VCOM Louisiana Research Day Program Book 2024

Biomedical Research: Section 1

Sabeen Wazir, OMS-I; Brina Snyder, PhD; Thomas Floyd, MD VCOM-Louisiana; UTSW Medical Center 9 OPTIMIZATION OF PARADIGMS FOR ASSESSING COGNITIVE PERFORMANCE WITHIN A HYPOXIC ENVIRONMENT

Background: Chronic Obstructive Pulmonary Disease, anemia, and obstructive sleep apnea are examples of chronic hypoxic conditions that often adversely affect aging populations and are associated with cognitive impairment. The gold-standard for assessing cognitive outcomes has been behavioral testing paradigms in rodent models. However, their usage in understanding chronic hypoxic conditions has been hindered by the inability to perform these tests under stable hypoxic conditions. Changes to behavior tests impact the validity of the paradigm. Objective: We present validated testing paradigms that can be performed in hypoxic chambers to model hypoxia-inducing diseases and allow for better understanding of chronic conditions. Methods: 3 month old (3 mo) wild-type male and female C57Bl6/J mice (n=6 each sex) were housed, trained and tested within enclosed hypoxia chambers from Biospherix, Ltd. Spontaneous Alternation (SA) and Spatial Object Recognition (SOR) paradigms were selected as tests of working memory. Mice were housed and acclimated to specific oxygen (O2) conditions in one chamber and transferred to a separate chamber for testing under the same O2 level. Following one day of acclimation to either 21%

or 15% oxygen, protocols were conducted as outlined in D’Isa, et al., 2021 (SA) and Leger, et at., 2013 (SOR). Animal movements and interactions were tracked using an overhead camera and EthoVision tracking software. To determine validity, thresholds for chance were set at greater than 50% alternation over 7 trials for SA, and greater than 60% novel location and 0.25 D.I. for SOR. The total number of object contacts in a familiar and a novel location were quantified and used to calculate the percentage of contacts in the novel location and a discrimination index (D.I.) using the following formulas: % novel = (# novel contacts / total number of contacts) * 100 and D.I. = (# novel contacts - # familiar contacts) / total # contacts. Results: In SA, 3 mo mice exhibited a percentage of alternation 61.11%, which is above the expected threshold for chance. As expected, testing under 15% O2 reduced alternation to 33.33%. In the SOR, both the % novel (66.57%) and D.I. (0.33) were also above chance for 3 mo normoxic control mice. The results indicate both the SA and SOR paradigms can be adapted to assess behavior under mild moderate hypoxic conditions. Conclusions: In conclusion, these paradigms more accurately mimic cognitive performance

and functional conditions for people who suffer from chronic hypoxic conditions.

21 2024 Via Research Recognition Day