Striatal Neurodegeneration that Mimics Huntington's Disease Modifies GABA-induced Currents.

Jorge Flores-Hernández,Elizabeth Nieto-Mendoza,Gustavo Hernández-Carballo,Elizabeth Hernández-Echeagaray,Jeanette Garzón-Vázquez,Evelyn Ruíz-Luna

doi:10.3390/brainsci8120217

Abstract

Huntington’s Disease (HD) is a degenerative disease which produces cognitive and motor disturbances. Treatment with GABAergic agonists improves the behavior and activity of mitochondrial complexes in rodents treated with 3-nitropropionic acid to mimic HD symptomatology. Apparently, GABA receptors activity may protect striatal medium spiny neurons (MSNs) from excitotoxic damage. This study evaluates whether mitochondrial inhibition with 3-NP that mimics the early stages of HD, modifies the kinetics and pharmacology of GABA receptors in patch clamp recorded dissociated MSNs cells. The results show that MSNs from mice treated with 3-NP exhibited differences in GABA-induced dose-response currents and pharmacological responses that suggests the presence of GABAC receptors in MSNs. Furthermore, there was a reduction in the effect of the GABAC antagonist that demonstrates a lessening of this GABA receptor subtype activity as a result of mitochondria inhibition.

Highlights

Huntingtons Disease (HD) is a genetic neurodegenerative disorder originated by a gene mutation which results in the degeneration of neurons mainly in the nucleus striatum
Half of the medium spiny neurons (MSNs) belonged to the control group and half to the group from mice treated with 3-nitropropionic acid (3-NP)
These results demonstrate that receptors with the α5 subunit are not altered as a result of the demonstrate that GABA receptors with the 5 subunit are not altered as a result of the damage damage produced by mitochondria inhibition

Summary

Introduction

Huntingtons Disease (HD) is a genetic neurodegenerative disorder originated by a gene mutation which results in the degeneration of neurons mainly in the nucleus striatum. The systemic administration of toxins or mitochondrial inhibitors, such as 3-nitropropionic acid (3-NP), produces movement disorders in primates and rodents [5,6,7,8,9] and cell damage that resembles the neuropathology observed in patients affected by HD [10,11,12]. This effect occurs because GABAergic striatal projection neurons (medium spiny neurons, MSNs) are vulnerable to mitochondrial dysfunction and excitotoxicity [1,13]. No cure for HD has been developed far; treatments are directed to attenuate symptomatology

Objectives

Methods

Results

Discussion

Conclusion