Affiliations: [a] Institute of Cell Biophysics, Russian Academy of Sciences, Pushchino, Russian Federation
| [b] Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russian Federation
| [c] School of Biosciences and Neuroscience & Mental Health Research Institute, Cardiff University, Cardiff, UK
| [d] Institute of Physiologically Active Compounds, Russian Academy of Sciences, Chernogolovka, Russian Federation
Correspondence:
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Correspondence to: Dr. Vasily Vorobyov, PhD, Institute of Cell Biophysics, Pushchino, 142290, Russian Federation. Tel.: +007 4967 739 442; Fax: +007 4967 330 509; E-mail: vorobyovv2@gmail.com.
Abstract: Background:Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons resulting in muscle atrophy. In contrast to the lower motor neurons, the role of upper (cortical) neurons in ALS is yet unclear. Maturation of locomotor networks is supported by dopaminergic (DA) projections from substantia nigra to the spinal cord and striatum. Objective:To examine the contribution of DA mediation in the striatum-cortex networks in ALS progression. Methods:We studied electroencephalogram (EEG) from striatal putamen (Pt) and primary motor cortex (M1) in ΔFUS(1–359)-transgenic (Tg) mice, a model of ALS. EEG from M1 and Pt were recorded in freely moving young (2-month-old) and older (5-month-old) Tg and non-transgenic (nTg) mice. EEG spectra were analyzed for 30 min before and for 60 min after systemic injection of a DA mimetic, apomorphine (APO), and saline. Results:In young Tg versus nTg mice, baseline EEG spectra in M1 were comparable, whereas in Pt, beta activity in Tg mice was enhanced. In older Tg versus nTg mice, beta dominated in EEG from both M1 and Pt, whereas theta and delta 2 activities were reduced. In younger Tg versus nTg mice, APO increased theta and decreased beta 2 predominantly in M1. In older mice, APO effects in these frequency bands were inversed and accompanied by enhanced delta 2 and attenuated alpha in Tg versus nTg mice. Conclusion:We suggest that revealed EEG modifications in ΔFUS(1–359)-transgenic mice are associated with early alterations in the striatum-cortex interrelations and DA transmission followed by adaptive intracerebral transformations.
Keywords: ALS progression, dopamine, EEG, frequency spectrum, primary motor cortex, putamen
