An Astrocyte Regenerative Response from Vimentin-Containing Cells in the Spinal Cord of Amyotrophic Lateral Sclerosis's Disease-Like Transgenic (G93A SOD1) Mice

Abstract

The reason for regeneration in the adult spinal cord during motor neuron degeneration in amyotrophic lateral sclerosis (ALS) remains largely unknown. To this end, we studied the alteration of vimentin (a neural precursor cells marker in CNS)-containing cells (VCCs) in spinal cord during different stages of ALS used C57BL/6J G93A SOD1 transgenic mice mimicking ALS. Results showed that VCCs were mostly distributed in the ependymal zone (EZ) surrounding the central canal of spinal cord in SOD1 wild type mice; a few of VCCs were sparsely distributed in other regions. However, the number of VCCs significantly increased in the spinal cord during the onset and progression stages of ALS. They were extensively distributed in the EZ, the anterior, the lateral and the posterior horn of grey matter, particularly in the posterior horn region at the progression stage. A majority of VCCs in the anterior, the lateral and the posterior horn of grey matter (outside of EZ) generated astrocytes, but no neurons, oligodendrocytes and microgliocytes. Our results suggested that there was a potential astrocyte regenerative response to motor neuron degeneration in motor neurons-degenerated regions in the adult spinal cord during the onset and progression stages of ALS-like disease. The regenerative responses in the adult spinal cord of ALS-like mice may be a potential pathway in attempting to repair the degenerated motor neurons and restore the dysfunctional neural circuitry.

The Overexpression of TDP-43 Protein in the Neuron and Oligodendrocyte Cells Causes the Progressive Motor Neuron Degeneration in the SOD1 G93A Transgenic Mouse Model of Amyotrophic Lateral Sclerosis

“…The muscle pathologic results were the same as that in our previous published paper 14, which further confirmed the divide of different stages in our experiments.…”

“…At the different stages of disease, the gastrocnemius muscle of abnormal limb was taken to perform the HE staining, to observe the alterations of muscle structure and morphology in the light microscope in order to identifying the paralytic severity of limb muscle and further deciding the disease courses of pre-onset, onset and progression. All experimental protocols were the same as our previous published paper 14. All animal studies and experiments were performed in accordance with the guide for the care and use of laboratory animals, and were reviewed and approved by the ethics committee for animal care and use of the First Affiliated Hospital of Nanchang University, China.…”

Distributed Features of Vimentin-Containing Neural Precursor Cells in Olfactory Bulb of SOD1G93A Transgenic Mice: a Study about Resource of Endogenous Neural Stem Cells

“…The experimental animals were sacrificed at the time points of pre-onset (60-70d), onset (90-100 d) and progressive (120-130 d) stages of SOD1 G93A transgenic mice and the age-matched wild-type mice. At the different stages of disease, the gastrocnemius muscles of the abnormal limb were performed the HE stain, observed the alterations of muscle structure in the light microscope, further confirmed the severity of muscle atrophy in the paralysis limb and distinguished the disease stages of pre-onset, onset and progression 34, 36-38. The protocol of muscle biopsy was the same as the descriptions in our previously published paper 34.…”

“…We screened and determined the C57BL/6J SOD1 G93A positive transgenic mice by the PCR of genomic DNA and the muscle biopsy which were the same as our previous published paper 34. In our breeding SOD1 G93A transgenic mice, we observed the typical characteristics of ALS-like symptoms at the pre-onset (60-70 d), onset (90-100 d) and progression (120-130 d) stages in the ALS-like disease courses.…”

“…In our previous studies, we found that the endogenous neural precursor cells (NPCs) could proliferate, differentiate and migrate to the damaged regions of spinal cord, produce the novel neural cells including neuron and glial cells, partially repair the neuron lesion in the SOD1 G93A transgenic mice, but the repair ability was very less, could not effectively ameliorate or prevent the disease development 10, 11, 34. In view of this, we speculated that if the mechanism of the proliferation, differentiation and migration of endogenous NPCs in the pathological conditions of ALS could be elucidated, it would bring the possibility to us to regulate the proliferation, differentiation and migration of endogenous NPCs, promote the self-recovering ability, enhance its neural repair function, improve the self-repair ability of the neural functional lesions in ALS, ameliorate or prevent from the development of ALS, and also could avoid the deficiency of the exogenous stem cell transplantation, would be a potential novel ideal way to ameliorate or prevent from the development of ALS besides the transplantation of exogenous stem cell.…”