Down-regulation of Stargazin Inhibits the Enhanced Surface Delivery of α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionate Receptor GluR1 Subunit in Rat Dorsal Horn and Ameliorates Postoperative Pain

Stargazin is the first transmembrane protein known to regulate synaptic targeting of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Yet, it is unclear whether regulation of the surface delivery of spinal AMPA receptor subunits by stargazin contributes to postoperative pain development

miRNA expression profile and involvement of Let-7d-APP in aged rats with isoflurane-induced learning and memory impairment.

MicroRNAs (miRNAs) play a key role in different nervous system diseases. We sought to determine the role of miRNAs in isoflurane-induced learning and memory impairment in aged rats. Male Sprague-Dawley (SD) rats of 18 month were randomly assigned to control group (exposed to mock anesthesia), 2-hour group and 6-hour group (exposed to 2% isoflurane for 2 and 6 hours respectively). By Morris Water Maze, 6-hour group showed impaired learning and memory ability while 2-hour group not. As shown by miRNA array, control group and 2-hour group showed a similar miRNA expression profile. And 38 miRNAs are differently expressed in 6-hour group compared to the other 2 groups, including 21 up-regulated miRNAs and 17 down-regulated miRNAs. And 4 of the differentially expressed miRNAs were validated independently by qRT-PCR. Let-7d was downregulated in 6-hour group. Additionally, we demonstrated that amyloid precursor protein (APP) was a direct target of let-7d by Fluorescent report assay. Increased expression of APP and amyloid-β (Aβ) were found in the hippocampi of 6-hour group. Downregulation of let-7d might contribute to isoflurane-induced learning and memory impairment through upregulating its target APP, and increasing the production of Aβ subsequently

Down-regulation of Stargazin Inhibits the Enhanced Surface Delivery of α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionate Receptor GluR1 Subunit in Rat Dorsal Horn and Ameliorates Postoperative Pain

Stargazin is the first transmembrane protein known to regulate synaptic targeting of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Yet, it is unclear whether regulation of the surface delivery of spinal AMPA receptor subunits by stargazin contributes to postoperative pain development

Heat map of microRNA microarray expression data from hippocampus samples of 3 groups.

<p>The expression of miRNAs is hierarchically clustered on the y axis, and hippocampus samples of 3 groups are hierarchically clustered on the x axis. Number with C represent control group, number with 2h represent 2-hour group, number with 6h means 6-hour group. The legend on the right indicates the miRNA represented in the corresponding row. The color scale on the right show the relative miRNA expression, green means downregulation, while red means upregulation, n = 4 per group.</p

Sequences of the primers used in the SYBR-green-based quantitative RT-PCR validation.

<p>Sequences of the primers used in the SYBR-green-based quantitative RT-PCR validation.</p

Learning and memory testing of 3 groups before and after anesthesia.

<p><b>A</b>, The time to reach the platform (Escape latency period, ELP) for 3 groups before anesthesia (Reference memory testing). No difference was found among groups in the reference memory testing before anesthesia exposure. <b>B</b>, Escape latency period of 3 groups after anesthesia (Reversal Testing). After exposure to the isoflurane or mocked anesthesia, 6-hour group took longer to reach the platform during the reversal testing than the other 2 groups, while escape latencies of 2-hour group were not longer than contol group. *p<0.05 vs. control, <b>#</b>p<0.05 vs. 2-hour group, n = 16 per group.</p

Differentially expressed miRNAs in 6-hour group compared with the other 2 groups.

<p>Differentially expressed miRNAs in 6-hour group compared with the other 2 groups.</p