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*

Objective To summarize the experience of totally endoscopic thyroidectomy (TET) in treating differentiated thyroid carcinoma and to evaluate its feasibility, safety and the therapeutic result.Methods The clinical data of 25 cases of thyroid carcinoma treated with TET via the areola of breast or by axillary approach from November 2004 to July 2009 in our hospital were retrospectively analyzed.Result TET procedures were successfully performed in all 25 cases. Postoperative pathology confirmed that 23 cases were of papillary cancer and the other 2 were follicle cancer. Lobectomy and subtotal thyroidectomy were performed in 11and 14 cases respectively. In 7 cases additional lymph node dissection was performed.All the cases were followed-up, ranging from 5 to 58 months, with a median of 28 months. No recurrence was found during this period. There was no morbidity nor major complications and patients were all satisfied with the cosmetic effect. Conclusion Totally endoscopic thyroidectomy (TET) is curative, safe and cosmetic therapy for differentiated thyroid carcinoma.

In hippocampus, numerous studies have shown that N-methyl-D-aspartate (NMDA) receptors are essential for the initiation of long-term potentiation (LTP), whereas the expression of LTP is primarily mediated by the phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the increased insertion of postsynaptic AMPA receptors. However, in recent years there is also evidence that NMDA receptor channels contribute to the expression of LTP under physiological conditions. It was examined whether NMDA receptor channels contributed to the expression of LTP of C-fiber evoked field potentials in rat spinal dorsal horn by intravenous or spinal application of NMDA receptor antagonists after the establishment of LTP. It was found that MK 801 (a non-competitive NMDA receptor antagonist) at dose of 0.1 mg/kg (iv) had no effect on the spinal LTP and at the dose of 0.5 mg/kg depressed the LTP significantly. However, the inhibitory effect of MK 801 at higher dose (1.0 mg/kg)was not different from that produced by the dose of 0.5 mg/kg. The similar inhibitory effect on spinal LTP was also observed, when MK 801 was applied locally at the recording segments of spinal cord. To confirm the above results, a competitive NMDA receptor antagonist AP V was tested. Spinal application of AP V at a concentration of 100 μmol/L produced a stronger depression than at 50 μmol/L. When the concentration of AP V increased to 200 μmol/L, no further depression was observed. These results indicate that NMDA receptor channels are involved in the expression of LTP of C-fiber evoked field potentials in the rat spinal dorsal horn.