MicroRNA Profiling Reveals Marker of Motor Neuron Disease in ALS Models

• DOI: 10.1523/jneurosci.3582-16.2017
• Publication Date: 2017-04-18T00:35:19Z
• Authors: Mariah L. Hoye; Erica D. Koval; Amy J. Wegener; Theodore S. Hyman; Chengran Yang; David R. O'Brien; Rebecca L. Miller; Tracy Cole; Kathleen M. Schoch; Tao Shen; Tomonori Kunikata; Jean-Philippe Ric...; David H. Gutmann; Nicholas J. Marag...; Holly B. Kordasie...; Joseph D. Dougherty; Timothy M. Miller
• Keywords: Cell type

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder marked by the loss of motor neurons (MNs) in brain and spinal cord, leading to fatally debilitating weakness. Because this disease predominantly affects MNs, we aimed characterize distinct expression profile that cell type elucidate underlying mechanisms identify novel targets inform on MN health during ALS time course. microRNAs (miRNAs) are short, noncoding RNAs can shape thus often exhibit cell-type-enriched expression. To determine MN-enriched miRNA expression, used Cre recombinase-dependent tagging affinity purification mice. By defining vivo all neurons, astrocytes, microglia, then focused miRNAs via comparative analysis found they may functionally distinguish MNs postnatally from other neurons. Characterizing levels CSF harvested models demonstrated one (miR-218) tracked with was responsive an therapy rodent models. Therefore, have cellular profiling tools define which likely enrich future studies disease. This approach enabled development novel, drug-responsive marker rodents. SIGNIFICANCE STATEMENT cord selectively lost. develop aid our understanding profiles and, ultimately, monitor progression, identified small regulatory were highly enriched or exclusive MNs. The signal for these detectable tap biofluid rat model, where its change as progresses, suggesting it be clinically useful status. Furthermore, rats treated restored RNA marker, making MN-specific