Caffeine and NAD+ Improve Motor Neural Integrity of Dissociated Wobbler Cells In Vitro

Abstract

Amyotrophic lateral sclerosis (ALS) is a common degenerative disease of the central nervous system concerning a progressive loss of upper and lower motor neurons. While 5%–10% of patients are diagnosed with the inherited form of the disease, the vast majority of patients suffer from the less characterized sporadic form of ALS (sALS). As the wobbler mouse and the ALS show striking similarities in view of phenotypical attributes, the mouse is rated as an animal model for the disease. Recent investigations show the importance of nicotinamide adenine dinucleotide (NAD+) and its producing enzyme nicotinic acid mononucleotide transferase 2 (Nmnat2) for neurodegeneration as well as for the preservation of health of the neuronal cells. Furthermore, it is newly determined that these molecules show significant downregulations in the spinal cord of wobbler mice in the stable phase of disease development. Here, we were able to prove a positive benefit on affected motor neurons from an additional NAD+ supply as well as an increase in the Nmnat2 level through caffeine treatment in cells in vitro. In addition, first assumptions about the importance of endogenous and exogenous factors that have an influence on the wellbeing of motor nerve cells in the model of ALS can be considered.

Increased ROS‐Dependent Fission of Mitochondria Causes Abnormal Morphology of the Cell Powerhouses in a Murine Model of Amyotrophic Lateral Sclerosis

“…Heterozygous animals were used for breeding. Oxidative Medicine and Cellular Longevity spinal cord cell cultures was performed as described before [26]. In brief, homozygous mice were decapitated at the age of p40 and spinal cords were removed.…”

“…At a cellular level, degeneration of the upper and lower motor neurons, reduced axonal transport, and mitochondrial dysfunction can be observed [24,25]. In the stable stage starting from p40, the symptoms stagnate [26]. Mitochondrial dysfunctions were detected at various time points during wobbler disease.…”

Caffeine as a Factor Influencing the Functioning of the Human Body—Friend or Foe?

“…This prompts not only the search for new therapies, but also for the causes of these ailments more closely. Over the years, caffeine has been investigated as a potential protective or risk factor for psychiatric disorders [ 90 ]. It has already been documented that caffeine intake is associated with depressive symptoms.…”

Effect of Caffeine Consumption on the Risk for Neurological and Psychiatric Disorders: Sex Differences in Human

“…Neurological and psychiatric disorders are not only expensive to treat, but patients have experienced serious stigma, social exclusion, and poor quality of life as a result of their affliction [18]. Over the years, caffeine has been investigated as a potential risk or protective factor for neurological and psychiatric disorders [19]. Some studies have shown that by drinking more than three cups of coffee a day, caffeine reduces the risk of developing AD and PD [20].…”