Altered ionic currents and amelioration by IGF-1 and PACAP in motoneuron-derived cells modelling SBMA

Autor: Carlo Musio, María José Polanco, Maria Pennuto, Leon J. Juárez-Hernández, Aura M. Jiménez Garduño, Laura Tosatto, Daniele Arosio, Manuela Basso, Daniela Michelatti
Rok vydání: 2017
Předmět:
0301 basic medicine
Patch-Clamp Techniques
Mutant
Cell
Action Potentials
PACAP
Biochemistry
Androgen
Mice
0302 clinical medicine
Models
Receptors
Insulin-Like Growth Factor I
Motor Neurons
Chemistry
Depolarization
Muscular Disorders
Atrophic
Cell biology
medicine.anatomical_structure
Receptors
Androgen
Tandem Repeat Sequences
Dihydrotestosterone
IGF-1
Pituitary Adenylate Cyclase-Activating Polypeptide
Motor neuron-derived cells
medicine.drug
medicine.medical_specialty
Ionic currents
Biophysics
Models
Biological
Cell Line
Polyglutamine diseases
03 medical and health sciences
Internal medicine
medicine
Animals
Humans
Patch clamp
IGF-1 and PACAP
Atrophic
Spinal and bulbar muscular atrophy (SBMA)
Organic Chemistry
Motor neuron
Biological
medicine.disease
Patch-clamp
Calcium
Peptides
Potassium
Androgen receptor
Muscular Disorders
Spinal and bulbar muscular atrophy
030104 developmental biology
Endocrinology
030217 neurology & neurosurgery
Zdroj: Biophysical chemistry
229 (2017): 68–76. doi:10.1016/j.bpc.2017.05.003
info:cnr-pdr/source/autori:Jiménez Garduño AM, Juárez-Hernández LJ, Polanco MJ, Tosatto L, Michelatti D, Arosio D, Basso M, Pennuto M, Musio C/titolo:Altered ionic currents and amelioration by IGF-1 and PACAP in motoneuron-derived cells modelling SBMA./doi:10.1016%2Fj.bpc.2017.05.003/rivista:Biophysical chemistry (Print)/anno:2017/pagina_da:68/pagina_a:76/intervallo_pagine:68–76/volume:229
ISSN: 0301-4622
Popis: Spinal and bulbar muscular atrophy (SBMA), also known as Kennedy's disease, is a motor neuron disease caused by the expansion of a polymorphic CAG tandem repeat encoding a polyglutamine (polyQ) tract in the androgen receptor (AR) gene. SBMA is triggered by the binding of mutant AR to its natural ligands, testosterone and dihydrotestosterone (DHT). To investigate the neuronal alterations of motor neuron cell models of SBMA, we applied patch-clamp methods to verify how polyQ expansions in the AR alter cell ionic currents. We used mouse motoneuron-derived MN-1 cells expressing normal AR (MN24Q) and mutant AR (MN100Q treated cells with vehicle EtOH and DHT). We observed a reduction of the current flux mainly at depolarizing potentials in the DHT-treated cells, while the dissection of macroscopic currents showed single different cationic currents belonging to voltage-gated channels. Also, we treated the cells with IGF-1 and PACAP, which have previously been shown to protect MN-1 cells from the toxicity of mutant AR, and we found an amelioration of the altered currents. Our results suggest that the electrophysiological correlate of SBMA is a suitable reference point for the identification of disease symptoms and for future therapeutic targets.
Databáze: OpenAIRE
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