Neuroprotective Effect of σ1-Receptors on the Cell Model of Huntington's Disease

A V Bol'shakova; N A Kraskovskaya; A N Gainullina; E O Kukanova; O L Vlasova; I B Bezprozvanny

doi:10.1007/s10517-017-3968-7

Neuroprotective Effect of σ1-Receptors on the Cell Model of Huntington's Disease

Bull Exp Biol Med. 2017 Dec;164(2):252-258. doi: 10.1007/s10517-017-3968-7. Epub 2017 Nov 25.

Authors

A V Bol'shakova¹, N A Kraskovskaya², A N Gainullina¹, E O Kukanova¹, O L Vlasova¹, I B Bezprozvanny^{3

4}

Affiliations

¹ Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg State Polytechnic University, St. Petersburg, Russia.
² Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg State Polytechnic University, St. Petersburg, Russia. ninakraskovskaya@gmail.com.
³ Laboratory of Molecular Neurodegeneration, Peter the Great St. Petersburg State Polytechnic University, St. Petersburg, Russia. mnlabspb@gmail.com.
⁴ Department of Physiology, UT Southwestern Medical Center at Dallas, Dallas, USA. mnlabspb@gmail.com.

PMID: 29177899
DOI: 10.1007/s10517-017-3968-7

Abstract

Huntington's disease is a hereditary neurodegenerative disease that primarily affects striatal neurons. Recent studies demonstrated abnormalities in calcium regulation in striatal neurons in Huntington's disease, which leads to elimination of synaptic connections between cortical and striatal neurons. In the present study, we focused on the neuroprotective properties of σ1-receptor, because one of its main functions is associated with modulation of calcium homeostasis in cells. The application of selective σ1-receptor agonists to the corticostriatal cell culture restores synaptic connections between the cortical and striatal neurons. Based on the obtained data, we assume that σ1-receptor is a promising target for the development of drugs for the therapy of Huntington's disease.

Keywords: Huntington’s disease; cortico-striatal cell cultures; dendritic spines; medium spiny neurons; σ1-receptor.

MeSH terms

Animals
Anisoles / pharmacology
Calcium / metabolism*
Cerebral Cortex / metabolism
Cerebral Cortex / pathology
Corpus Striatum / metabolism
Dendritic Spines / metabolism
Dendritic Spines / pathology
Gene Expression
Homeostasis
Huntington Disease / genetics*
Huntington Disease / metabolism
Huntington Disease / pathology
Male
Mice
Models, Biological
Morpholines / pharmacology
Neurons / metabolism*
Neurons / pathology
Piperidines / pharmacology
Primary Cell Culture
Propylamines / pharmacology
RNA, Small Interfering / genetics
RNA, Small Interfering / metabolism
Receptors, sigma / agonists
Receptors, sigma / antagonists & inhibitors
Receptors, sigma / genetics*
Receptors, sigma / metabolism
Sigma-1 Receptor
Synapses / metabolism
Synapses / pathology
Synaptic Transmission / genetics*
Transduction, Genetic

Substances

Anisoles
Morpholines
Piperidines
Propylamines
RNA, Small Interfering
Receptors, sigma
2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate
N,N-dipropyl-2-(4-methoxy-3-(2-phenylethoxy)phenyl)ethylamine monohydrochloride
preclamol
Calcium