Date of Graduation

5-2025

Document Type

Thesis

Degree Name

Bachelor of Science

Degree Level

Undergraduate

Department

Health, Human Performance and Recreation

Advisor/Mentor

Rosa-Caldwell, Megan

Committee Member

Murach, Kevin

Abstract

Background: Anorexia Nervosa (AN) is a psychiatric eating disorder that causes serious health consequences due to nutrient deprivation. Because of this, it has been associated with disrupted hypothalamic (HPT) function and changes to brain morphology. Rat models can be useful to understand the physiological consequences of AN both during the disease and after weight recovery. Purpose: Use MRI analysis and PCR testing to investigate brain matter volume alterations and HPT hormone synthesis alterations during simulated AN and following weight recovery. Methodology: Female Sprague Dawley rats (n= 66, 11/group, 8 weeks old) underwent simulated AN for 30 days with 50-60% food restriction. Recovery stages included no recovery (AN), 5 days (AN-5R) or 15 days (AN-15R), and 30 days (AN-30R). Short-term recovery groups were compared to an age-matched control (CON), and long-term recovery groups were compared to CON-30R. HPT tissue was collected and stored in -80°C post-euthanasia. MKRN3, Kiss1, TAC3, PDYN, GNRH, and Leptin Receptor genes were analyzed using RNA extraction and PCR testing, normalized to Rn45. MRI was performed immediately after euthanasia. ImageJ software quantified total brain volume (TBV), gray matter volume (GMV), white matter volume (WMV), and CSF volume. Short-term recovery data were analyzed by 1-way ANOVA with a Dunnett’s post-hoc test; long-term recovery data were analyzed by a T-test (p< 0.05). Results: The contents of genes present in the HPT for both short and long-term recovery groups were not statistically significant compared to the control groups (p>0.05). The MRI data posed statistical significance for alterations in GMV during short-term recovery (68316 + 1004.14 v. 74919 + 1073.47 v. 71194 + 1004.14 v. 73146 + 898.13 mm3, p= 0.0006) and WMV during long-term recovery (6157.27 + 365.03 v. 7507.73 + 365.03 mm3, p= 0.0165). TBV approached significance during short-term recovery but fell short (80416 + 1104.65 v. 83407 + 1235.03 v. 83230 + 1235.03 v. 84695 + 1053.24 mm3, p= 0.0594). Discussion: No significant changes HPT gene content suggest normal function of the HPT. There was high variability amongst these groups which could indicate factors like individual weight status, stage of estrous cycle, or another unknown variable causing this variability. MRI data showed a significant decrease in GMV, consistent with previous studies, indicating potential issues in decision-making and self-perception in individuals with AN. WMV was reduced following weight recovery suggesting possible long-lasting complications of the brain’s communication processes in those with a prior history with AN. Premature aging is also a concern as brain matter is shown to decrease with age. Investigating the short- and long-term complications associated with AN can help progress the understanding and development of possible therapeutic interventions.

Keywords

Anorexia Nervosa; Brain Matter; Hypothalamus Hormone Function; Weight Recovery

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