Alteration of nitric oxide synthase activity in young and aged apolipoprotein E-deficient mice

Impairments in cognitive performance have been observed in aged apolipoprotein E (apoE)-deficient mice, and apoE epsilon 4 allele is a risk factor in Alzheimer's disease (AD). The absence of apoE correlates with diminished antioxidative capacity in animals, and elevated cerebral oxidative stress has been observed in AD individuals carrying the epsilon 4 alleles. Nitric oxide (NO) is a neurosignaling molecule that has significant roles in cognition. NO has also been implicated in neurodegenerative diseases due to its oxidative properties. The current study examined the possible relationship between apoE and nitric oxide synthase (NOS) by comparing hippocampal and cortical NOS activities in wild-type and apoE-knockout mice. Our results showed that apoE deficiency had no effect on NOS activity in these animals; however, aged animals uniformly exhibited significantly higher NOS activity levels. These findings suggest that increased NOS activity may contribute to cognitive impairments in aged wild-type and apoE-knockout mice due to excess accumulation of oxidative damages in areas involved in learning and memory.