The Use of Nitrosative Stress Molecules as Potential Diagnostic Biomarkers in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) of still unclear etiology. In recent years, the search for biomarkers facilitating its diagnosis, prognosis, therapy response, and other parameters has gained increasing attention. In this regard, in a previous meta-analysis comprising 22 studies, we found that MS is associated with higher nitrite/nitrate (NOx) levels in the cerebrospinal fluid (CSF) compared to patients with non-inflammatory other neurological diseases (NIOND). However, many of the included studies did not distinguish between the different clinical subtypes of MS, included pre-treated patients, and inclusion criteria varied. As a follow-up to our meta-analysis, we therefore aimed to analyze the serum and CSF NOx levels in clinically well-defined cohorts of treatment-naïve MS patients compared to patients with somatic symptom disorder. To this end, we analyzed the serum and CSF levels of NOx in 117 patients (71 relapsing-remitting (RR) MS, 16 primary progressive (PP) MS, and 30 somatic symptom disorder). We found that RRMS and PPMS patients had higher serum NOx levels compared to somatic symptom disorder patients. This difference remained significant in the subgroup of MRZ-negative RRMS patients. In conclusion, the measurement of NOx in the serum might indeed be a valuable tool in supporting MS diagnosis.

Negative optokinetic afternystagmus in larval zebrafish demonstrates set-point adaptation.

Motor learning is essential to maintain accurate behavioral responses. We used a larval zebrafish model to study ocular motor learning behaviors. During a sustained period of optokinetic stimulation in 5-day-old wild-type zebrafish larvae the slow-phase eye velocity decreased over time. Then interestingly, a long-lasting and robust negative optokinetic afternystagmus (OKAN) was evoked upon light extinction. The slow-phase velocity, the quick-phase frequency, and the decay time constant of the negative OKAN were dependent on the stimulus duration and the adaptation to the preceding optokinetic stimulation. Based on these results, we propose a sensory adaptation process during continued optokinetic stimulation, which, when the stimulus is removed, leads to a negative OKAN as the result of a changed retinal slip velocity set point, and thus, a sensorimotor memory. The pronounced negative OKAN in larval zebrafish not only provides a practical solution to the hitherto unsolved problems of observing negative OKAN, but also, and most importantly, can be readily applied as a powerful model for studying sensorimotor learning and memory in vertebrates.