Increased spinal cord NGF levels in rats with cobalamin (vitamin B12) deficiency.
We have recently demonstrated that the neuropathological morphological alterations caused by cobalamin (Cbl) deficiency in the rat central nervous system are related to the vitamin's inability to modulate the synthesis of some neurotoxic and neurotrophic agents in opposite directions. In the present study, we measured nerve growth factor (NGF) levels in the spinal cord (SC) and cerebrospinal fluid (CSF) of rats made Cbl-deficient (Cbl-D) by means of total gastrectomy (TG) or a Cbl-D diet. In both cases, Cbl deficiency increased SC and CSF NGF levels after the appearance of myelinolytic lesions in the SC white matter (SCWM) (i.e. after the second post-TG month), and these changes were normalised by Cbl treatment in the 4-month-totally-gastrectomised (TGX) rats. Intracerebroventricular (i.c.v.) anti-NGF-antibody treatment prevented the onset of the myelinolytic SCWM lesions in the 2-month-TGX rats (i.e. when SC and CSF NGF levels are still normal) and normalised the ultrastructure of the SCWM in the 4-month-TGX rats, which was however worsened by the i.c.v. administration of NGF. These findings demonstrate that: (i) Cbl deficiency increases SC and CSF NGF levels; and (ii) endogenous NGF seems to play a noxious role in the progression of rat Cbl-D central neuropathy.
Scalabrino
Giuseppe
G
Institute of General Pathology, University of Milan, Via Mangiagalli 31, 20133 Milano, Italy. giuseppe.scalabrino@unimi.it
Mutti
Elena
E
Veber
Daniela
D
Aloe
Luigi
L
Corsi
Massimiliano M
MM
Galbiati
Stefania
S
Tredici
Giovanni
G
D000818:Animals; D008297:Male; D009410:Nerve Degeneration / Q000134:cerebrospinal fluid / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D009414:Nerve Growth Factors / Q000134:cerebrospinal fluid / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology*; D014806:Vitamin B 12 Deficiency / Q000134:cerebrospinal fluid / Q000150:complications / Q000378:metabolism* / Q000473:pathology*
D009414:Nerve Growth Factors