We studied the changes in the proteome of CSF (cerebrospinal fluid) in two animal models of Cbl (cobalamin) deficiency: TGX (totally gastrectomized) rats and rats fed a Cbl-D (Cbl-deficient) diet. Two-dimensional PAGE was used to detect qualitative and quantitative variations in proteins in the CSF samples. The peak increase in total CSF protein concentration was observed 4 months after TG (total gastrectomy) and after 6 months of eating a Cbl-D diet. There is a specific increase 4 months after TG in the spots corresponding to α1-antitrypsin and the de novo presence of thiostatin and haptoglobin β. Cbl-replacement treatment in 4-month-TGX rats corrected these alterations in the CSF proteome. However, most of the CSF proteome alterations attenuated in Cbl-untreated 8-month-TGX rats and in rats fed a Cbl-D diet for 16 months. Transthyretin concentration varied slightly in the CSF of both types of Cbl-D rat, whereas the relative abundance of prostaglandin D synthase rose sharply in the CSF of the rats fed a Cbl-D diet for 16 months. We have demonstrated previously that the histological and ultrastructural CNS (central nervous system) damage in both types of Cbl-D rat appears within 2–3 months of Cbl deficiency, and thus appears to precede the alterations in the CSF proteome. The CSF proteome patterns of rats in which phlogosis was induced in or outside the CNS are quite different from those of the CSF of Cbl-D rats. All these findings demonstrate that the alterations in the CSF proteome of Cbl-D rats are specifically linked to Cbl deficiency.
Abbreviations used: APP, acute phase protein; Cbl, cobalamin; Cbl-D, Cbl-deficient; CNS, central nervous system; CSF, cerebrospinal fluid; 2-DE, two-dimensional electrophoresis; DSP, disease-specific protein; EGF, epidermal growth factor; Hp, haptoglobin; i.c.v., intracerebroventricular; i.m., intramuscular; LPS, lipopolysaccharide; α1-MAP, α1-major acute-phase protein; PGDS, prostaglandin D synthase; SCD, subacute combined degeneration; TG, total gastrectomy; TGX, totally gastrectomized; TNF-α, tumour necrosis factor α; TP, turpentine; TTR, transthyretin.