Microglia Morphological Changes in the Motor Cortex of hSOD1G93A Transgenic ALS Mice.

Sara Migliarini,Silvia Scaricamazza,Alberto Ferri,Massimo Pasqualetti,Elisabetta Ferraro,Cristiana Valle

doi:10.3390/brainsci11060807

Sara Migliarini, Silvia Scaricamazza + Show 4 more

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https://doi.org/10.3390/brainsci11060807

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Abstract

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of spinal motor neurons as well as corticospinal (CSN) large pyramidal neurons within cortex layer V. An intense microglia immune response has been associated with both upper and lower motor neuron degeneration in ALS patients, whereas microgliosis occurrence in the motor cortex of hSOD1G93A mice—the best characterized model of this disease—is not clear and remains under debate. Since the impact of microglia cells in the neuronal environment seems to be crucial for both the initiation and the progression of the disease, here we analyzed the motor cortex of hSOD1G93A mice at the onset of symptoms by the immunolabeling of Iba1/TMEM119 double positive cells and confocal microscopy. By means of Sholl analysis, we were able to identify and quantify the presence of presumably activated Iba1/TMEM119-positive microglia cells with shorter and thicker processes as compared to the normal surveilling and more ramified microglia present in WT cortices. We strongly believe that being able to analyze microglia activation in the motor cortex of hSOD1G93A mice is of great importance for defining the timing and the extent of microglia involvement in CSN degeneration and for the identification of the initiation stages of this disease.

Highlights

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by degeneration of the motor neuron circuitry; both spinal/bulbar motor neurons (SMN) and motor cortex corticospinal/corticobulbar neurons (CSN-Betz cells in humans) are affected
Motor Cortex Microglia Cell Number Does Not Change in hSOD1G93A Mice Compared to WT Animals
As the occurrence and the features of cortical microgliosis in the ALS mouse model hSOD1G93A remain an open question, we performed a confocal analysis of motor cortex

Summary

Introduction

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by degeneration of the motor neuron circuitry; both spinal/bulbar (lower) motor neurons (SMN) and motor cortex corticospinal/corticobulbar (upper) neurons (CSN-Betz cells in humans) are affected. This is associated with progressive skeletal muscle atrophy and weakness, followed by complete paralysis and death [1]. Cortical hyperexcitability is typical of ALS patients and has been proposed to lead to glutamatergic excitotoxicity to downstream targets such as SMN, providing a possible mechanism for disease propagation [4] This might be associated with a loss of inhibitory GABAergic interneurons in the primary motor cortex, which might account for hyperexcitability [5]. Motor cortex hyperexcitability has been recorded prior to disease onset, and TDP-43 aggregates—another pathological hallmark of the disease—are mainly found in the motor cortex in post-mortem specimens, all features suggesting a primary cortical involvement in disease initiation [6,7]

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