Sex-Specific Contrasting Role of BECLIN-1 Protein in Pain Hypersensitivity and Anxiety-Like Behaviors

Disruption of BECLIN-1 enhances thermal pain hypersensitivity in male but not female Bcl2^AAA mice. A, Hot plate latency measures in female and male WT and Bcl2^AAA naive mice; no differences were observed. B, Hot plate latency measures in female and male WT and Bcl2^AAA mice exposed to SNI and sham surgery. Female and male WT and Bcl2^AA mice exposed to SNI showed significantly shorter response latencies compared with sham controls. Male, but not female, Bcl2^AAA mice showed significantly shorter response latencies compared with WT SNI mice. Three-way ANOVA, n = 10–15 per group; *p < 0.05, ***p < 0.001.

Disruption of BECLIN-1 prevents SNI-induced increases in anxiety-like behavior in the EPM in male mice. A, % time spent exploring the open arms of an EPM by SNI and sham-treated female and male WT and Bcl2^AAA mice. Whereas male WT mice showed a significant reduction in open arm exploration compared with sham-treated mice, male Bcl2^AAA mice showed no reductions in open arm exploration. B, Total entries displayed by mice in A. C, Representative heat maps of female (left) and male (right) mice exploration during EPM tests. Three-way ANOVA, n = 10–12 per group; *p < 0.05.

Disruption of BECLIN-1 prevents SNI-induced increases in anxiety-like behavior in the open field test in male mice. A, % time spent in the center area of an open field arena by female and male WT and Bcl2^AAA SNI and sham-treated mice. Male SNI Bcl2^AAA mice showed similar exploration time of the center area in the open field test compared with sham-treated controls. B, Total distance traveled by male WT and Bcl2^AAA mice in an OFT 30–31 d after SNI and sham surgery. C, Representative heat maps of female (left) and male (right) mouse exploration during open field tests. Three-way ANOVA, n = 10–12 per group; *p < 0.05.