Fatty Acids: A Safe Tool for Improving Neurodevelopmental Alterations in Down Syndrome?

Abstract

The triplication of chromosome 21 causes Down syndrome (DS), a genetic disorder that is characterized by intellectual disability (ID). The causes of ID start in utero, leading to impairments in neurogenesis, and continue into infancy, leading to impairments in dendritogenesis, spinogenesis, and connectivity. These defects are associated with alterations in mitochondrial and metabolic functions and precocious aging, leading to the early development of Alzheimer’s disease. Intense efforts are currently underway, taking advantage of DS mouse models to discover pharmacotherapies for the neurodevelopmental and cognitive deficits of DS. Many treatments that proved effective in mouse models may raise safety concerns over human use, especially at early life stages. Accumulating evidence shows that fatty acids, which are nutrients present in normal diets, exert numerous positive effects on the brain. Here, we review (i) the knowledge obtained from animal models regarding the effects of fatty acids on the brain, by focusing on alterations that are particularly prominent in DS, and (ii) the progress recently made in a DS mouse model, suggesting that fatty acids may indeed represent a useful treatment for DS. This scenario should prompt the scientific community to further explore the potential benefit of fatty acids for people with DS.

Ameliorative Effect of Omega-3-Rich Fish Diet on the Neurotoxic Effects of Propionic Acid in a Rodent Model of Autism

“…Omega-6 (ω-6) PUFAs, such as arachidonic acid (AA) and linoleic acid (LA), have been thought to be proinflammatory, whereas ω-3 PUFAs are thought to be anti-inflammatory and/or pro-resolving [25]. Since fish is a significant source of omega-3 fatty acids (n-3 FAs), which are found in the membranes of brain tissue as well [26,27], studies are exploring their nutritional value as a major preventive for neurodevelopmental disorders. Moreover, fishery products are advised as dietary sources because eating fish is linked to a decreased risk of vascular brain disease [28].…”

“…Moreover, fishery products are advised as dietary sources because eating fish is linked to a decreased risk of vascular brain disease [28]. Dietary fish are found to decrease fatty acids (n-3 FAs), which are found in the membranes of brain tissue as well [26,27], studies are exploring their nutritional value as a major preventive for neurodevelopmental disorders. Moreover, fishery products are advised as dietary sources because eating fish is linked to a decreased risk of vascular brain disease [28].…”

Oxidative-Stress-Associated Proteostasis Disturbances and Increased DNA Damage in the Hippocampal Granule Cells of the Ts65Dn Model of Down Syndrome

“…Down syndrome (DS) is the most common genetic cause of intellectual disability [ 1 ] produced by a complete or partial triplication of the human chromosome 21 (Hsa21). Although a variety of cognitive domains are compromised in DS, hippocampal-dependent learning and memory are particularly affected because of anatomical and functional alterations present from prenatal stages [ 2 , 3 ]. These brain alterations are aggravated during later life stages, leading to early aging, increased neurodegeneration, further loss of cognitive abilities, and the development of Alzheimer’s disease (AD) neuropathology [ 4 , 5 ].…”