title: NMDA receptor triggered molecular cascade underlies compression-induced rapid dendritic spine plasticity in cortical neurons.
abstract: Compression causes the reduction of dendritic spines of underlying adult cortical pyramidal neurons but the mechanisms remain at large. Using a rat epidural cerebral compression model, dendritic spines on the more superficial-lying layer III pyramidal neurons were found quickly reduced in 12h, while those on the deep-located layer V pyramidal neurons were reduced slightly later, starting 1day following compression. No change in the synaptic vesicle markers synaptophysin and vesicular glutamate transporter 1 suggest no change in afferents. Postsynaptically, N-methyl-d-aspartate (NMDA) receptor trafficking to synaptic membrane was detected in 10min and lasting to 1day after compression. Translocation of calcineurin to synapses and enhancement of its enzymatic activity were detected within 10min as well. These suggest that compression rapidly activated NMDA receptors to increase postsynaptic calcium, which then activated the phosphatase calcineurin. In line with this, dephosphorylation and activation of the actin severing protein cofilin, and the consequent depolymerization of actin were all identified in the compressed cortex within matching time frames. Antagonizing NMDA receptors with MK801 before compression prevented this cascade of events, including NR1 mobilization, calcineurin activation and actin depolymerization, in the affected cortex. Morphologically, MK801 pretreatment prevented the loss of dendritic spines on the compressed cortical pyramidal neurons as well. In short, we demonstrated, for the first time, mechanisms underlying the rapid compression-induced cortical neuronal dendritic spine plasticity. In addition, the mechanical force of compression appears to activate NMDA receptors to initiate a rapid postsynaptic molecular cascade to trim dendritic spines on the compressed cortical pyramidal neurons within half a day.
authors.affiliation: Department of Anatomy, College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Li-Jin
authors.initials: LJ
authors.lastname: Chen
authors.affiliation: Department of Anatomy, College of Medicine, Tzu-Chi University, Hualien, Taiwan.
authors.forename: Yueh-Jan
authors.initials: YJ
authors.lastname: Wang
authors.affiliation: Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung, Taiwan.
authors.forename: Jeng-Rung
authors.initials: JR
authors.lastname: Chen
authors.affiliation: Department of Anatomy, College of Medicine, Tzu-Chi University, Hualien, Taiwan. Electronic address: guofang@mail.tcu.edu.tw.
authors.forename: Guo-Fang
authors.initials: GF
authors.lastname: Tseng
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D049229:Dendritic Spines / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D009408:Nerve Compression Syndromes / Q000378:metabolism*; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000473:pathology; D017966:Pyramidal Cells / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D018691:Excitatory Amino Acid Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C473649:NR1A NMDA receptor, rat; D016194:Receptors, N-Methyl-D-Aspartate; D002118:Calcium
keywords: Cerebral compression; Dendritic spine; NMDA receptor; Trauma