Date of Award

2013

Document Type

Honors Thesis (Open Access)

Department

Colby College. Biology Dept.

Advisor(s)

Melissa J. Glenn

Second Advisor

Andrea R. Tilden

Third Advisor

Catherine R. Bevier

Abstract

Choline is essential to the development and function of the central nervous system. Supplemental choline is neuroprotective against a variety of insults, including neurotoxins like dizocilpine (MK-801). MK-801 is an NMDA receptor antagonist that is frequently used in rodent models of psychological disorders. At low doses, it causes cognitive impairments, and at higher doses it induces motor deficits, anhedonia, and neuronal degeneration. The primary goals of the present study were to investigate whether prenatal choline supplementation protects against the cognitive impairments, motor deficits, and neuropathologies that are precipitated by MK-801 administration in adulthood. Adult male Sprague Dawley rats were fed either a standard or supplemented choline diet prenatally. Using the novelty preference test of object recognition, we examined three aspects of memory in relation to choline and MK-801: encoding, consolidation, and retrieval. Our first main finding was that choline protected memory consolidation; presently, we are not able to draw clear conclusions regarding memory encoding and retrieval, as control rats did not exhibit the expected patterns. We also observed that choline alleviated the motor response to MK-801, particularly ataxia. Using doublecortin to mark neurogenesis in the hippocampus and Fluoro-Jade B to mark degenerating axons in the anterior commissure, we found that this prenatal choline supplementation, in the face of MK-801 toxicity, protects against reduced hippocampal neurogenesis and may prevent neurodegeneration. Taken together, the current findings suggest that prenatal choline supplementation protects against a variety of behavioral and neural pathologies induced by the neurotoxin MK-801. This research contributes to the growing body of evidence supporting the robust neuroprotective capacity of choline.

Keywords

choline, dizocilpine, neurotoxins, memory

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