title: Calretinin and Neuropeptide Y interneurons are differentially altered in the motor cortex of the SOD1G93Amouse model of ALS.
abstract: Increasing evidence indicates an excitatory/inhibitory imbalance may have a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Impaired inhibitory circuitry is consistently reported in the motor cortex of both familial and sporadic patients, closely associated with cortical hyperexcitability and ALS onset. Inhibitory network dysfunction is presumably mediated by intra-cortical inhibitory interneurons, however, the exact cell types responsible are yet to be identified. In this study we demonstrate dynamic changes in the number of calretinin- (CR) and neuropeptide Y-expressing (NPY) interneurons in the motor cortex of the familial hSOD1G93AALS mouse model, suggesting their potential involvement in motor neuron circuitry defects. We show that the density of NPY-populations is significantly decreased by ~17% at symptom onset (8 weeks), and by end-stage disease (20 weeks) is significantly increased by ~30%. Conversely, the density of CR-populations is progressively reduced during later symptomatic stages (~31%) to end-stage (~36%), while CR-expressing interneurons also show alteration of neurite branching patterns at symptom onset. We conclude that a differential capacity for interneurons exists in the ALS motor cortex, which may not be a static phenomenon, but involves early dynamic changes throughout disease, implicating specific inhibitory circuitry.
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, 7000, Australia.
authors.forename: Rosemary M
authors.initials: RM
authors.lastname: Clark
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, 7000, Australia.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Blizzard
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, 7000, Australia.
authors.forename: Kaylene M
authors.initials: KM
authors.lastname: Young
authors.affiliation: Wicking Dementia Research &Education Centre2, University of Tasmania, Hobart, 7000, Australia.
authors.forename: Anna E
authors.initials: AE
authors.lastname: King
authors.affiliation: Menzies Institute for Medical Research, University of Tasmania, Hobart, 7000, Australia.
authors.forename: Tracey C
authors.initials: TC
authors.lastname: Dickson
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D064032:Calbindin 2 / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D007395:Interneurons / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009044:Motor Cortex / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D009478:Neuropeptide Y / Q000235:genetics*; D000072105:Superoxide Dismutase-1 / Q000235:genetics*
chemical_list: C576511:Calb2 protein, mouse; D064032:Calbindin 2; D009478:Neuropeptide Y; C000606290:SOD1 protein, human; D000072105:Superoxide Dismutase-1