1196-P: Perineuronal Nets in MeA and Arc Are Influenced by Gonadectomy

Abstract

Background: Recent studies reveal perineuronal nets (PNNs), extracellular matrix specializations that restrict the plasticity of neurons, are influenced by pubertal status. Here we show that PNN are changed by gonadectomy (GDX) both in male and female mice in medial amygdala (MeA) and arcuate nucleus (Arc). Method: 49 wild type mice are divided into 16 groups by sex, gonadectomy, diet, nutritional status (fed or fasted groups). Fat and lean body mass were assessed by QMR at baseline and before perfusion. Body weight, food intake, and blood glucose were measured weekly for five weeks. Images were captured in MeA, Arc, paraventricular hypothalamus (PVH), anterior hypothalamus (AH), and an intense WFA positive radial area near PVH, which we named ‘periPVH’ after labelling of Wisteria floribunda agglutinin (WFA). Results: In MeA region, female mice have significantly lower total fluorescence intensity (TFI) (Estimate, 95% Confidence Interval: –448887.02, –578807.10 – –318966.94; p <0.0001) and total number of PNNs (–319.67, –379.34258 – –259.99075: p<0.0001) than male mice. Notably, in female, OVX mice have lower mean fluorescence intensity (MFI) (Mean ± SD: 14.5 ± 3.3 vs. 19.6 ± 4.1; p = 0.003) and TFI (64907.8 (58406.6–96971.3) vs. 123613.9 (83545.9–149131.5); p = 0.015) than sham mice, while the total number of PNNs (Mean ± SD: 63 ± 23 vs. 55 ± 3; p = 0.391) shows no significant difference. Male castration mice have lower total number of PNNs (382 ± 141 vs. 55 ± 22; p <0.0001) and TFI (439343.5 (366431.4–787461.9) vs. 168416.3 (141273.0–258020.8); p <0.0001) than sham mice, while the MFI shows no significant difference. In Arc, mice experiencing GDX have significantly lower MFI (–3.63, –5.61303 – –1.63967; p <0.001), TFI (–28525.8, –45357.46 – –11694.16; P<0.01) or total number of PNNs (–15.3, –29.24 – –1.41; p =0.036) than mice not. PVH, AH, and periPVH don’t show associations with sex, GDX, diet or nutritional status in our observation. Summary: Our novel discovery indicates the potential role PNN might play in sex hormone regulation in brain. Disclosure N. Zhang: None. Y. Xu: None. Funding National Institutes of Health (R01DK117281)