Spinal Inhibitory Interneuron Pathology Follows Motor Neuron Degeneration Independent of Glial Mutant Superoxide Dismutase 1 Expression in SOD1-ALS Mice
| Autor: | Elize D. Haasdijk, Vera van Dis, Sebastian Cardona Cano, Casper C. Hoogenraad, Jan C. Holstege, Dick Jaarsma, Mehdi Hossaini |
|---|---|
| Přispěvatelé: | Neurosciences |
| Rok vydání: | 2011 |
| Předmět: |
Calbindins
Pathology Proto-Oncogene Proteins c-jun Galectin 3 Mice Glycine Plasma Membrane Transport Proteins Amyotrophic lateral sclerosis Motor Neurons Denervation biology Glutamate Decarboxylase Age Factors General Medicine Parvalbumins medicine.anatomical_structure Spinal Cord Neurology Neuroglia medicine.medical_specialty Interneuron Green Fluorescent Proteins SOD1 Mice Transgenic Inhibitory postsynaptic potential Choline O-Acetyltransferase Pathology and Forensic Medicine Cellular and Molecular Neuroscience S100 Calcium Binding Protein G Interneurons medicine Animals Humans RNA Messenger Activating Transcription Factor 3 Superoxide Dismutase Ubiquitin Amyotrophic Lateral Sclerosis nutritional and metabolic diseases medicine.disease Spinal cord Disease Models Animal Gene Expression Regulation nervous system Mutation Nerve Degeneration Glycine transporter 2 biology.protein Neurology (clinical) Neuron Neuroscience |
| Zdroj: | Journal of Neuropathology and Experimental Neurology, 70(8), 662-677. Oxford University Press |
| ISSN: | 0022-3069 |
| Popis: | Motor neuron degeneration and skeletal muscle denervation are hallmarks of amyotrophic lateral sclerosis (ALS), but other neuron populations and glial cells are also involved in ALS pathogenesis. We examined changes in inhibitory interneurons in spinal cords of the ALS model low-copy Gurney G93A-SOD1 (G1del) mice and found reduced expression of markers of glycinergic and GABAergic neurons, that is, glycine transporter 2 (GlyT2) and glutamic acid decarboxylase (GAD65/67), specifically in the ventral horns of clinically affected mice. There was also loss of GlyT2 and GAD67 messenger RNA-labeled neurons in the intermediate zone. Ubiquitinated inclusions appeared in interneurons before 20 weeks of age, that is, after their development in motor neurons but before the onset of clinical signs and major motor neuron degeneration, which starts from 25 weeks of age. Because mutant superoxide dismutase 1 (SOD1) in glia might contribute to the pathogenesis, we also examined neuron-specific G93A-SOD1 mice; they also had loss of inhibitory interneuron markers in ventral horns and ubiquitinated interneuron inclusions. These data suggest that, in mutant SOD1-associated ALS, pathological changes may spread from motor neurons to interneurons in a relatively early phase of the disease, independent of the presence of mutant SOD1 in glia. The degeneration of spinal inhibitory interneurons may in turn facilitate degeneration of motor neurons and contribute to disease progression. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|