, 1991).…”

“…These types of fragments have also been found in CSF of patients with psychiatric and neurological disorders in the absence of traumatic lesion (Korschenhausen, Hampel, Ackenheil, Penning, & Muller, 1996;Okamoto, Takahashi, Minoura, Fujita, & Yoshimura, 1991;Wildenauer et al, 1991). In these disorders, the presence of the fragment has been thought due to local inflammation and in some cases correlated to the pathological events and to the clinical course (Okamoto et al, 1991;Wildenauer et al, 1991). The presence of the fragments in postmortem brain tissue and CSF of schizophrenic patients support that measurements in CSF from patients can reflect changes occurring in the CNS (Korschenhausen et al, 1996;Wildenauer et al, 1991).…”