Neural (N-) cadherin, a synaptic adhesion molecule, is induced in hippocampal mossy fiber axonal sprouts by seizure.
Aberrant mossy fiber sprouting and synaptic reorganization are plastic responses in human temporal lobe epilepsy, and in pilocarpine-induced epilepsy in rodents. Although the morphological features of the hippocampal epileptic reaction have been well documented, the molecular mechanisms underlying these structural changes are not understood. The classic cadherins, calcium-dependent cell adhesion molecules, are known to function in development in neurite outgrowth, synapse formation, and stabilization. In pilocarpine-induced status epilepticus, the expression of N-cadherin mRNA was sharply upregulated and reached a maximum level (1- to 2.5-fold) at 1- to 4 weeks postseizure in the granule cell layer and the pyramidal cell layer of CA3. N-cadherin protein was correspondingly increased and became concentrated in the inner molecular layer of the dentate gyrus, consistent with the position of mossy fiber axonal sprouts. Moreover, N-cadherin labeling was punctate; colocalized with definitive synaptic markers, and partially localized on polysialated forms of neural cell adhesion molecule (PSA-NCAM)-positive dendrites of granule cells in the inner molecular layer. Our findings show that N-cadherin is likely to be a key factor in responsive synaptogenesis following status epilepticus, where it functions as a mediator of de novo synapse formation.
Shan
Weisong
W
The Corinne Goldsmith Dickinson Center for Multiple Sclerosis, The Mount Sinai School of Medicine, New York, New York 10029, USA. Weisong.shan@mssm.edu
Yoshida
Mika
M
Wu
Xi-Ru
XR
Huntley
George W
GW
Colman
David R
DR
D000818:Animals; D001369:Axons / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D015151:Immunoblotting; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000378:metabolism*; D018721:Muscarinic Agonists / Q000494:pharmacology; D010862:Pilocarpine / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects
D015820:Cadherins; D018721:Muscarinic Agonists; D012333:RNA, Messenger; D010862:Pilocarpine