Elsevier

Neuroscience

Volume 283, 26 December 2014, Pages 124-137
Neuroscience

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

https://doi.org/10.1016/j.neuroscience.2014.03.013Get rights and content
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Highlights

  • The calcium channel subunit α2δ-1 binds the antiepileptic drug gabapentin.

  • We examined if α2δ-1 was altered in two animal models of temporal lobe epilepsy.

  • In the kainate model there was local reorganization of α2δ-1 immunostaining.

  • This was associated with areas of hippocampal neuronal loss and reactive gliosis.

  • Unlike in neuropathic pain models, α2δ-1 did not increase in these epilepsy models.

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 reorganization 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.

Abbreviations

CaV
voltage-gated calcium
DAPI
4′,6-Diamidino-2-Phenylindole
DRG
dorsal root ganglion
EtOH
ethanol
HIV
human immunodeficiency virus
MAP2
microtubule-associated protein-2
PB
phosphate buffer
PBS
phosphate-buffered saline
PSNL
partial sciatic nerve ligation
SNL
spinal nerve ligation

Key words

calcium channel
dorsal root ganglion (DRG)
alpha2delta subunit
epilepsy
neuropathic pain
reactive gliosis

Cited by (0)

Current address: Department of Biomedical Science, University of Sheffield, Sheffield S10 2TN, UK.

Current address: Department of Developmental Epileptology, Institute of Physiology, Academy of Sciences of Czech Republic, Prague CZ-14220, Czech Republic.