The effect of estrogen therapy on cerebral metabolism in diabetic female rats

Chun-Yi Wu; Yu-Hsin Lin; Hsin-Hua Hsieh; Yi-Hsiu Chung; Shih-Ting Hsu; Shin-Lei Peng

doi:10.1016/j.csbj.2023.09.031

The effect of estrogen therapy on cerebral metabolism in diabetic female rats

Comput Struct Biotechnol J. 2023 Sep 25:21:4769-4776. doi: 10.1016/j.csbj.2023.09.031. eCollection 2023.

Authors

Chun-Yi Wu¹, Yu-Hsin Lin^{2

3}, Hsin-Hua Hsieh¹, Yi-Hsiu Chung⁴, Shih-Ting Hsu⁴, Shin-Lei Peng^{5

6}

Affiliations

¹ Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei Branch, Taipei, Taiwan.
² Department of Pharmacy, National Yang Ming Chiao Tung University, Taipei Branch, Taipei, Taiwan.
³ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
⁴ Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
⁵ Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan.
⁶ Neuroscience and Brain Disease Center, China Medical University, Taiwan.

Abstract

The impact of estrogen on brain function, especially in individuals with diabetes, remains uncertain. This study aims to compare cerebral glucose metabolism levels in intact rats, ovariectomized (OVX) rats, and 17β-estradiol (E2)-treated OVX diabetic female rats. Sixteen rats were administered a single intraperitoneal injection of 70 mg/kg streptozotocin (STZ) to induce diabetes (intact, n = 6; OVX, n = 6; OVX+E2-treated, n = 4). Additionally, 18 rats received an equivalent solvent dose via intraperitoneal injection (intact, n = 6; OVX, n = 6; OVX+E2-treated, n = 6). After 4 weeks of STZ or solvent administration, positron emission tomography scans with ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) injection were employed to assess cerebral glucose metabolism. The diabetic rats exhibited substantial reductions in ¹⁸F-FDG uptake across all brain regions (all P < 0.01), in contrast to the control rats. Moreover, intact and OVX + E2-treated diabetic female rats displayed more pronounced decreases in cerebral glucose metabolism in the amygdala and hippocampus compared to OVX diabetic female rats (P < 0.05). These findings suggest that diabetes creates an environment wherein estrogen exacerbates neuropathology and intensifies neuronal activity.

Keywords: 18F-fluorodeoxyglucose; Hyperglycemia; Neural activity; Ovariectomy; Streptozotocin.