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.
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.
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK.
authors.forename: M
authors.initials: M
authors.lastname: Nieto-Rostro
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK.
authors.forename: G
authors.initials: G
authors.lastname: Sandhu
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK.
authors.forename: C S
authors.initials: CS
authors.lastname: Bauer
authors.affiliation: Neuronal Networks Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: P
authors.initials: P
authors.lastname: Jiruska
authors.affiliation: Neuronal Networks Group, School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK.
authors.forename: J G R
authors.initials: JG
authors.lastname: Jefferys
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, UK. Electronic address: a.dolphin@ucl.ac.uk.
authors.forename: A C
authors.initials: AC
authors.lastname: Dolphin
mesh_terms: D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D016923:Cell Death; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000150:complications / Q000473:pathology*; D005727:Ganglia, Spinal / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D005911:Gliosis / Q000209:etiology; D006624:Hippocampus / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity; D008026:Ligation / Q000009:adverse effects; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009437:Neuralgia / Q000150:complications / Q000209:etiology / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013744:Tetanus Toxin / Q000633:toxicity
chemical_list: D039481:CD11b Antigen; C486060:Cacna2d1 protein, rat; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D008869:Microtubule-Associated Proteins; D009498:Neurotoxins; D013744:Tetanus Toxin; D010751:Phosphopyruvate Hydratase; D007608:Kainic Acid
keywords: alpha2delta subunit; calcium channel; dorsal root ganglion (DRG); epilepsy; neuropathic pain; reactive gliosis