14-3-3 proteins, particularly of the epsilon isoform, are detectable in cerebrospinal fluids of cerebellar diseases in children.
BACKGROUND
Detection of 14-3-3 proteins in cerebrospinal fluid (CSF) is a powerful tool for elucidating the mechanisms of neurological disorders. There have been useful studies on 14-3-3 CSF protein detection in Creutzfeldt-Jakob disease and other neurological disorders, but none on cerebellar diseases.


OBJECTIVE
To elucidate whether 14-3-3 CSF proteins are a sensitive biomarker of cerebellar disruption in children.


METHODS
We examined 14-3-3 CSF proteins by immunoblotting in seven patients with cerebellar disorders: two with acute cerebellitis, two with acute cerebellar ataxia, and three with cerebellar atrophy. We also investigated 14-3-3 CSF proteins in four cases of febrile seizure and three of influenza-related encephalopathy. Isoforms of 14-3-3 proteins were also identified using isoform-specific antibodies.


RESULTS
14-3-3 proteins were detected in CSF of six patients with cerebellar disorders, the exception being one with acute cerebellar ataxia caused by viral infection. Interestingly, only the 14-3-3 ε isoform was detected in two tested patients with cerebellar involvement. Moreover, longitudinal analysis of 14-3-3 CSF proteins in one patient with infantile neuroaxonal dystrophy showed that the 14-3-3 band density proportionally decreased when the cerebellar atrophy gradually progressed. Another CSF derived from a case of febrile seizure showed no 14-3-3 proteins, whereas all those derived from influenza-related encephalopathy demonstrated 14-3-3 CSF proteins with six isoforms.


CONCLUSIONS
This is the first report on 14-3-3 CSF proteins as a significant biomarker of cerebellar disruption, as well as other brain diseases. Since 14-3-3 ε is localized in the molecular layer of cerebellum, the unique detection of 14-3-3 ε may indicate cerebellar involvement in the brain.
Department of Pediatrics, Chiba University Graduate School of Medicine, Chiba, Japan. kfujii@faculty.chiba-u.jp
Katsunori
K
Fujii
Hideki
H
Uchikawa
Yuzo
Y
Tanabe
Taku
T
Omata
Ikuya
I
Nonaka
Yoichi
Y
Kohno
D048948:14-3-3 Proteins / Q000134:cerebrospinal fluid*; D002526:Cerebellar Diseases / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000473:pathology / Q000821:virology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007251:Influenza, Human / Q000134:cerebrospinal fluid / Q000150:complications; D008279:Magnetic Resonance Imaging; D008297:Male; D020033:Protein Isoforms / Q000134:cerebrospinal fluid*
D048948:14-3-3 Proteins; D020033:Protein Isoforms