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Sea urchin embryonic development provides a model for evaluating therapies against beta-amyloid toxicity.

Publication ,  Journal Article
Buznikov, GA; Nikitina, LA; Bezuglov, VV; Milosević, I; Lazarević, L; Rogac, L; Ruzdijić, S; Slotkin, TA; Rakić, LM
Published in: Brain Res Bull
January 31, 2008

Accumulation of beta-amyloid protein is an Alzheimer's disease hallmark but also may be mechanistically involved in neurodegeneration. One of its cleavage peptides, Abeta42, has been used to evaluate the mechanisms underlying amyloid-induced cytotoxicity and targeting of acetylcholine systems. We studied Sphaerechinus granularis sea urchin embryos which utilize acetylcholine and other neurotransmitters as morphogens. At a threshold concentration of 0.1 microM Abeta42, there was damage to the larval skeleton, accumulation of ectodermal cells in the blastocoele and underdevelopment of larval arms. Raising the Abeta42 concentration to 0.2-0.4 microM produced anomalies depending on the stage at which Abeta42 was introduced: at the first cleavage divisions, abnormalities appeared within 1-2 cell cycles; at the mid-blastula stage, the peak period of sensitivity to Abeta42, gastrulation was blocked; at later stages, there was progressive damage to the larval skeleton, digestive tract and larval spicules, as well as regression of larval arms. Each of these anomalies could be offset by the addition of lipid-permeable analogs of acetylcholine (arachidonoyl dimethylaminoethanol), serotonin (arachidonoyl serotonin) and cannabinoids (arachidonoyl vanillylamine), with the greatest activity exhibited by the acetylcholine analog. These results indicate that sea urchin embryos provide a model suitable to characterize the mechanisms underlying the cytotoxicity of Abeta42, as well as providing a system that enables the rapid screening of potential therapeutic interventions. The protection provided by neurotransmitter analogs, especially that for acetylcholine, points to unsuspected advantages of existing therapies that enhance cholinergic function, as well as indicating novel approaches that may prove protective in Alzheimer's disease.

Duke Scholars

Published In

Brain Res Bull

DOI

ISSN

0361-9230

Publication Date

January 31, 2008

Volume

75

Issue

1

Start / End Page

94 / 100

Location

United States

Related Subject Headings

  • Sea Urchins
  • Peptide Fragments
  • Neurotransmitter Agents
  • Neurotoxicity Syndromes
  • Neurology & Neurosurgery
  • Embryonic Development
  • Embryo, Nonmammalian
  • Drug Evaluation
  • Dose-Response Relationship, Drug
  • Disease Models, Animal
 

Citation

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ICMJE
MLA
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Buznikov, G. A., Nikitina, L. A., Bezuglov, V. V., Milosević, I., Lazarević, L., Rogac, L., … Rakić, L. M. (2008). Sea urchin embryonic development provides a model for evaluating therapies against beta-amyloid toxicity. Brain Res Bull, 75(1), 94–100. https://doi.org/10.1016/j.brainresbull.2007.07.026
Buznikov, Gennady A., Lyudmila A. Nikitina, Vladimir V. Bezuglov, Ivan Milosević, Lidija Lazarević, Ljubica Rogac, Sabera Ruzdijić, Theodore A. Slotkin, and Ljubisa M. Rakić. “Sea urchin embryonic development provides a model for evaluating therapies against beta-amyloid toxicity.Brain Res Bull 75, no. 1 (January 31, 2008): 94–100. https://doi.org/10.1016/j.brainresbull.2007.07.026.
Buznikov GA, Nikitina LA, Bezuglov VV, Milosević I, Lazarević L, Rogac L, et al. Sea urchin embryonic development provides a model for evaluating therapies against beta-amyloid toxicity. Brain Res Bull. 2008 Jan 31;75(1):94–100.
Buznikov, Gennady A., et al. “Sea urchin embryonic development provides a model for evaluating therapies against beta-amyloid toxicity.Brain Res Bull, vol. 75, no. 1, Jan. 2008, pp. 94–100. Pubmed, doi:10.1016/j.brainresbull.2007.07.026.
Buznikov GA, Nikitina LA, Bezuglov VV, Milosević I, Lazarević L, Rogac L, Ruzdijić S, Slotkin TA, Rakić LM. Sea urchin embryonic development provides a model for evaluating therapies against beta-amyloid toxicity. Brain Res Bull. 2008 Jan 31;75(1):94–100.
Journal cover image

Published In

Brain Res Bull

DOI

ISSN

0361-9230

Publication Date

January 31, 2008

Volume

75

Issue

1

Start / End Page

94 / 100

Location

United States

Related Subject Headings

  • Sea Urchins
  • Peptide Fragments
  • Neurotransmitter Agents
  • Neurotoxicity Syndromes
  • Neurology & Neurosurgery
  • Embryonic Development
  • Embryo, Nonmammalian
  • Drug Evaluation
  • Dose-Response Relationship, Drug
  • Disease Models, Animal