5-HT_2C serotonin receptor blockade prevents tau protein hyperphosphorylation and corrects the defect in hippocampal synaptic plasticity caused by a combination of environmental stressors in mice

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• 作者：Carla Letizia Busceti^a ; ^{carla.busceti@neuromed.it" class="auth_mail" title="E-mail the corresponding author} ; Paola Di Pietro^a ; ^{p.dipietro06@virgilio.it" class="auth_mail" title="E-mail the corresponding author} ; Barbara Riozzi^a ; ^{barbara.riozzi@neuromed.it" class="auth_mail" title="E-mail the corresponding author} ; Anna Traficante^a ; ^{annatraficante@yahoo.it" class="auth_mail" title="E-mail the corresponding author} ; Francesca Biagioni^a ; ^{frbiagioni@libero.it" class="auth_mail" title="E-mail the corresponding author} ; Robert Nistic&ograve ; ^b ; ^c ; ^{robert.nistico@gmail.com" class="auth_mail" title="E-mail the corresponding author} ; Francesco Fornai^a ; ^d ; ^{francesco.fornai@med.unipi.it" class="auth_mail" title="E-mail the corresponding author} ; Giuseppe Battaglia^a ; ^{giuseppe.battaglia@neuromed.it" class="auth_mail" title="E-mail the corresponding author} ; Ferdinando Nicoletti^a ; ^b ; ^{ferdinandonicoletti@hotmail.com" class="auth_mail" title="E-mail the corresponding author} ; Valeria Bruno^a ; ^b ; ^{valeria.bruno@uniroma1.it" class="auth_mail" title="E-mail the corresponding author}
• 关键词：EDTA ; ethylenediaminetetraacetic acid ; fEPSPs ; field excitatory postsynaptic potentials ; GSK-3尾 ; glycogen synthase kinase-3尾 ; FJB ; fluoro-jade B ; GFAP ; glial fibrillary acidic protein ; HFS ; high frequency stimulation ; 5-HIAA ; 5-hydroxyindoloacetic acid ; HPLC ; high-performance liquid chromatography ; 5-HT ; serotonin ; LTP ; long-term potentiation ; MDMA ; 3 ; 4-methylendioxymethamphetamine ; PFA ; paraformaldehyde ; PPF ; paired-pulse facilitation ; PVDF ; polyvinylidene difluoride ; RAWM ; radial arm water maz
• 刊名：Pharmacological Research
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：99
• 期：Complete
• 页码：258-268
• 全文大小：3968 K

文摘

Exposure to multimodal sensory stressors is an everyday occurrence and sometimes becomes very intense, such as during rave parties or other recreational events. A growing body of evidence suggests that strong environmental stressors might cause neuronal dysfunction on their own in addition to their synergistic action with illicit drugs. Mice were exposed to a combination of physical and sensory stressors that are reminiscent of those encountered in a rave party. However, this is not a model of rave because it lacks the rewarding properties of rave. A 14-h exposure to environmental stressors caused an impairment of hippocampal long-term potentiation (LTP) and spatial memory, and an enhanced phosphorylation of tau protein in the CA1 and CA3 regions. These effects were transient and critically depended on the activation of 5-HT_2C serotonin receptors, which are highly expressed in the CA1 region. Acute systemic injection of the selective 5-HT_2C antagonist, RS-102,221 (2 mg/kg, i.p., 2 min prior the onset of stress), prevented tau hyperphosphorylation and also corrected the defects in hippocampal LTP and spatial memory. These findings suggest that passive exposure to a combination of physical and sensory stressors causes a reversible hippocampal dysfunction, which might compromise mechanisms of synaptic plasticity and spatial memory for a few days. Drugs that block 5-HT_2C receptors might protect the hippocampus against the detrimental effect of environmental stressors.