The Brain N-Acetyl-Aspartate Alterations due to Emotional Stress in Cuprizone-Induced Demyelination: An in vivo Proton Magnetic Resonance Spectroscopy Study at 3T

Stress is considered as an important risk factor in progression and the onset of many disorders [1, 2] such as multiple sclerosis [3]. However, the alterations in the concentration of N-Acetyl-Aspartate (NAA) as a neuronal marker which is uniquely synthesized in neurons by NAA synthase and degrade in oligodendrocyte by aspartoacylase, as a result of demyelination under detrimental effects of stress are not well understood. 24 female Wistar rats (i.e. Groups 1. No-cuprizone (control), 2. No-stress, 3. Emotional stress, 4. Physical stress) were studied. Following repetitive distress induction in stress groups, cuprizone treatment was carried out for 6 weeks in order to induce demyelination in all groups except control ones. Brain relative metabolite concentrations were investigated by single voxel proton magnetic resonance spectroscopy (reporting NAA relative to total creatine (tCr)). According to 1H-MRS, rats in the no-stress group indicated a reduction in NAA/ tCr (p < 0.001) compared to control animals. In contrast, in both stress-exposed groups, NAA/tCr ratios remarkably increased versus the exclusively cuprizone fed animals (p < 0.001) and the control ones (p < 0.001 for emotionally stressed rats and p < 0.05 for physical ones). Findings show that brain susceptibility and changes underlying to emotional stress in the cuprizone model of multiple sclerosis are of greatest importance. It seems that decreased level of NAA is mainly relevant to neuronal mitochondria impairments, while as a result of stress oxidative enhancement due to emotional stress exposure, oligodendrocyte may become the main victim indicated by the increased level of NAA ratio.

Keywords:

Emotional stress , Physical stress , Multiple Sclerosis , Cuprizone , H-MRS