Fatting the brain: a brief of recent research

Abstract

Fatty acids are of paramount importance to all cells, since they provide energy, function as signaling molecules, and sustain structural integrity of cellular membranes. In the nervous system, where fatty acids are found in huge amounts, they participate in its development and maintenance throughout life. Growing evidence strongly indicates that fatty acids in their own right are also implicated in pathological conditions, including neurodegenerative diseases, mental disorders, stroke, and trauma. In this review, we focus on recent studies that demonstrate the relationships between fatty acids and function and dysfunction of the nervous system. Fatty acids stimulate gene expression and neuronal activity, boost synaptogenesis and neurogenesis, and prevent neuroinflammation and apoptosis. By doing so, they promote brain development, ameliorate cognitive functions, serve as anti-depressants and anti-convulsants, bestow protection against traumatic insults, and enhance repairing processes. On the other hand, unbalance between different fatty acid families or excess of some of them generate deleterious side effects, which limit the translatability of successful results in experimental settings into effective therapeutic strategies for humans. Despite these constraints, there exists realistic evidence to consider that nutritional therapies based on fatty acids can be of benefit to several currently incurable nervous system diseases.

Keywords: monounsaturated fatty acid; neurodegenerative disease; neurological disease; peripheral nerve; polyunsaturated fatty acid; saturated fatty acid.

FIGURE 1

Biosynthesis of fatty acids. Medium- to long chain SFAs are successively transformed by the action of elongases (E) into palmitic acid (16:0), which is then either elongated to stearic acid (18:0), and other long chain SFAs, or desaturated, together with stearic acid (18:0), by δ9 desaturase to produce de novo MUFAs of the n-7 and n-9 series, such as palmitoleic acid (16:1) and oleic acid (18:1). In the case of PUFAs, δ6 and δ5 desaturases work cooperatively with elongases to introduce double bonds and extend the aliphatic chain in a successive manner, from ALA (18:3 n-3) to EPA (20:5 n-3) in the n-3 series, and from LA (18:2 n-6) to AA (20:4 n-6) in the n-6 series. Afterward, these end products are further elongated, desaturated, and submitted to peroxisomal β-oxidation (all three steps indicated by OX) to yield DHA (22:6 n-3) and docosapentaenoic acid (22:5 n-6), respectively. Finally, AA (20:4 n-6) is the precursor of potent pro-inflammatory eicosanoids. EPA (20:5 n-3) produces less potent (dashed arrow) eicosanoids and, together with DHA (22:6 n-3), gives rise to docosanoids with anti-inflammatory properties (i.e., resolvins and protectins). GLA, γ-linolenic acid; DHGLA, dihomo-γ-linolenic acid.

FIGURE 2

Multiple effects of fatty acids in the hippocampus. n-3 and n-6 PUFAs exert a variety of positive actions that promote formation, storage and processing of learning and memory in the hippocampus. In contrast, SFAs display rather negative actions. Green arrows indicate stimulatory effects while orange arrows represent inhibitory effects.

FIGURE 3

Conflicting effects of n-3 PUFAs in the nigrostriatal pathway. n-3 PUFAs are commonly endowed with a wide range of helpful effects, as illustrated by the protective benefit that these fatty acids offer to dopaminergic neurons in the nigrostriatal tract against apoptotic and pro-inflammatory cues. However, extreme caution should be exercised since these same PUFAs may not provide complete safety to halt degeneration induced by parkinsonian toxins or even trigger adverse effects, which eventually aggravates the extent of the pathological process.