[PubMed] [Google Scholar]Zahrt J, Taylor JR, Mathew RG, Arnsten AF. that bilateral infusion of APV into the medial prefrontal cortex prior to testing significantly improved both sets of behaviors in gonadectomized rats and significantly worsened performance measures in gonadally intact controls. In hormone-replaced cohorts, we further found that behaviors that are normally similar to controls were significantly disrupted by APV, and those that are normally similar to gonadectomized rats were rescued by intracortical APV infusion. There were, however, no residual effects of APV on retention testing conducted 24 hours later. Together these findings suggest that hormone regulation of NMDAR-mediated activity specifically within the PFC may be fundamental to the effects of gonadal steroids on spatial cognition in males. Our findings further identify NMDAR antagonists as potentially novel, nonsteroidal means of attenuating the cognitive deficits that can accompany gonadal hormone decline in human males in aging, clinical cases of hypogonadalism and in certain neurologic and psychiatric illnesses. Accordingly, it may be important to obtain in males the kind of detailed knowledge concerning hormone effects on, for example, the channel and electrophysiological properties of NMDAR that currently exists for the female brain. < 0.05 was accepted as significant. The comparative data from non-infused subjects (CTRL, n=7; GDX n=8; GDX-E, n=7; GDX-TP, n=8) were obtained from a separate study in which testing took place 4C6 months prior to testing of the infusion groups (Locklear and Kritzer, 2014). 2.0 RESULTS 2.1 Effectiveness of Hormone Treatments The weights of the androgen sensitive bulbospongiosus muscles (BSM) showed group differences that paralleled expected differences in circulating androgen levels. Thus, muscle weights of the APV and saline infused CTRL rats (CTRL-apv, CTRL-s) were on Pirinixil average 1.78g and 1.77g, respectively, and those of the APV and saline infused GDX-TP groups (GDX-TP-apv, GDX-TP-s) were on average 1.64g and 1.66g, respectively (Fig 2). In contrast, in both the APV and saline infused GDX and GDX-E groups, average BSM weights were between 0.33g and 0.46g (Fig 2). Statistical comparisons of individual rats muscle weights (one-way ANOVA) confirmed that there were significant main effects of Group [< 0.001] on muscle mass. The allowed post hoc comparisons further showed that BSM weights of saline and APV-infused CTRL and GDX-TP rats were all similar to each other; that the BSM weights of saline- and APV-infused GDX and GDX-E rats were all similar to each other; and that mean muscle weights of both the saline- and APV-infused CTRL and GDX-TP groups were significantly larger than those of both the saline- and APV-infused GDX and GDX-E groups (< 0.001, Fig 2). Open in a separate window Figure 2 Bar graphs showing group average bulbospongiosus muscle weights in grams (g) plus standard errors of the mean for rat groups that were infused with saline (black bars) or with APV (gray bars) prior to Barnes maze testing. The mean weights from gonadally intact control (CTRL-S, CTRL-APV), gonadectomized (GDX-S, GDX-APV), and gonadectomized male rats supplemented with testosterone propionate (GDX-TP-S, GDX-TP-APV) or estradiol (GDX-E-S, GDX-E-APV) are shown. Muscle weights of the two CTRL and GDX-TP groups were similar to each other and were significantly greater than those of the two GDX and GDX-E groups. Muscle weights of the two GDX and GDX-E groups were also similar to each other. Asterisks denote significant differences from CTRL-S for post-hoc testing at the < 0.05 level. 2.2 Barnes Maze Testing: Path Lengths, Errors and Latencies to Goal Previous studies have shown that during Day 1 testing, GDX rats follow significantly longer routes, make significantly more errors (primary and secondary) and take significantly longer to locate the goal than CTRL, GDX CE or GDX-TP rats (Locklear and Kritzer, 2014). Saline vehicle injections prior to testing had no effect on these group differences (Figs 3C5, left panels). Thus, at the conclusion of Day 1 testing, in comparison to saline-infused CTRL, GDX-E and GDX-TP Pirinixil groups the GDX-s cohort followed longer average path Mouse monoclonal to HSP60 lengths (GDX-s ? 300cm; CTRL-s, GDX-E-s ? 120 cm; GDX-TP-s ? 240 cm, Fig 3A), committed higher mean numbers of errors (primary errors: GSX-s ? 8 errors, CTRL-s, GDX-E-s, GDX-TP-s ? 3C4 errors, Fig 4C: secondary errors: GSX-s ? 3 errors, CTRL-s, GDX-E-s, GDX-TP-s ? 0C1 error, Fig. 4C) and had longer mean latencies in locating the goal (GSX-s ? 70 seconds, CTRL-s, GDX-E-s, GDX-TP-s ? 30C40 seconds, Fig 5A). Analyses of variance (two-way, repeated measures) identified significant main effects of Group for path Pirinixil length (F3,13 = 3.77, p=0.038), primary errors (F3,13 = 10.35, p<0.001) and latency to goal (F3,13 = 4.14, p=0.029) and significant main effects of Trial for path length (F3,39 = 6.74, p=0.001), secondary errors (F3,39 = 9.96, p<0.001) and latency to goal (F2.03,26.44 = 5.69, p=0.009). Interactions between Group and Trial were not significant for any outcome measure. Allowed post.
[PubMed] [Google Scholar]Zahrt J, Taylor JR, Mathew RG, Arnsten AF
Previous articleIn the NCI-H727 line, all molecular markers were strongly portrayed except MGMT (score of 2)Next article 2combination outcomes using BMS-536924 merging with the pan-HER inhibitor BMS-690514(33) or an EGFR inhibitor gefitinib; synergistic or additive antiproliferative results (Supplementary Fig