Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Echinobase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
Echinobase
ECB-ART-40746
Neurotoxicol Teratol 2008 Jan 01;306:503-9. doi: 10.1016/j.ntt.2008.05.003.
Show Gene links Show Anatomy links

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.

Buznikov GA , Nikitina LA , Seidler FJ , Slotkin TA , Bezuglov VV , Milosević I , Lazarević L , Rogac L , Ruzdijić S , Rakić LM .


???displayArticle.abstract???
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.

???displayArticle.pubmedLink??? 18565728
???displayArticle.pmcLink??? PMC2579926
???displayArticle.link??? Neurotoxicol Teratol
???displayArticle.grants??? [+]

Genes referenced: aplp1 LOC100887844 LOC100888622 LOC115919856 LOC115919910 LOC590297

References [+] :
Bezuglov, [Artificially functionalized polyenoic fatty acids--a new lipid bioregulators]. 1997, Pubmed, Echinobase