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Amyloid precursor protein 96-110 and beta-amyloid 1-42 elicit developmental anomalies in sea urchin embryos and larvae that are alleviated by neurotransmitter analogs for acetylcholine, serotonin and cannabinoids.

Publication ,  Journal Article
Buznikov, GA; Nikitina, LA; Seidler, FJ; Slotkin, TA; Bezuglov, VV; Milosević, I; Lazarević, L; Rogac, L; Ruzdijić, S; Rakić, LM
Published in: Neurotoxicol Teratol
2008

Amyloid precursor protein (APP) is overexpressed in the developing brain and portions of its extracellular domain, especially amino acid residues 96-110, play an important role in neurite outgrowth and neural cell differentiation. In the current study, we evaluated the developmental abnormalities caused by administration of exogenous APP(96-110) in sea urchin embryos and larvae, which, like the developing mammalian brain, utilize acetylcholine and other neurotransmitters as morphogens; effects were compared to those of beta-amyloid 1-42 (Abeta42), the neurotoxic APP fragment contained within neurodegenerative plaques in Alzheimer's Disease. Although both peptides elicited dysmorphogenesis, Abeta42 was far more potent; in addition, whereas Abeta42 produced abnormalities at developmental stages ranging from early cleavage divisions to the late pluteus, APP(96-110) effects were restricted to the intermediate, mid-blastula stage. For both agents, anomalies were prevented or reduced by addition of lipid-permeable analogs of acetylcholine, serotonin or cannabinoids; physostigmine, a carbamate-derived cholinesterase inhibitor, was also effective. In contrast, agents that act on NMDA receptors (memantine) or alpha-adrenergic receptors (nicergoline), and that are therapeutic in Alzheimer's Disease, were themselves embryotoxic, as was tacrine, a cholinesterase inhibitor from a different chemical class than physostigmine. Protection was also provided by agents acting downstream from receptor-mediated events: increasing cyclic AMP with caffeine or isobutylmethylxanthine, or administering the antioxidant, a-tocopherol, were all partially effective. Our findings reinforce a role for APP in development and point to specific interactions with neurotransmitter systems that act as morphogens in developing sea urchins as well as in the mammalian brain.

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Published In

Neurotoxicol Teratol

DOI

ISSN

0892-0362

Publication Date

2008

Volume

30

Issue

6

Start / End Page

503 / 509

Location

United States

Related Subject Headings

  • Toxicology
  • Time Factors
  • Serotonin
  • Sea Urchins
  • Peptide Fragments
  • Larva
  • Embryonic Development
  • Embryo, Nonmammalian
  • Drug Interactions
  • Dose-Response Relationship, Drug
 

Citation

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Buznikov, G. A., Nikitina, L. A., Seidler, F. J., Slotkin, T. A., Bezuglov, V. V., Milosević, I., … Rakić, L. M. (2008). Amyloid precursor protein 96-110 and beta-amyloid 1-42 elicit developmental anomalies in sea urchin embryos and larvae that are alleviated by neurotransmitter analogs for acetylcholine, serotonin and cannabinoids. Neurotoxicol Teratol, 30(6), 503–509. https://doi.org/10.1016/j.ntt.2008.05.003
Buznikov, Gennady A., Lyudmila A. Nikitina, Frederic J. Seidler, Theodore A. Slotkin, Vladimir V. Bezuglov, Ivan Milosević, Lidija Lazarević, Ljubica Rogac, Sabera Ruzdijić, and Ljubisa M. Rakić. “Amyloid precursor protein 96-110 and beta-amyloid 1-42 elicit developmental anomalies in sea urchin embryos and larvae that are alleviated by neurotransmitter analogs for acetylcholine, serotonin and cannabinoids.Neurotoxicol Teratol 30, no. 6 (2008): 503–9. https://doi.org/10.1016/j.ntt.2008.05.003.
Buznikov GA, Nikitina LA, Seidler FJ, Slotkin TA, Bezuglov VV, Milosević I, Lazarević L, Rogac L, Ruzdijić S, Rakić LM. Amyloid precursor protein 96-110 and beta-amyloid 1-42 elicit developmental anomalies in sea urchin embryos and larvae that are alleviated by neurotransmitter analogs for acetylcholine, serotonin and cannabinoids. Neurotoxicol Teratol. 2008;30(6):503–509.
Journal cover image

Published In

Neurotoxicol Teratol

DOI

ISSN

0892-0362

Publication Date

2008

Volume

30

Issue

6

Start / End Page

503 / 509

Location

United States

Related Subject Headings

  • Toxicology
  • Time Factors
  • Serotonin
  • Sea Urchins
  • Peptide Fragments
  • Larva
  • Embryonic Development
  • Embryo, Nonmammalian
  • Drug Interactions
  • Dose-Response Relationship, Drug