Increased levels of the CD40:CD40 ligand dyad in the cerebrospinal fluid of rats with vitamin B12(cobalamin)-deficient central neuropathy.
The levels of the soluble (s) CD40:sCD40 ligand (L) dyad, which belongs to the tumor necrosis factor (TNF)-alpha:TNF-alpha-receptor superfamily, are significantly increased in the cerebrospinal fluid (CSF), but not the serum of cobalamin (Cbl)-deficient (Cbl-D) rats. They were normalized or significantly reduced after treatment with Cbl, transforming growth factor-beta1 or S-adenosyl-L-methionine, and the normal myelin ultrastructure of the spinal cord was concomitantly restored. The concomitance of the two beneficial effects of these treatments strongly suggests that the increases in CSF sCD40:sCD40L levels may participate in the pathogenesis of purely myelinolytic Cbl-D central neuropathy in the rat. In keeping with this, an anti-CD40 treatment prevented myelin lesions.
Veber
Daniela
D
Institute of General Pathology and Center of Excellence on Neurodegenerative Diseases, University of Milan, via Mangiagalli 31, 20133 Milano, Italy.
Mutti
Elena
E
Galmozzi
Enrico
E
Cedrola
Sabrina
S
Galbiati
Stefania
S
Morabito
Alberto
A
Tredici
Giovanni
G
La Porta
Caterina A
CA
Scalabrino
Giuseppe
G
D000818:Animals; D019013:CD40 Antigens / Q000097:blood / Q000134:cerebrospinal fluid*; D023201:CD40 Ligand / Q000097:blood / Q000134:cerebrospinal fluid*; D005743:Gastrectomy; D008297:Male; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid* / Q000209:etiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012436:S-Adenosylmethionine / Q000494:pharmacology; D013116:Spinal Cord / Q000737:chemistry / Q000648:ultrastructure; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014806:Vitamin B 12 Deficiency / Q000134:cerebrospinal fluid* / Q000150:complications
D019013:CD40 Antigens; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D023201:CD40 Ligand; D012436:S-Adenosylmethionine