Docosahexaenoic acid and arachidonic acid are fundamental supplements for the induction of neuronal differentiation

Kan, Inna; Melamed, Eldad; Offen, Daniel; Green, Pnina

doi:10.1194/jlr.c600022-jlr200

Cited by 57 publications

(34 citation statements)

References 15 publications

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“…4). These results are consistent with the observations showing that DHA enhances the differentiation of neural stem cells into mature neuronal cells (13,(17)(18)(19). These data together support the notion that DHA is a key element for neurogenesis and neuritogenesis.…”

Section: Discussionsupporting

confidence: 92%

Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid

He¹,

Qu²,

Cui

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

210

141

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Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LC-PUFA), highly enriched in the central nervous system, is critical for brain development and function. It has been shown that DHA deficiency impairs cognitive performance whereas DHA supplementation improves the condition. However, the mechanisms underlying the role of DHA in brain development and function remain to be elucidated. By using transgenic fat-1 mice rich in endogenous n-3 PUFA, we show that increased brain DHA significantly enhances hippocampal neurogenesis shown by an increased number of proliferating neurons and neuritogenesis, evidenced by increased density of dendritic spines of CA1 pyramidal neurons in the hippocampus. Concurrently, fat-1 mice exhibit a better spatial learning performance in the Morris water maze compared with control WT littermates. In vitro experiments further demonstrate that DHA promotes differentiation and neurite outgrowth of neuronal cells derived from mouse ES cells and increases the proliferation of cells undergoing differentiation into neuronal lineages from the ES cells. These results together provide direct evidence for a promoting effect of DHA on neurogenesis and neuritogenesis and suggest that this effect may be a mechanism underlying its beneficial effect on behavioral performance.cognitive function ͉ omega-3 fatty acids ͉ transgenic fat-1 mice ͉ neural stem cells D ocosahexaenoic acid (22:6n-3, DHA) is an omega-3 (n-3) long chain polyunsaturated fatty acid (LC-PUFA) that is highly enriched in the central nervous system, particularly in the synaptosomal membrane, synaptic vesicles, growth cones, and the retina photoreceptors (1). DHA serves not only as a building block for neural development, but also as a functional molecule to maintain proper fluidity of neuronal membranes and modulate neurochemical, gene expression, and memory processes (2). Clinical evidence indicates that term infants given formula supplemented with either DHA plus arachidonic acid or DHA alone have substantially better visual acuity (3) and improved cognitive ability (4). Animal studies revealed that deficiency of DHA resulted in a poorer performance on cognitive and behavioral tests whereas supplementation with DHA led to recovery of learning and memory-related performance (5). Furthermore, neurodegeneration and neuropsychiatric disorders are related to a low level of DHA, and supplementation with DHA ameliorated the symptoms (6). These studies suggest that DHA plays a key role in the development and function of the central nervous system. However, the mechanisms underlying the effects of DHA on brain development and function remain to be elucidated.The dentate gyrus (DG) has been an intensively investigated area of the hippocampus because DG is one of the few brain regions where neurogenesis takes place throughout the life span of mammals and where new memories are formed (7). In addition, DG is critical for normal cognitive function, and dysfunctions in this region are linked to diverse clinical conditions (e.g.,...

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Section: Discussionsupporting

confidence: 92%

Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid

He¹,

Qu²,

Cui

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

210

141

View full text Add to dashboard Cite

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“…DHA is one of the major building structures of membrane phospholipids; its deficiency can prevent proper renewal of membranes and accelerate aging. DHA has been shown to exert positive effects on neuronal differentiation, function, and neurotransmission (4,25,26). Given the low levels of DHA detected in our primary neuronal cultures, in-depth behavioral analysis directed at exploring higher cognitive functions of ABCD2 knockouts seems appropriate.…”

Section: Discussionmentioning

confidence: 99%

A key role for the peroxisomalABCD2transporter in fatty acid homeostasis

Fourcade¹,

Ruíz²,

Camps³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

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“…The application of retinoic acid as a caudalizing factor 55 and sonic hedgehog as a ventralizing factor 71 to age-appropriate embryonic cells can be used to preferentially differentiate this pluripotent cell type into a terminally differentiated motoneuron. Enhancement of neurite outgrowth has been extensively studied in vitro and is affected by a variety of substances such as cAMP analogs, 48,114 fatty acid derivatives, 58,59 phosphodiesterase inhibitors, 85 and Rho-kinase inhibitors. 38,62,73,81 Preclinical Motor Neuron Replacement Data.…”

Section: Cell Transplant-based Neurorestorationmentioning

confidence: 99%

Shifting the balance: cell-based therapeutics as modifiers of the amyotrophic lateral sclerosis–specific neuronal microenvironment

Riley

Sweeney

Boulis

2008

FOC

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✓ Recent advances in the laboratory have improved the current understanding of neurobiological mechanisms underlying the initiating events and pathological progression observed in amyotrophic lateral sclerosis (ALS). Whereas initial studies have revealed the late-stage intracellular cascades contributing to neuronal dysfunction and cell death, more recently collected data have begun to elucidate the presence and importance of a “non–cell autonomous” component indicating that affected glial cell subtypes may serve distinct and required roles. Pharmacological interventions for ALS have largely been disappointing likely in part because they have failed to address either the proximate events contributing to neuronal dysfunction and death or the deleterious contributions of non-neuronal cells within the local microenvironment. Alternatively, cell-based therapeutics offer the potential of a multifaceted approach oriented toward the dual ends of protecting remaining viable neurons and attempting to restore neuronal function lost as a manifestation of disease progression. The authors review the evolving knowledge of disease initiation and progression, with specific emphasis on the role of affected glia as crucial contributors to the observed ALS phenotype. This basis is used to underscore the potential roles of cell-based therapeutics as modifiers of the ALS-specific microenvironment.

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Docosahexaenoic acid and arachidonic acid are fundamental supplements for the induction of neuronal differentiation

Cited by 57 publications

References 15 publications

Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid

Improved spatial learning performance of fat-1 mice is associated with enhanced neurogenesis and neuritogenesis by docosahexaenoic acid

A key role for the peroxisomalABCD2transporter in fatty acid homeostasis

Shifting the balance: cell-based therapeutics as modifiers of the amyotrophic lateral sclerosis–specific neuronal microenvironment

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