The extracellular matrix protein SC1/hevin localizes to excitatory synapses following status epilepticus in the rat lithium-pilocarpine seizure model.
The epileptic brain is characterized by increased susceptibility to neuronal hyperexcitability. The rat lithium-pilocarpine model, which mimics many features of temporal lobe epilepsy, has been used to study processes leading to the development of recurrent seizures. After a prolonged seizure episode, termed status epilepticus (SE), neural changes occur during a period known as epileptogenesis and include neuronal cell death, reactive gliosis, axonal sprouting, and synaptogenesis. Extracellular matrix adhesion molecules are important regulators of synaptogenesis and axonal sprouting resulting from SE. SC1, also known as hevin, is an antiadhesive extracellular matrix molecule that localizes to synapses in the mammalian brain. In this study, the distribution of SC1 protein in neurons following SE was examined using the lithium-pilocarpine model. SC1 protein levels in neuronal cell bodies showed a transient decrease at 1 day post-SE, which coincided with an increase of SC1 in the synapse-rich neuropil that was identified with the synaptic marker synaptophysin. Immunoelectron microscopy confirmed the decrease of SC1 signal in neurons at 1 day post-SE and showed that SC1 remained localized to postsynaptic elements throughout the seizure time course. Increased colocalization of SC1 was detected with the excitatory synaptic markers vesicular glutamate transporter 1 (VGLUT1), AMPA receptor subunit GluR1, and N-methyl-D-aspartate receptor subunit NR1, but not with the inhibitory synaptic markers vesicular gamma-aminobutyric acid (GABA) transporter (VGAT) and GABA(A) receptor subunit beta2 (GABA(A) beta2), which could reflect enhanced association of SC1 with excitatory synapses. These findings suggest that SC1 may be involved in synaptic modifications underlying epileptogenesis.
Lively
Starlee
S
Center for the Neurobiology of Stress, University of Toronto at Scarborough, Toronto, Ontario, Canada.
Brown
Ian R
IR
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D008094:Lithium / Q000633:toxicity; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D018721:Muscarinic Agonists / Q000633:toxicity; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism; D013226:Status Epilepticus / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D018721:Muscarinic Agonists; C503128:Sparcl1 protein, rat; D010862:Pilocarpine; D008094:Lithium