Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with three described forms: The abundant, sporadic ALS (sALS) with approximately 90% of cases, the familial ALS (fALS) with 5-10%, and the very rare juvenile ALS (jALS) group, which is statistically less relevant. The wobbler mouse, a model for sALS, has been in the focus of research for many decades. Due to symptoms strongly resembling the human ALS pathology, the α-motor neurons (αMN) have received the most attention. With regard to pathological cellular processes, particularly those of impaired axonal transport, neuronal tissues in general should be examined. Dorsal root ganglia (DRG) cells are equipped with extremely long axons. Thus, we expected them to be an excellent target for analyzing the cellular mechanisms underlying the disease. In this study, an analysis of the distribution of heavy neurofilaments (NfH) in the perikarya and peripheral nerves of dorsal root ganglia cells from wobbler mice was performed. Here, we demonstrate that sensory neurons are also affected in wobbler mice during the progression of the disease, showing signs of degeneration like those described in the αMN. Furthermore, a highly impaired distribution of neurofilaments and a high number of phosphorylated heavy neurofilaments (pNfH) were observed, not only in large light neurons (LLN), but also in the small dark neurons (SDN) of wobbler mouse DRGs. The accumulation of pNfH in DRG as well as the loss of NfH in their axons are promising links to studies promoting high levels of pNfH in the cerebrospinal fluid (CSF) as an early hallmark of ALS in humans.
Citation: Ott B, Dahlke C, Saberi D, BrandSaberi B, Matschke V, et al. 2017. Morphological Studies of Wobbler Mouse Dorsal Root Ganglia Show Neurofilamental Disorders. J Neurol Exp Neurosci 3(1): 1-7.