Cognitive Impairment Comes Before Motor Degeneration in ALS, Study Shows

A research team led by Diego Minciacchi of the University of Florence in Italy identified a population of neurons that might explain the cognitive alterations antecedent to motor symptoms in Amyotrophic Lateral Sclerosis (ALS). The study entitled, “Increased anxiety-like behavior and selective learning impairments are concomitant to loss of hippocampal interneurons in the presymptomatic SOD1(G93A) ALS mouse model” appears online in the Journal of Comparative Neurology on February 16, 2015.

ALS is a neurodegenerative disease mainly characterized by loss of motor function caused by degeneration of motor neurons in a brain specific region (brain stem) and spinal cord. Other affected brain regions may explain why 50% of ALS patients also display cognitive deficits, and at least 15% have dementia.

Using an mouse model that reproduces clinical features of human ALS, researchers assessed cognitive function before general motor activity was impaired (presymptomatic mice). They performed two types of tests: open-field (OFT) and Barnes maze (BMT). In the first test, each mouse is placed in the center of an arena and allowed to explore the environment. The distance traveled and the percentage of time spent in the different sectors are recorded.

Presymptomatic mice explore mainly the periphery of the arena associated with anxiety-like behavior. The Barnes maze test is used to investigate spatial learning dependent on a specific brain region, the hippocampus. The maze consisted of a circular platform with 20 equally spaced holes along the periphery. One of the holes had a ramp to access a box (“escape box”) — rodents have aversion to open spaces and seek the confined box — in which the mouse could hide. Geometric figures are placed around the room, providing intentional visual cues for mice to find the escape box. Various parameters are measured including path length, number of errors, and velocity.

Using these parameters, the researchers concluded that presymptomatic mice displayed abnormal spatial memory. The research team found that behavior alterations were associated with the loss of neurons crucial to neuronal circuits establishment and hippocampal physiology. The main reduction of these neurons occurred before the onset of motor symptoms.

“We think that our work shed further light on the mechanisms of dysfunctions and the networks affected well before the onset of symptoms in murine ALS. Further research in this direction will potentially lead to the development of neuropsychological tests to assess hippocampus functions,” the authors concluded.