Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function

Dehua Cao, Karl Kevala, Jeffrey Kim, Hyun-Seuk Moon, Sang Beom Jun, David Lovinger, Hee Yong Kim

Research output: Contribution to journalArticle

198 Citations (Scopus)

Abstract

Docosahexaenoic acid (DHA, 22:6n-3), the major polyunsaturated fatty acid accumulated in the brain during development, has been implicated in learning and memory, but underlying cellular mechanisms are not clearly understood. Here, we demonstrate that DHA significantly affects hippocampal neuronal development and synaptic function in developing hippocampi. In embryonic neuronal cultures, DHA supplementation uniquely promoted neurite growth, synapsin puncta formation and synaptic protein expression, particularly synapsins and glutamate receptors. In DHA-supplemented neurons, spontaneous synaptic activity was significantly increased, mostly because of enhanced glutamatergic synaptic activity. Conversely, hippocampal neurons from DHA-depleted fetuses showed inhibited neurite growth and synaptogenesis. Furthermore, n-3 fatty acid deprivation during development resulted in marked decreases of synapsins and glutamate receptor subunits in the hippocampi of 18-day-old pups with concomitant impairment of long-term potentiation, a cellular mechanism underlying learning and memory. While levels of synapsins and NMDA receptor subunit NR2A were decreased in most hippocampal regions, NR2A expression was particularly reduced in CA3, suggesting possible role of DHA in CA3-NMDA receptor-dependent learning and memory processes. The DHA-induced neurite growth, synaptogenesis, synapsin, and glutamate receptor expression, and glutamatergic synaptic function may represent important cellular aspects supporting the hippocampus-related cognitive function improved by DHA.

Original languageEnglish
Pages (from-to)510-521
Number of pages12
JournalJournal of Neurochemistry
Volume111
Issue number2
DOIs
Publication statusPublished - 2009 Oct 1
Externally publishedYes

Fingerprint

Synapsins
Docosahexaenoic Acids
Glutamate Receptors
Neurites
Hippocampus
Learning
N-Methyl-D-Aspartate Receptors
Data storage equipment
Neurons
Growth
Long-Term Potentiation
Omega-3 Fatty Acids
Unsaturated Fatty Acids
Cognition
Brain
Fetus
Proteins

Keywords

  • Docosahexaenoic acid
  • Hippocampal development
  • Long-term potentiation
  • Neurite growth
  • Synaptic function
  • Synaptogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. / Cao, Dehua; Kevala, Karl; Kim, Jeffrey; Moon, Hyun-Seuk; Jun, Sang Beom; Lovinger, David; Kim, Hee Yong.

In: Journal of Neurochemistry, Vol. 111, No. 2, 01.10.2009, p. 510-521.

Research output: Contribution to journalArticle

Cao, Dehua ; Kevala, Karl ; Kim, Jeffrey ; Moon, Hyun-Seuk ; Jun, Sang Beom ; Lovinger, David ; Kim, Hee Yong. / Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function. In: Journal of Neurochemistry. 2009 ; Vol. 111, No. 2. pp. 510-521.
@article{bb124b22f5aa4fbdaf7d153c023cffca,
title = "Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function",
abstract = "Docosahexaenoic acid (DHA, 22:6n-3), the major polyunsaturated fatty acid accumulated in the brain during development, has been implicated in learning and memory, but underlying cellular mechanisms are not clearly understood. Here, we demonstrate that DHA significantly affects hippocampal neuronal development and synaptic function in developing hippocampi. In embryonic neuronal cultures, DHA supplementation uniquely promoted neurite growth, synapsin puncta formation and synaptic protein expression, particularly synapsins and glutamate receptors. In DHA-supplemented neurons, spontaneous synaptic activity was significantly increased, mostly because of enhanced glutamatergic synaptic activity. Conversely, hippocampal neurons from DHA-depleted fetuses showed inhibited neurite growth and synaptogenesis. Furthermore, n-3 fatty acid deprivation during development resulted in marked decreases of synapsins and glutamate receptor subunits in the hippocampi of 18-day-old pups with concomitant impairment of long-term potentiation, a cellular mechanism underlying learning and memory. While levels of synapsins and NMDA receptor subunit NR2A were decreased in most hippocampal regions, NR2A expression was particularly reduced in CA3, suggesting possible role of DHA in CA3-NMDA receptor-dependent learning and memory processes. The DHA-induced neurite growth, synaptogenesis, synapsin, and glutamate receptor expression, and glutamatergic synaptic function may represent important cellular aspects supporting the hippocampus-related cognitive function improved by DHA.",
keywords = "Docosahexaenoic acid, Hippocampal development, Long-term potentiation, Neurite growth, Synaptic function, Synaptogenesis",
author = "Dehua Cao and Karl Kevala and Jeffrey Kim and Hyun-Seuk Moon and Jun, {Sang Beom} and David Lovinger and Kim, {Hee Yong}",
year = "2009",
month = "10",
day = "1",
doi = "10.1111/j.1471-4159.2009.06335.x",
language = "English",
volume = "111",
pages = "510--521",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Docosahexaenoic acid promotes hippocampal neuronal development and synaptic function

