Decrease in asymmetrical dimethylarginine, an endogenous nitric oxide synthase inhibitor, in cerebrospinal fluid...

Oxidative stress has been implicated in nervous system aging and the pathogenesis of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. However, the effect of asymmetrical dimethylarginine (ADMA) was previously unknown.

We aimed to investigate the significance of nitric oxide (NO)-mediated neuronal death during elderly aging and in ALS. To do so, the concentration of ADMA, an endogenous NO synthase inhibitor in the cerebrospinal fluid (CSF), was determined in neurologically normal controls and in patients with ALS.

There were 20 untreated patients with ALS (M/F, 12/8) and 20 age-matched controls (M/F, 9/11), with a mean age (±SD) of 66.9 ± 9.2 years for patients and 65.1 ± 13.9 years for controls. The concentrations of ADMA and L-arginine (Arg) in the CSF of ALS patients were measured by high-performance liquid chromatography using an electrochemical detector. Control subjects were neurologically normal patients who underwent lumbar spinal anesthesia for minor surgery.

The ADMA concentration significantly decreased with age, whereas the Arg concentration was unaltered. In patients with ALS, the ADMA concentration was significantly decreased compared with controls of a similar age (-52%, p = 0.0001). It significantly decreased with decreasing global functions of ALS (r(s) = -0.74, p < 0.005), whereas the Arg concentration did not change.

These findings suggest that ADMA may play an important role in regulating NO synthesis in the nervous systems of the elderly during aging and in ALS.