NEURAL CIRCUITS UNDERLYING POST-OPERATIVE DELIRIUM IN EARLY STAGE ALZHEIMER'S DISEASE - POSTOPERATIVE DELIR…
Federal financial assistance recorded from USAspending. This is not a procurement contract.
Assistance award details
- Assistance award identifier
- ASST_NON_R00AG076877_075
- FAIN
- R00AG076877
- Recipient
- THE GENERAL HOSPITAL CORPORATION
- Awarding agency
- Department of Health and Human Services
- Funding agency
- Department of Health and Human Services
- Assistance listing (CFDA)
- 93.866
- Total obligated
- $493,019
- Period
- Dec 15, 2022 – Apr 30, 2028
- Fiscal year
- 2025
- Place of performance state
- MA
- Source file
- FY2025_All_Assistance_Full_20261006.zip
Description
NEURAL CIRCUITS UNDERLYING POST-OPERATIVE DELIRIUM IN EARLY STAGE ALZHEIMER'S DISEASE - POSTOPERATIVE DELIRIUM (POD) IS A COMMON AND SERIOUS POSTOPERATIVE COMPLICATION AMONG THE ELDERLY, ESPECIALLY THOSE WITH ALZHEIMERâS DISEASE (AD), AND HAS NO AVAILABLE TREATMENTS. INTERESTINGLY, THE RISK FOR POD BEGINS AT PRECLINICAL AD STAGES WHEN MILD SUSTAINED ATTENTION DEFICITS EMERGE. FOR THIS K99/R00, I WILL INVESTIGATE THE ROLE OF THE LOCUS COERULEUS AND VENTRAL TEGMENTAL AREA â TWO REGIONS AFFECTED BY AD PATHOLOGY AND INHIBITED BY GENERAL ANESTHETICS â ON THE DEVELOPMENT OF SUSTAINED ATTENTION DEFICITS AND POD USING THE RODENT MODEL OF AD, TGF344-AD. I HAVE DEVELOPED A VARIANT OF THE 5-CHOICE SERIAL REACTION TIME TASK, A TOUCHSCREEN SUSTAINED ATTENTION TASK, IN WHICH REAL-TIME COGNITIVE RECOVERY IS ASSESSED IN RATS FOLLOWING GENERAL ANESTHESIA TO CAPTURE THE SEVERITY AND DURATION OF POD SYMPTOMS. IN AIM 1 (K99), I WILL CHARACTERIZE THE PROGRESSION OF SUSTAINED ATTENTION DEFICITS IN TGF344-AD AND AGING RATS AND ITS ASSOCIATION WITH POD AND AD HISTOPATHOLOGY. IN AIM 2.1 (K99), I WILL USE A NOVEL DUAL-VIRAL MEDIATED CHEMOGENETIC TARGETING TECHNIQUE TO ESTABLISH THE ROLE OF VENTRAL TEGMENTAL AREA DOPAMINERGIC NEURONS IN AD-RELATED ATTENTIONAL IMPAIRMENTS. WITH THESE SKILLS, I WILL BE WELL- EQUIPPED TO INDEPENDENTLY PURSUE AIM 2.2 (R00), WHICH APPLIES THE SAME TECHNIQUES TO INVESTIGATE NORADRENERGIC LOCUS COERULEUS NEURONS IN AD-RELATED ATTENTION IMPAIRMENTS, AND AIM 3 (R00), WHERE CHRONIC AND ACUTE ACTIVATION OF THE VENTRAL TEGMENTAL AREA AND LOCUS COERULEUS WILL BE USED TO MITIGATE AD-ASSOCIATED POD. MY OVERALL CAREER GOAL IS TO LEAD AN INDEPENDENT RESEARCH GROUP EXAMINING THE UNDERLYING NEURAL CIRCUITS IMPACTING POD IN AD WITH THE LONG-TERM GOAL OF CREATING INTERVENTIONAL THERAPEUTIC STRATEGIES AGAINST DEMENTIA- ASSOCIATED POD. TO ACCOMPLISH THIS GOAL, I WILL NEED ADDITIONAL TRAINING IN CHEMOGENETIC TECHNIQUES, TRANSGENIC RODENT MODELS OF AD, AND AD NEUROPATHOLOGY. FO