Core--Neurobehavioral Assessment

描述（由申请人提供）：该核心的总体目标是进行旨在 定义慢性低水平农药暴露对小鼠神经行为发育的影响。行为毒理学核心将为两个研究项目提供服务，一个涉及产前接触农药，另一个涉及产后早期接触农药。通过使用发育神经毒性试验组合，核心将提供评价中枢神经系统功能发育的能力。该测试组合包括测量小鼠的运动协调、反射反应、伤害感受、学习和记忆以及发育标志的出现。将根据当前支持期内PON 1-/-和PON 1 +/+小鼠获得的结果确定用于遗传易感性研究的确切试验。例如，在Morris水迷宫和旷场试验中，治疗组之间存在显著差异（见PON 1多态性研究进展报告）。因此，目前研究确定的不受OP暴露影响的测试（例如，例如，在一个实施例中，可能是旋转杆和径向臂迷宫测试）可以被其他行为测试所取代，例如平台反转或延迟匹配到 Morris水迷宫的样本变体或检查对新物体的反应的旷场测试的变体。决定哪些测试包括在电池将取决于目前正在进行神经行为评估的小鼠获得的结果。 神经行为评估机构是一个无特定病原体（SPF）实验室，位于健康科学大楼五楼，靠近中心动物机构和几个中心研究者实验室。该设施由三个房间（273平方英尺，78平方英尺和53平方英尺）组成，空间可容纳多达25个SPF小鼠笼。比较医学系的中心设施位于行为毒理学设施的楼上，是AAALAC认证的SPF设施，有足够的空间容纳小鼠。 神经行为评估设施最初是在本资助期内建立的，以解决该中心的具体目标。到2001年上半年，异常高的新生儿死亡率一直阻碍着殖民地的扩张，使其无法达到足以开始行为测试的规模。通过将小鼠饲养室和行为测试实验室从校外大楼搬到健康科学大楼，并在这些房间实施SPF程序，克服了这一困难。这一策略消除了研究人员在校外设施中一直在努力解决的高新生儿死亡率问题，并具有将神经行为毒理学设施放置在健康科学大楼其他中心实验室附近的额外优势。该设施于2002年1月2日由UW IACUC和兽医服务部门检查并批准。批准后立即开始行为研究。

Description (provided by applicant): The overall goal of this core is to conduct studies aimed at defining the effects of chronic low-level pesticide exposure on neurobehavioral development in mice. The Behavioral Toxicology Core will provide services for two research projects, one involving pre-natal exposure to pesticides, and the other early postnatal exposure. The Core will provide the capability of evaluating the functional development of the central nervous system, through the use of a Developmental Neurotoxicity Test Battery. This test battery includes measures of motor coordination, reflex responses, nociception, learning and memory, and the appearance of developmental landmarks in mice. The exact tests to be used for the Genetic Susceptibility study will be determined by the results obtained with the PON1-/- and PON1+/+ mice in the current period of support. For example, there were significant differences among treatment groups in the Morris water maze and open field tests (see progress report for the PON1 Polymorphisms study). Thus, tests which are determined by the current studies not to be affected by OP exposure (e. g., possibly the rotarod and radial arm maze tests) might be replaced by other behavioral tests, such as the platform reversal or delayed-matching-to- sample variants of the Morris water maze or a variant of the open field test that examines response to a novel object. The decision of which tests to include in the battery will hinge on the results obtained with the mice currently under neurobehavioral assessment. The Neurobehavioral Assessment Facility is a specific pathogen free (SPF) laboratory located on the fifth floor of the Health Sciences Building, close to the central animal facility and to several of the Center investigator laboratories. The facility is comprised of three rooms (273 sq ft, 78 sq ft and 53 sq ft), with space for housing up to 25 cages of SPF mice. The Department of Comparative Medicine's central facility, located just upstairs from the Behavioral Toxicology Facility, is an AAALAC-accredited SPF facility that has ample space for mouse housing. The Neurobehavioral Assessment Facility was first established in the current funding period to address the specific aims of the Center. Into the early part of 2001, an abnormally high neonatal mortality rate had been preventing expansion of the colony to a size large enough to begin behavioral testing. This difficulty was overcome by moving the mouse housing rooms and behavioral testing laboratory from an off-campus building to the Health Sciences Building, and by implementing SPF procedures in these rooms. This strategy has eliminated the high neonatal mortality that the investigators had been struggling with at the off-campus facility, and has the added advantage of placing the Neurobehavioral Toxicology Facility near the other Center laboratories in the Health Sciences Building. The facility was inspected and approved by the UW IACUC and veterinary services on January 2,2002. Behavioral studies commenced immediately after approval.