Fig. 9.

Histological evidence of degeneration within the hypoglossal nucleus and tract in advanced disease stage HCN-SOD1 and LCN-SOD1 mice. Left panel Representative hematoxylin-and eosin-stained sections from the hypoglossal nucleus region (black outline) in the brainstem of HCN-SOD1 (b) and LCN-SOD1 (c) mice at advanced disease stage, as well as an age-matched control (a) from our LCN colony. Axons from motor neurons in the hypoglossal nucleus project ventrally (red boxes) to form the hypoglossal tract and ultimately the hypoglossal nerve that innervates the tongue. Middle panel Higher magnification images of the hypoglossal nucleus within the white boxed regions in the left panel (a–c). Compared to controls (d), the hypoglossal nucleus of HCN-SOD1 (e) and LCN-SOD1 (f) mice had marked vacuolation (arrows) throughout the neuropil, a hallmark feature of mitochondrial pathology in SOD1 models of ALS. Right panel Higher magnification images of the hypoglossal tract within the red boxed regions in the left panel (a–c). hSOD1(+) lined vacuoles are abundant in the hypoglossal tracts of HCN-SOD1 (h) and LCN-SOD1 (i) mice but not controls (g). Note the larger size of the vacuoles for LCN-SOD1 mice compared to HCN-SOD1 mice in both the hypoglossal nucleus and tract. Asterisk = central canal