Fatty acids & Synapse Research News

Docosahexaenoic acid and synaptic protection in Alzheimer's disease mice.

Oster T, Pillot T

Docosahexaenoic acid and synaptic protection in Alzheimer's disease mice.

Biochim Biophys Acta. 2010 Aug;1801(8):791-8

Authors: Oster T, Pillot T

Alzheimer's disease (AD) is a major public health concern due to longer life expectancy in the Western countries. Amyloid-beta (Abeta) oligomers are considered the proximate effectors in the early stages of AD. AD-related cognitive impairment, synaptic loss and neurodegeneration result from interactions of Abeta oligomers with the synaptic membrane and subsequent activation of pro-apoptotic signalling pathways. Therefore, membrane structure and lipid status appear determinant in Abeta-induced toxicity. Numerous epidemiological studies have highlighted the beneficial influence of docosahexaenoic acid (DHA, C22:6 n-3) on the preservation of synaptic function and memory capacities in aged individuals or upon Abeta exposure, whereas its deficiency is presented as a risk factor for AD. An elevated number of studies have been reporting the beneficial effects of dietary DHA supplementation on cognition and synaptic integrity in various AD models. In this review, we describe the important potential of DHA to preserve neuronal and brain functions and classified its numerous molecular and cellular effects from impact on membrane lipid content and organisation to activation of signalling pathways sustaining synaptic function and neuronal survival. DHA appears as one of the most valuable diet ingredients whose neuroprotective properties could be crucial for designing nutrition-based strategies able to prevent AD as well as other lipid- and age-related diseases whose prevalence is progressing in elderly populations.

PMID: 20211757 [PubMed - indexed for MEDLINE]

Basement membrane protein nidogen-1 shapes hippocampal synaptic plasticity and excitability.

Basement membrane protein nidogen-1 shapes hippocampal synaptic plasticity and excitability.

Hippocampus. 2010 May;20(5):608-20

Authors: Vasudevan A, Ho MS, WeiergrÃ¤ber M, Nischt R, Schneider T, Lie A, Smyth N, KÃ¶hling R

The basement membrane (BM) is a specialized form of extracellular matrix (ECM) underlying epithelia and endothelia and surrounding many types of mesenchymal cells. Nidogen, along with collagen IV and laminin, is a major component of BMs. Although certain ECM proteins such as laminin or reelin influence neuronal function via interactions with cell-surface receptors such as integrins, behavioral neurological impairments due to deficits of BM components have been recognized only recently. Here, alterations in neuronal network function underlying these behavioral changes are revealed. Using nidogen-1 knockout mice, with or without additional heterozygous nidogen-2 knockout (NID1(-/-)/NID2(+/+) or NID1(-/-)/NID2(+/-)), we demonstrate that nidogen is essential for normal neuronal network excitability and plasticity. In nidogen-1 knockouts, seizurelike behavior occurs, and epileptiform spiking was seen in hippocampal in vivo EEG recordings. In vitro, hippocampal field potential recordings revealed that lack of nidogen-1, while not causing conspicuous morphological changes, led to the appearance of spontaneous and evoked epileptiform activity, significant increase of the input/output ratio of synaptically evoked responses in CA1 and dentate gyrus, as well as of paired pulse accentuation, and loss of perforant-path long-term synaptic potentiation. Nidogen-1 is thus essential for normal network excitability and plasticity.

PMID: 19530222 [PubMed - indexed for MEDLINE]