New Aspects of N-stearoylethanolamine's Neuroprotective Actions in Ageing Rats

During aging, numerous pathological changes occur in the brain, including changes in its lipid composition. This leads to impaired memory and cognitive function. All existing geriatric drugs cause side effects. N-acylethanolamines (NAE) are a class of biologically active lipids that are part of the body's endocannabinoid system and play an important role in the functioning of the central nervous system.

This study aimed to investigate the effects of NAE18:0 N-stearoylethanolamine (NSE) on memory, exploration activity, neuronal state, and lipid composition, choline, acetylcholine content, and acetylcholinesterase (AChE) activity in the brain and blood plasma in 18-month-old aging rats.

All animals were tested using a “New object recognition test” and “Hole board test” to assess rats’ memory and exploration activity. Old rats in the experimental group were orally administered a water suspension of NSE for 10 days. Thin-layer chromatography, ELISA, and mass spectrometry were used.

The use of NSE led to changes in the phospholipid composition and cholesterol content in the frontal cortex and hippocampus, AChE activity, and a slight increase in acetylcholine in the hippocampus and frontal cortex, a decrease in the number of hyperchromic and vacuolated forms of neurons in brain structures, as well as improved memory and exploratory activity in aging rats.

The neuroprotective effect of NSE in aged rats may be due to its influence on fatty acid amide hydrolase (FAAH) activity, modulation of the PPARγ/NF-κB signaling pathway, activation of PPAR receptors and α7 nicotinic acetylcholine receptors, and the ability of NSE to influence the initial stages of inflammation characteristic of old age. These hypotheses require further research in the future.

Thus, the results of this study suggest that NSE has a pronounced neuroprotective and antiamnestic effect in age-related changes in the brain. The use of NSE in old rats leads to an improvement in cognitive functions, as well as to a decrease in the severity of morphofunctional disorders in brain structures, including a decrease in signs of age-related neuronal degeneration. The data obtained confirm the participation of NSE as a component of the endocannabinoid system in regulating the cholinergic system and highlight the prospects for further studies of this compound in correcting age-related neurodegenerative processes.

These results could be used to develop a new geriatric drug, taking into account the absence of known adverse reactions in NSE.