Monitoring of Brain Spiking Activity and Autoantibodies to N‐Terminus Domain of GluR1 Subunit of AMPA Receptors in Blood Serum of Rats with Cobalt‐Induced Epilepsy

Abstract

Abstract:We have monitored EEG spontaneous spiking activity and analyzed serum from rats with cobalt-induced epilepsy for the presence of autoreactive antibodies to a -amino -3-hydroxy -5-methylisoxazole -4-propionate (AMPA) glutamate receptor subunits. The presence and the level of autoantibodies were assessed using immunoblot and [LISA with synthetic peptide specific to the N-terminus domain of the GIuR1 subunit of the AMPA receptor. Rats with cobalt-induced epilepsy exhibited strong GIuR1 immunoreactivity at the end of the first week after surgery compared with vehicle-treated rats. We showed that GIuR1 autoantibodies in blood serum of rats with cobalt-induced epilepsy preceded the spiking activity maximum in the EEG. Levels of autoantibodies to GIuR1 detected in blood of these rats remained elevated when EEG spiking activity was significantly reduced and seizures disappeared. The EEG monitoring of spiking activity showed a correlation with accumulation of GluRl autoantibodies in blood serum of rats with cobalt-induced epilepsy.

Autoantibodies against opioid or glutamate receptors are associated with changes in morphine reward and physical dependence in mice

“…Peptide fragments of MDOR and GluR1 were used as antigens to detect serum aAbs levels by a modified enzymelinked immunosorbent assay (Dambinova et al , 1998. In brief, the diluted blood sera (1:50, 100 μl) were applied on the immunoplate (Costar, USA) containing the corresponding peptide (0.5 μg/well) and blocking agent.…”

“…Recent studies report that increased levels of autoantibodies (aAbs) to several central nervous system (CNS) antigens can be detected in the blood of patients with neuropsychiatric disorders as well as in experimental animal models (Vincent et al 1999;Kowal et al 2006;Zandman-Goddard et al 2007;Dambinova et al 1997Dambinova et al , 1998Knight et al 2007). Increased levels of aAbs to amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) or to N-methyl-D-aspartate (NMDA) receptors have been evidenced in the serum of patients with intractable seizures (Rogers et al 1994;Twyman et al 1995) or brain ischemic stroke (Dambinova et al 2003), respectively.…”

Overview of the Current Animal Models for Human Seizure and Epileptic Disorders

“…For example, focal application of antagonists for GABA receptors such as penicillin, bicuculline, and picrotoxin can act locally to disrupt the balance of inhibition and excitation and create an epileptogenic focus. Similarly, introduction of heavy metals such as aluminum (7,81), cobalt (82,83), zinc (84), and iron (85,86) into cortical areas can lead to the development of focal lesions and epileptogenicity. While these would be considered examples of simple partial seizures, a systemic injection of KA or PILO, and kindling of limbic regions (as described above) are reliable methods for producing a characteristic onset of complex partial seizures.…”

Detection of antibodies to opioid and glutamate receptors by latex agglutination and enzyme immunoassay

“…The content of autoantibodies to GluR1 and GluR3 glutamate receptor subunits increases in paroxysmal conditions of the brain, content of autoantibodies to NR2A glutamate receptor subunit increases in cerebral circulation disorders, and the levels of autoantibodies to µ-and δ-opioid receptors increase in opium narcomania [4,5,10,12]. These changes are presumably due to specific involvement of certain receptor proteins in the pathological process and their intense destruction and production of antibodies to the receptor fragments.…”