Buznikov_2008_Neurotoxicol.Teratol_30_503

Reference

Title : 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_2008_Neurotoxicol.Teratol_30_503
Author(s) : Buznikov GA , Nikitina LA , Seidler FJ , Slotkin TA , Bezuglov VV , Milosevic I , Lazarevic L , Rogac L , Ruzdijic S , Rakic LM
Ref : Neurotoxicology & Teratology , 30 :503 , 2008
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.

PubMedSearch : Buznikov_2008_Neurotoxicol.Teratol_30_503
PubMedID: 18565728

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Citations formats

Buznikov GA, Nikitina LA, Seidler FJ, Slotkin TA, Bezuglov VV, Milosevic I, Lazarevic L, Rogac L, Ruzdijic S, Rakic LM (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
Neurotoxicology & Teratology 30 :503

Buznikov GA, Nikitina LA, Seidler FJ, Slotkin TA, Bezuglov VV, Milosevic I, Lazarevic L, Rogac L, Ruzdijic S, Rakic LM (2008)
Neurotoxicology & Teratology 30 :503