Successful and Unsuccessful Brain Aging in Pets: Pathophysiological Mechanisms behind Clinical Signs and Potential Benefits from Palmitoylethanolamide Nutritional Intervention

Abstract

Canine and feline cognitive dysfunction syndrome is a common neurodegenerative disorder of old age and a natural model of human Alzheimer’s disease. With the unavoidable expanding life expectancy, an increasing number of small animals will be affected. Although there is no cure, early detection and intervention are vitally important to delay cognitive decline. Knowledge of cellular and molecular mechanisms underlying disease onset and progression is an equally decisive factor for developing effective approaches. Uncontrolled neuroinflammation, orchestrated in the central nervous system mainly by astrocytes, microglia, and resident mast cells, is currently acknowledged as a hallmark of neurodegeneration. This has prompted scientists to find a way to rebalance the altered crosstalk between these cells. In this context, great emphasis has been given to the role played by the expanded endocannabinoid system, i.e., endocannabinoidome, because of its prominent role in physiological and pathological neuroinflammation. Within the endocannabinoidome, great attention has been paid to palmitoylethanolamide due to its safe and pro-homeostatic effects. The availability of new ultramicronized formulations highly improved the oral bioavailability of palmitoylethanolamide, paving the way to its dietary use. Ultramicronized palmitoylethanolamide has been repeatedly tested in animal models of age-related neurodegeneration with promising results. Data accumulated so far suggest that supplementation with ultramicronized palmitoylethanolamide helps to accomplish successful brain aging.

Palmitoylethanolamide and Related ALIAmides for Small Animal Health: State of the Art

“…Although studies in small animals are still scarce, there is growing evidence that endocannabinoid-like ALIAmides play key roles in the health of different body organs, such as the gastrointestinal tract [ 113 , 114 ] and the nervous system [ 32 , 34 , 37 ], as well as the upper and lower urinary tract [ 115 , 116 , 117 , 118 ] and the musculoskeletal system [ 97 , 119 , 120 ]. In addition, the deep involvement of ALIAmides in obesity-induced metainflammation is becoming increasingly evident [ 69 , 113 , 121 , 122 , 123 ].…”

“…A large body of evidence has been accumulating on the prohomeostatic functions of ALIAmides in several diseases sustained by non-resolving inflammatory and neuroinflammatory responses. The findings have been reviewed by several excellent papers, to which the reader is encouraged to refer [ 3 , 32 , 33 , 34 , 35 , 36 , 37 ]. After addressing a few general key points on ALIAmides, here we will focus exclusively on the main studies performed on small animals.…”

Metabolite profile of raw and cooked pasta from whole wheat grain enriched with Bambara groundnut

“…Some important pharmaceutical compounds such as cardol, 2‐hydroxy‐gamma‐butyrolactone, 3‐furanmethanol, meglumine, cyclopropyl carbinol, palmidrol, and resorcinol were identified in the raw and cooked pasta samples (Table 1) indicating the medicinal properties of the enriched pasta. Cardol, for example, has been reported as an antifilarial metabolite in cashew ( Anacardium occidentale ) (Suresh & Raj, 1990), while palmidrol also known as palmitoylethanolamide has been shown to play a role in exerting neuroprotection and rebalancing neuroinflammation in animals (Scuderi & Golini, 2021). More recently, some authors demonstrated that palmidrol could function as a natural neuroprotector against COVID‐19 inflammation in humans (Roncati et al, 2021).…”

Dietary Betaine Interacts with Very Long Chain n-3 Polyunsaturated Fatty Acids to Influence Fat Metabolism and Circulating Single Carbon Status in the Cat

“…We’ve reported that gut-microbiome active dietary interventions (e.g., resistant starch) can also modulate circulating status of endocannabinoids and N-acylated amino acids in cats [ 19 ]. Since these signaling lipids play important roles in feline physiology [ 46 , 47 , 48 , 49 , 50 ] and increasing evidence indicates they are subject to nutritional modulation [ 48 , 49 ], the current report will aid in determining feline dietary interventions which are appropriate for lifestage or health status that can be benefitted by changes in endocannabinoid and N-acylated amino acid status.…”