Selected biochemical characteristics of the rat mhSOD1(G93A) transgenic model of familial amyotrophic lateral sclerosis (fALS) and the effects of cytidine 5-diphosphocholine (sodium salt, CDPch) treatment

• Autorzy: Chrapusta S.J. , Herbik M.A. , Sulejczak D. , Grieb P.
• Języki publikacji: EN

Abstrakty

EN

Background: Massive expression in rats of the mutated human superoxide dismutase-1 gene (mhSOD1G93A) causes an incurable, fast-progressing fatal illness that is an established model of fALS. We showed earlier that CDPch can slightly but signifi cantly defer the onset of neurologic symptoms and extend life of the carriers. Here we report effects of the drug on some biochemical indices. Methods: Transgenic mhSOD1G93A(+) (Tg+) rats were randomized by gender and litter between study groups. The treatments began on postnatal day (PD) 61, consisted of a daily ip dose of CDPch (0.5 g/kg) or isotonic NaCl, and continued for a preset time or until an arbitrary (the rats were euthanized when unable to feed voluntarily) death point. Untreated Tg+ rats (PD 50ñ60, 94 and 108ñ129) and their Tg-siblings were used for additional controls. After decapitation, blood serum and CNS were harvested and stored at −80°C till analyzed. Results: ANOVA showed signifi cant (P<0.001) age-related elevation of serum immunoreactive mhSOD1 (s-ir-mhSOD1) in NaCl-treated Tg+ rats, signifi cantly (P=0.011) higher s-ir-mhSOD1 level in NaCl-treated terminal stage Tg+ rats than in their CDPch-treated counterparts, and a signifi cant interaction (P=0.02) between these factorsí effects on s-ir-mhSOD1 level; no such effect was found in serum VEGF or spinal cord ir-mhSOD1 level. There was signifi cant (P<0.01) lowering effect of CDPch treatment, a tendency (P=0.09) for agerelated lowering and a tendency (P=0.10) for interaction between these factorsí effects on serum total thiol (sTT) level; post-hoc analysis showed signifi cantly lower sTT level in CDPch-treated terminal stage rats than in their NaCl-treated counterparts. Western blots showed the existence of multiple oligomeric forms of s-ir-mhSOD1 in Tg+ rats.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2009
• Tom: 69
• Numer: 1
• Opis fizyczny: p.88

Twórcy

autor

Chrapusta S.J.

• Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Herbik M.A.

• Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Sulejczak D.

• Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Grieb P.

• Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland