Behavioral phenotyping of a transgenic Caenorhabditis elegans expressing neuronal amyloid-beta.
Alzheimer's disease (AD) is rapidly reaching epidemic proportions in the United States, currently affecting more than 5 million individuals and predicted to affect 14 million by 2050. Despite a general consensus that the amyloid-beta (Abeta) protein plays a significant role in disease progression, the underlying pathology of the disease is not entirely clear. Caenorhabditis elegans is a simple organism that has been used as a model for basic mechanistic studies on the underlying pathological processes involved in AD. Previous studies from our labs demonstrated that transgenic C. elegans with muscle specific expression of human Abeta undergo rapid paralysis, and worms with neuronal expression of Abeta show deficits in chemotaxis to volatile chemicals. In this study, we evaluate the effect of neuron specific expression of Abeta on multiple neuronally controlled behaviors in a transgenic C. elegans. These worms demonstrate deficits in odorant preference associative learning behavior, and the serotonin-controlled behaviors experience-dependent learning and egg laying. These newly identified learning-deficit behavioral phenotypes in the neuronal Abeta C. elegans suggest that the model may be used to elucidate underlying pathological events related to development of AD and for pharmaceutical intervention.
Dosanjh
Laura E
LE
Department of Pharmaceutical Sciences, School of Pharmacy, University of Maryland, Baltimore, MD 21201, USA.
Brown
Marishka K
MK
Rao
Gautam
G
Link
Christopher D
CD
Luo
Yuan
Y
D000544:Alzheimer Disease / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D017173:Caenorhabditis elegans; D002492:Central Nervous System Depressants / Q000494:pharmacology; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D000431:Ethanol / Q000494:pharmacology; D006801:Humans; D007859:Learning Disabilities / Q000235:genetics; D008136:Longevity / Q000235:genetics; D009043:Motor Activity / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009812:Odorants; D010641:Phenotype; D012098:Reproduction / Q000235:genetics; D012701:Serotonin / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D002492:Central Nervous System Depressants; D012701:Serotonin; D000431:Ethanol