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Altered expression of the voltage-gated calcium channel subunit α2δ-1: a comparison between two experimental models of epilepsy and a sensory nerve ligation model of neuropathic pain.

Nieto-Rostro, M; Sandhu, G; Bauer, CS; Jiruska, P; Jefferys, JG; Dolphin, AC; (2014) Altered expression of the voltage-gated calcium channel subunit α2δ-1: a comparison between two experimental models of epilepsy and a sensory nerve ligation model of neuropathic pain. Neuroscience , 283 pp. 1224-137. 10.1016/j.neuroscience.2014.03.013. Green open access

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Abstract

The auxiliary α2δ-1 subunit of voltage-gated calcium channels is up-regulated in dorsal root ganglion neurons following peripheral somatosensory nerve damage, in several animal models of neuropathic pain. The α2δ-1 protein has a mainly presynaptic localization, where it is associated with the calcium channels involved in neurotransmitter release. Relevant to the present study, α2δ-1 has been shown to be the therapeutic target of the gabapentinoid drugs in their alleviation of neuropathic pain. These drugs are also used in the treatment of certain epilepsies. In this study we therefore examined whether the level or distribution of α2δ-1 was altered in the hippocampus following experimental induction of epileptic seizures in rats, using both the kainic acid model of human temporal lobe epilepsy, in which status epilepticus is induced, and the tetanus toxin model in which status epilepticus is not involved. The main finding of this study is that we did not identify somatic overexpression of α2δ-1 in hippocampal neurons in either of the epilepsy models, unlike the upregulation of α2δ-1 that occurs following peripheral nerve damage to both somatosensory and motor neurons. However, we did observe local reorganisation of α2δ-1 immunostaining in the hippocampus only in the kainic acid model, where it was associated with areas of neuronal cell loss, as indicated by absence of NeuN immunostaining, dendritic loss, as identified by areas where microtubule-associated protein-2 immunostaining was missing, and reactive gliosis, determined by regions of strong OX42 staining.

Type: Article
Title: Altered expression of the voltage-gated calcium channel subunit α2δ-1: a comparison between two experimental models of epilepsy and a sensory nerve ligation model of neuropathic pain.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.neuroscience.2014.03.013
Publisher version: http://dx.doi.org/10.1016/j.neuroscience.2014.03.0...
Additional information: Crown copyright © 2014 Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/3.0/).
Keywords: Alpha2delta subunit, Calcium channel, Dorsal root ganglion (DRG), Epilepsy, Neuropathic pain, Reactive gliosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: https://discovery.ucl.ac.uk/id/eprint/1424822
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