Neuropathic pain is frequently comorbidity with cognitive deficits. Neuralized1 (Neurl1)-mediated ubiquitination of CPEB3 in the hippocampus is critical in learning and memory. However, the role of Neurl1 in the cognitive impairment in neuropathic pain remains elusive. Herein, we found that lumbar 5 spinal nerve ligation (SNL) in male rat-induced neuropathic pain was followed by learning and memory deficits and LTP impairment in the hippocampus. The Neurl1 expression in the hippocampal CA1 was decreased after SNL. And this decrease paralleled the reduction of ubiquitinated-CPEB3 level and reduced production of GluA1 and GluA2. Overexpression of Neurl1 in the CA1 rescued cognitive deficits and LTP impairment, and reversed the reduction of ubiquitinated-CPEB3 level and the decrease of GluA1 and GluA2 production following SNL. Specific knockdown of Neurl1 or CPEB3 in bilateral hippocampal CA1 in naïve rats resulted in cognitive deficits and impairment of synaptic plasticity. The rescued cognitive function and synaptic plasticity by the treatment of overexpression of Neurl1 before SNL were counteracted by the knockdown of CPEB3 in the CA1. Collectively, the above results suggest that the downregulation of Neurl1 through reducing CPEB3 ubiquitination and, in turn, repressing GluA1 and GluA2 production and mediating synaptic plasticity impairment in hippocampal CA1 leads to the genesis of cognitive deficits in neuropathic pain.
Animals ; Male ; Neuralgia/metabolism* ; Rats ; Down-Regulation/physiology* ; Ubiquitination/physiology* ; Neuronal Plasticity/physiology* ; Rats, Sprague-Dawley ; CA1 Region, Hippocampal/metabolism* ; Cognitive Dysfunction/metabolism* ; RNA-Binding Proteins/metabolism* ; Receptors, AMPA/metabolism*

AIM: To explore the effect of L-arginine (L-Arg) on the arrhythmia induced by ischemia/reperfusion (IR) of the right coronary artery in rabbits. METHODS: 48 healthy adult rabbits were divided into 4 groups (n=12 of each) randomly: IRa group (120 min reperfusion after 30 min ischemia), IRb group (120 min reperfusion after 120 min ischemia), IRa+L-Arg group and IRb+L-Arg group. I/R model was established by occluding and loosening the root of the right coronary artery in rabbits. The changes of ECG and arrhythmia were recorded and graded. RESULTS: ① The longer time of IR was, the higher the score of the arrhythmia was found. The incidence of atrial-ventricular block (AVB), sinus-atrial block (SAB), even sinus arrest were detected and aggravated gradually. ② The incidence of AVB was decreased and from Ⅲ?→Ⅱ?→Ⅰ? markedly, some of sinus and atrial arrhythmia were transformed into sinus rhythm gradually, and all of the arrhythmia scores in IRa group were decreased significantly as compared with the same time phases of IRb group (P