AU - Cao, Dehua

AU - Kevala, Karl

AU - Kim, Jeffrey

AU - Moon, Hyun-Seuk

AU - Jun, Sang Beom

AU - Lovinger, David

AU - Kim, Hee Yong

PY - 2009/10/1

Y1 - 2009/10/1

N2 - Docosahexaenoic acid (DHA, 22:6n-3), the major polyunsaturated fatty acid accumulated in the brain during development, has been implicated in learning and memory, but underlying cellular mechanisms are not clearly understood. Here, we demonstrate that DHA significantly affects hippocampal neuronal development and synaptic function in developing hippocampi. In embryonic neuronal cultures, DHA supplementation uniquely promoted neurite growth, synapsin puncta formation and synaptic protein expression, particularly synapsins and glutamate receptors. In DHA-supplemented neurons, spontaneous synaptic activity was significantly increased, mostly because of enhanced glutamatergic synaptic activity. Conversely, hippocampal neurons from DHA-depleted fetuses showed inhibited neurite growth and synaptogenesis. Furthermore, n-3 fatty acid deprivation during development resulted in marked decreases of synapsins and glutamate receptor subunits in the hippocampi of 18-day-old pups with concomitant impairment of long-term potentiation, a cellular mechanism underlying learning and memory. While levels of synapsins and NMDA receptor subunit NR2A were decreased in most hippocampal regions, NR2A expression was particularly reduced in CA3, suggesting possible role of DHA in CA3-NMDA receptor-dependent learning and memory processes. The DHA-induced neurite growth, synaptogenesis, synapsin, and glutamate receptor expression, and glutamatergic synaptic function may represent important cellular aspects supporting the hippocampus-related cognitive function improved by DHA.

AB - Docosahexaenoic acid (DHA, 22:6n-3), the major polyunsaturated fatty acid accumulated in the brain during development, has been implicated in learning and memory, but underlying cellular mechanisms are not clearly understood. Here, we demonstrate that DHA significantly affects hippocampal neuronal development and synaptic function in developing hippocampi. In embryonic neuronal cultures, DHA supplementation uniquely promoted neurite growth, synapsin puncta formation and synaptic protein expression, particularly synapsins and glutamate receptors. In DHA-supplemented neurons, spontaneous synaptic activity was significantly increased, mostly because of enhanced glutamatergic synaptic activity. Conversely, hippocampal neurons from DHA-depleted fetuses showed inhibited neurite growth and synaptogenesis. Furthermore, n-3 fatty acid deprivation during development resulted in marked decreases of synapsins and glutamate receptor subunits in the hippocampi of 18-day-old pups with concomitant impairment of long-term potentiation, a cellular mechanism underlying learning and memory. While levels of synapsins and NMDA receptor subunit NR2A were decreased in most hippocampal regions, NR2A expression was particularly reduced in CA3, suggesting possible role of DHA in CA3-NMDA receptor-dependent learning and memory processes. The DHA-induced neurite growth, synaptogenesis, synapsin, and glutamate receptor expression, and glutamatergic synaptic function may represent important cellular aspects supporting the hippocampus-related cognitive function improved by DHA.

KW - Docosahexaenoic acid

KW - Hippocampal development

KW - Long-term potentiation

KW - Neurite growth

KW - Synaptic function

KW - Synaptogenesis

UR - http://www.scopus.com/inward/record.url?scp=70349325995&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349325995&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2009.06335.x

DO - 10.1111/j.1471-4159.2009.06335.x

M3 - Article

C2 - 19682204

AN - SCOPUS:70349325995

VL - 111

SP - 510

EP - 521

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -