NMN: A Potential Savior for Cognitive Function and Neuronal Health During Hypoglycemia

Today's high-calorie consumption coupled with a sedentary lifestyle has strained our metabolic capabilities, leading to a diabetes epidemic. In the United States alone, over 34 million people are affected by diabetes, and a staggering 90% of these cases are of type 2 diabetes. This form of the disease is characterized by the body's resistance to insulin, a crucial hormone responsible for sugar regulation, or its inability to produce sufficient insulin to maintain normal blood sugar levels.

The Emergence of NMN as a Potential Solution

A recent study by Chinese researchers, published in the Brain Research Bulletin, unveiled the potential of nicotinamide mononucleotide (NMN) in enhancing neuronal survival and cognitive function in hypoglycemic rats suffering from brain injury. This significant finding suggests that NMN could be a promising intervention for hypoglycemia-induced brain damage.

The Consequences of Hypoglycemia on Brain Health

Diabetes management often involves insulin therapy, wherein insulin is administered to regulate blood sugar levels. While this intervention successfully mitigates the complications associated with diabetes, it inadvertently escalates the risk of severe hypoglycemia, which can lead to substantial brain injury. 

Upon experiencing severe hypoglycemia, patients are generally administered a treatment to elevate blood sugar levels. However, this reperfusion often triggers secondary injury leading to significant neuronal death. For instance, while healthy rat neurons in the hippocampus (the brain's learning and memory hub) maintain a clear and intact structure, neurons in hypoglycemic rats exhibit severe degeneration, resulting in a noticeable decline in their numbers.

How NMN Shields the Brain During Hypoglycemia

Researchers discovered that NMN administration could diminish neuronal death following severe hypoglycemia. Rats inflicted with the condition who received glucose and NMN injections experienced an 83% reduction in neuronal death compared to those treated with glucose alone. However, when given a chemical that rendered the nicotinamide adenine dinucleotide (NAD+), a byproduct of NMN, inactive, the rats experienced a 449% increase in neuronal death, thereby counteracting the beneficial effects of NMN. This illustrates the crucial role NAD+ plays in safeguarding neurons.

Hypoglycemia triggers the accumulation of reactive oxygen species (ROS), unstable molecules that can inflict damage on cellular DNA. To counteract this damage, the cell initiates a repair pathway that consumes energy molecules and heavily depends on NAD+, the product of NMN and a crucial player in molecular reactions. The depletion of energy molecules and NAD+ typically results in neuronal death and cognitive impairment.

In hypoglycemic rats, NMN treatment not only curtailed ROS accumulation and the initiation of the molecular repair pathway, but it also reinstated the levels of NAD+ and energy molecules. Moreover, NMN administration effectively prevented deficits in spatial learning and memory following severe hypoglycemia.

Confirming NMN’s Benefits: The Water Maze Experiment

Six weeks post-hypoglycemia, researchers presented the rats with a water maze challenge. The speed at which the animals navigated the maze served as an indicator of their cognitive performance. The rats treated with NMN found their way out of the maze faster than those untreated or treated with NMN and the NAD+-inactivating chemical.

Conclusion

Summarily, NMN exhibits a protective role against severe hypoglycemia-induced neuronal damage and associated cognitive impairments. This discovery simulates real-world scenarios wherein patients are administered glucose and a prospective neuroprotective drug during emergency treatment. The findings from this study suggest that NMN may serve as a potent intervention for patients suffering from severe hypoglycemia.

References

Wang X, Hu X, Zhang L, Xu X, Sakurai T. Nicotinamide mononucleotide administration after severe hypoglycemia improves neuronal survival and cognitive function in rats. Brain Res Bull. 2020;160:98-106. doi:10.1016/j.brainresbull.2020.04.022