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Cannabidiol Reverses Deficits in Hippocampal LTP in a Model of Alzheimer’s Disease

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Abstract

Here we demonstrate for the first time that cannabidiol (CBD) acts to protect synaptic plasticity in an in vitro model of Alzheimer’s disease (AD). The non-psycho active component of Cannabis sativa, CBD has previously been shown to protect against the neurotoxic effects of beta amyloid peptide (Aβ) in cell culture and cognitive behavioural models of neurodegeneration. Hippocampal long-term potentiation (LTP) is an activity dependent increase in synaptic efficacy often used to study cellular mechanisms related to memory. Here we show that acute application of soluble oligomeric beta amyloid peptide (Aβ1–42) associated with AD, attenuates LTP in the CA1 region of hippocampal slices from C57Bl/6 mice. Application of CBD alone did not alter LTP, however pre-treatment of slices with CBD rescued the Aβ1–42 mediated deficit in LTP. We found that the neuroprotective effects of CBD were not reversed by WAY100635, ZM241385 or AM251, demonstrating a lack of involvement of 5HT1A, adenosine (A2A) or Cannabinoid type 1 (CB1) receptors respectively. However in the presence of the PPARγ antagonist GW9662 the neuroprotective effect of CBD was prevented. Our data suggests that this major component of Cannabis sativa, which lacks psychoactivity may have therapeutic potential for the treatment of AD.

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Authors and Affiliations

  1. School of Biomolecular and Biomedical Sciences, Conway Institute, University College Dublin, Dublin 4, Ireland

    Blathnaid Hughes & Caroline E. Herron

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  1. Blathnaid Hughes
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  2. Caroline E. Herron
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Correspondence to Caroline E. Herron.

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Hughes, B., Herron, C.E. Cannabidiol Reverses Deficits in Hippocampal LTP in a Model of Alzheimer’s Disease. Neurochem Res 44, 703–713 (2019). https://doi.org/10.1007/s11064-018-2513-z

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  • DOI: https://doi.org/10.1007/s11064-018-2513-z

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