Project Grant K01AA031531

TRANSLATIONAL RESEARCH TO ACCELERATE INTERVENTIONS FOR FETAL ALCOHOL SPECTRUM DISORDERS: EVALUATION OF PHYSICAL ACTIVITY AT BASIC AND CLINICAL LEVELS - PROJECT SUMMARY ALTHOUGH IDENTIFIED OVER 50 YEARS AGO, THERE ARE A LIMITED NUMBER OF INTERVENTIONS FOR FETAL ALCOHOL SPECTRUM DISORDERS (FASD), THE LEADING KNOWN PREVENTABLE NEURODEVELOPMENT DISORDERS IN THE U.S. NEUROPATHOLOGY ASSOCIATED WITH PRENATAL ALCOHOL EXPOSURE (PAE) ALTERS BEHAVIORAL, COGNITIVE, AND EMOTIONAL FUNCTIONS THAT PERSISTENT IN CHILDHOOD AND CAN PERSIST THROUGHOUT LIFE. BASIC SCIENCE ANIMAL MODELS HAVE BEEN INSTRUMENTAL IN UNDERSTANDING THE MECHANISMS OF ALCOHOL'S TERATOGENIC EFFECTS AS WELL AS ESSENTIAL TO INVESTIGATING POTENTIAL INTERVENTIONS. HOWEVER, DESPITE ROBUST PRECLINICAL EVIDENCE, THERE ARE A LIMITED NUMBER OF INTERVENTIONS IDENTIFIED IN BASIC SCIENCE MODELS BEING TRANSLATED TO CLINICAL USE. ONE SUCH INTERVENTION IS PHYSICAL ACTIVITY, WHICH MITIGATES ETHANOL-INDUCED BEHAVIORAL, COGNITIVE, AND MOLECULAR ALTERATIONS IN ANIMAL MODELS OF PAE. MOREOVER, PHYSICAL ACTIVITY HAS BEEN ASSOCIATED WITH IMPROVED COGNITIVE FUNCTION AND NEUROBEHAVIORAL MEASURES IN CHILDREN WITH OTHER, LESS PROMINENT NEURODEVELOPMENTAL DISORDERS. DESPITE THE LARGE BODY OF RESEARCH THAT SUPPORTS PHYSICAL ACTIVITY AS A POTENTIAL THERAPEUTIC FOR FASD, LIMITED CLINICAL STUDIES HAVE BEEN CONDUCTED IN THIS POPULATION. THEREFORE, THE PRIMARY AIM OF THIS K01 PROPOSAL IS TO PROVIDE TRANSLATIONAL RESEARCH TRAINING AND EXPERIENCE TO BRIDGE THE GAP BETWEEN BASIC AND CLINICAL SCIENCE AND ACCELERATE INTERVENTION RESEARCH FOR FASD. SPECIFICALLY, THE CANDIDATE WILL BEGIN TO CHARACTERIZE PHYSICAL ACTIVITY IN CHILDREN AND ADOLESCENTS WITH A HISTORY OF PAE AND WILL DETERMINE THE RELATIONSHIP BETWEEN PHYSICAL ACTIVITY, NEUROCOGNITION, AND MENTAL HEALTH. DATA FROM TWO INDEPENDENT NIH-FUNDED RESEARCH PROGRAMS WILL BE LEVERAGED TO MEET THESE AIMS, INCLUDING THE ADOLESCENT BRAIN COGNITIVE DEVELOPMENT (ABCD) STUDY AND THE CHAMBERS' COLLABORATIVE INITIATIVE ON FETAL ALCOHOL SPECTRUM DISORDERS (CIFASD) U01 PROJECT. THESE DISTINCT COHORTS PROVIDE A RARE OPPORTUNITY FOR ACCELERATION OF LEARNING OPPORTUNITIES AS WELL AS THE OPPORTUNITY TO IDENTIFY FACTORS THAT MODULATE THE RELATIONSHIP BETWEEN PHYSICAL ACTIVITY AND OUTCOME. IN ADDITION TO THE CLINICAL RESEARCH AIMS, THIS PROJECT WILL ASSESS THE ABILITY OF EXERCISE TO MITIGATE BEHAVIORAL AND COGNITIVE ALTERATIONS AND IMMUNE AND NEUROTROPHIC ACTIVITY IN A RODENT MODEL OF PAE, WHICH WILL BETTER OUR UNDERSTANDING OF PHYSICAL ACTIVITY AS AN INTERVENTION FOR FASD. THUS, THIS PROJECT WILL IMPROVE OUR UNDERSTANDING OF PHYSICAL ACTIVITY IN INDIVIDUALS WITH FASD AND BEGIN TO EXPLORE PHYSICAL ACTIVITY AS A POTENTIAL INTERVENTION TO LESSEN THE COGNITIVE AND EMOTIONAL CHALLENGES EXPERIENCED BY CHILDREN AND ADOLESCENTS WITH FASD, AS IN LINE WITH NIAAA STRATEGIC PLAN. WITH GUIDANCE FROM A STRONG MENTORSHIP TEAM, THIS HIGHLY PROPOSAL IS HIGHLY INNOVATIVE BY BRIDGING BASIC AND CLINICAL SCIENCE, AND ADDRESSING ISSUES THAT RANGE FROM IDENTIFICATION OF THE RELATIONSHIP OF EXERCISE AND CLINICAL OUTCOME TO MECHANISTIC STUDIES EVALUATING THE EFFECTIVENESS OF EXERCISE AS AN INTERVENTION. AT THE CONCLUSION OF THIS AWARD, THE CANDIDATE WILL MEET HER GOAL OF CAREER INDEPENDENCE AS A BIDIRECTIONAL TRANSLATIONAL INVESTIGATOR WITH EXPERTISE INVESTIGATING POTENTIAL INTERVENTIONS FOR SYMPTOMS OF FASD WITH BOTH PRECLINICAL AND CLINICAL RESEARCH.