The overall objective of the proposed research is to elucidate the molecular mechanisms by which short-term exposure to harmful algal bloom (HAB) toxins and marine toxicants during development causes physiological and neurological abnormalities later in life. It is now well known that the early life environment can have a profound effect on the health of adults (the developmental origins of health and disease). However, the mechanisms by which developmental exposure elicits effects later in life are not understood. The central hypothesis of this research is that embryonic exposure to certain marine toxins or toxicants alters epigenetic programming, leading to long-term effects on gene expression in adult tissues and ultimately contributing to altered neurobehavioral function in adults. We will conduct studies to identify a core set of genes that show long-term transcriptional changes due to changes in the early life chemical environment and identify their epigenetic signature to determine the mechanistic link between adult phenotype and early life exposures. These studies will be conducted using zebrafish, a powerful model organism for research on developmental mechanisms.
In Aim 1, we will test the hypothesis that developmental exposure to HAB toxins (saxitoxin, domoic acid) and toxicants (PCB126, PCB153) causes later life changes in gene expression and behavior.
In Aim 2, we will test the hypothesis that adult effects resulting from developmental exposure to HAB toxins and toxicants are caused by epigenetic reprogramming of gene expression, focusing on altered DNA methylation and microRNA expression.
In Aim 3, we will determine whether the proximal mechanisms involving receptors and ion channels known to be responsible for the acute effects of these chemicals are also involved in the delayed effects seen in adults exposed to chemicals during development. This research will identify molecular bases for adult effects occurring after developmental exposure to important HAB toxins and marine toxicants, and determine whether there are similar or convergent epigenetic mechanisms involved.

Public Health Relevance

Project 3 addresses an important public health problem: effects of early life (embryonic / perinatal) exposure to marine chemicals on neurological development and later-life function. The proposed studies will provide an understanding of the long-term health consequences of developmental exposure to marine toxins and toxicants, critical in assessing public health risks associated with widespread exposure to these chemicals.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Program Projects (P01)
Project #
1P01ES021923-01
Application #
8413153
Study Section
Special Emphasis Panel (ZES1-LKB-J (P1))
Project Start
Project End
Budget Start
2012-09-24
Budget End
2013-07-31
Support Year
1
Fiscal Year
2012
Total Cost
$125,299
Indirect Cost
$44,348
Name
Woods Hole Oceanographic Institution
Department
Type
DUNS #
001766682
City
Woods Hole
State
MA
Country
United States
Zip Code
02543
Aluru, Neelakanteswar; Karchner, Sibel I; Glazer, Lilah (2017) Early Life Exposure to Low Levels of AHR Agonist PCB126 (3,3',4,4',5-Pentachlorobiphenyl) Reprograms Gene Expression in Adult Brain. Toxicol Sci 160:386-397
Brosnahan, Michael L; Ralston, David K; Fischer, Alexis D et al. (2017) Bloom termination of the toxic dinoflagellate Alexandrium catenella: Vertical migration behavior, sediment infiltration, and benthic cyst yield. Limnol Oceanogr 62:2829-2849
Ganju, Neil K; Brush, Mark J; Rashleigh, Brenda et al. (2016) Progress and challenges in coupled hydrodynamic-ecological estuarine modeling. Estuaries Coast 39:311-332
Glazer, Lilah; Hahn, Mark E; Aluru, Neelakanteswar (2016) Delayed effects of developmental exposure to low levels of the aryl hydrocarbon receptor agonist 3,3',4,4',5-pentachlorobiphenyl (PCB126) on adult zebrafish behavior. Neurotoxicology 52:134-43
Zhou, Jin; Lyu, Yihua; Richlen, Mindy et al. (2016) Quorum sensing is a language of chemical signals and plays an ecological role in algal-bacterial interactions. CRC Crit Rev Plant Sci 35:81-105
Sehein, Taylor; Richlen, Mindy L; Nagai, Satoshi et al. (2016) CHARACTERIZATION OF 17 NEW MICROSATELLITE MARKERS FOR THE DINOFLAGELLATE ALEXANDRIUM FUNDYENSE (DINOPHYCEAE), A HARMFUL ALGAL BLOOM SPECIES. J Appl Phycol 28:1677-1681
Lemaire, Benjamin; Kubota, Akira; O'Meara, Conor M et al. (2016) Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders. Toxicol Appl Pharmacol 296:73-84
Han, Myungsoo; Lee, Haeok; Anderson, Donald M et al. (2016) Paralytic shellfish toxin production by the dinoflagellate Alexandrium pacificum (Chinhae Bay, Korea) in axenic, nutrient-limited chemostat cultures and nutrient-enriched batch cultures. Mar Pollut Bull 104:34-43
Richlen, Mindy L; Zielinski, Oliver; Holinde, Lars et al. (2016) Distribution of Alexandrium fundyense (Dinophyceae) cysts in Greenland and Iceland, with an emphasis on viability and growth in the Arctic. Mar Ecol Prog Ser 547:33-46
Roncalli, Vittoria; Turner, Jefferson T; Kulis, David et al. (2016) The effect of the toxic dinoflagellate Alexandrium fundyense on the fitness of the calanoid copepod Calanus finmarchicus. Harmful Algae 51:56-66

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