Sea Urchin Embryos and Larvae as Biosensors for Neurotoxicants

Buznikov, G. A.; Slotkin, Theodore A.; Lauder, Jean M.

doi:10.1002/0471140856.tx0106s16

Cited by 16 publications

(35 citation statements)

References 15 publications

(37 reference statements)

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“…These concentration ranges are similar to those shown to be required for Aβ42 toxicity in other lower organisms [20,22,30,33,51]. Lipophilic analogs of ACh (arachidonoyl dimethylaminoethanol, AA-DMAE), 5HT (arachidonoyl 5HT, AA-5-HT), and cannabinoids-vanilloids (arachidonoyl vanillylamine, AA-VAN) were evaluated at 10-40 µM, a concentration range found to be optimal in our previous experiments with a variety of neurotoxicants [12,15,19], including Aβ42 [13]. These substances were synthesized in the laboratory of Dr. V.V.…”

Section: Methodsmentioning

confidence: 57%

Section: Methodsmentioning

confidence: 99%

“…The optimal conditions for maintaining the adults and embryos have been described in detail previously [9,14,16,19]. In brief, gametes were harvested and the eggs were fertilized and incubated using standard techniques [12,16,19]. Eggs or sperm were obtained by injecting the animals with 1 ml of 0.55 M KCl, and embryos and larvae were cultured at 21°C in artificial seawater (ASW; 445 mM NaCl, 24.6 mM MgCl 2 , 18.1 mM MgSO 4 , 9.2 mM KCl, 2.36 mM NaHCO 3 , 11.5 mM CaCl 2 ; pH 7.4), maintaining complete O 2 saturation.…”

Section: Methodsmentioning

confidence: 99%

“…The sea urchin embryo, develops the ability to synthesize, store and release ACh and other neurotransmitters, and possesses the analogous receptors and downstream signaling cascades, all of which appear rapidly over a defined developmental period and act as morphogens that control cell differentiation and assembly of the embryo and larva [10,13,20,26]. Agents that target specific neurotrophic mechanisms or signaling cascades in the mammalian brain, produce structural anomalies during sea urchin morphogenesis that are readily characterized with routine light microscopy [4,5,[9][10][11][12][17][18][19]36,41]. Further, normal sea urchin development is well characterized at both structural and biochemical levels; consequently, the mechanisms of action and consequences of exposure for a wide variety of embryotoxins, teratogens and neurotoxicants have been evaluated with this system [5,9,11,12,16,19,27,36].…”

Section: Introductionmentioning

confidence: 99%

“…Agents that target specific neurotrophic mechanisms or signaling cascades in the mammalian brain, produce structural anomalies during sea urchin morphogenesis that are readily characterized with routine light microscopy [4,5,[9][10][11][12][17][18][19]36,41]. Further, normal sea urchin development is well characterized at both structural and biochemical levels; consequently, the mechanisms of action and consequences of exposure for a wide variety of embryotoxins, teratogens and neurotoxicants have been evaluated with this system [5,9,11,12,16,19,27,36]. Unlike mammalian models, each sea urchin produces thousands to millions of offspring that develop rapidly and simultaneously, with a coordinated and highly specific sequence of morphological events, so that toxicant exposures produce uniform phenotypes for any given critical exposure period [11,12,19,36].…”

Section: Introductionmentioning

confidence: 99%

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

Buznikov

Nikitina

Seidler

et al. 2008

Neurotoxicology and Teratology

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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 Correspondence: Dr. T.A. Slotkin, Dept. of Pharmacology & Cancer Biology, Box 3813 DUMC, Duke University Medical Center, Durham, NC 27710-3813, Tel (919) 681 8015, Fax (919) 684 8197, e-mail: t.slotkin@duke.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. 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 β-amyloid 1-42 (Aβ42), the neurotoxic APP fragment contained within neurodegenerative plaques in Alzheimer's Disease. Although both peptides elicited dysmorphogenesis, Aβ42 was far more potent; in addition, whereas Aβ42 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 α-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, α-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. NIH Public Access

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