Modulation of ischemia-induced NMDAR1 activation by environmental enrichment decreases oxidative damage - PubMed (original) (raw)

Comparative Study

. 2011 Dec;28(12):2485-92.

doi: 10.1089/neu.2011.1842. Epub 2011 Aug 29.

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Comparative Study

Modulation of ischemia-induced NMDAR1 activation by environmental enrichment decreases oxidative damage

Teresita L Briones et al. J Neurotrauma. 2011 Dec.

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Abstract

In this study, we examined whether enriched environment (EE) housing has direct neuroprotective effects on oxidative damage following transient global cerebral ischemia. Fifty-two adult male Wistar rats were included in the study and received either ischemia or sham surgery. Once fully awake, rats in each group were randomly assigned to either: EE housing or socially paired housing (CON). Animals remained in their assigned environment for 7 days, and then were killed. Our data showed that glutamate receptor expression was significantly higher in the hippocampus of the ischemia CON group than in the ischemia EE group. Furthermore, the oxidative DNA damage, protein oxidation, and neurodegeneration in the hippocampus of the ischemia CON group were significantly increased compared to the ischemia EE group. These results suggest that EE housing possibly modulated the ischemia-induced glutamate excitotoxicity, which then attenuated the oxidative damage and neurodegeneration in the ischemia EE rats.

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Figures

FIG. 1.

FIG. 1.

Representative photomicrographs of Fluoro-Jade staining in the sham (left panel), ischemia CON (middle panel), and ischemia EE (right panel) animals. SO, stratum oriens; SP, stratum pyramidale; SR, stratum radiatum. Scale bar=100 μm.

FIG. 2.

FIG. 2.

Representative Western blot of sham (S) and ischemia (I) groups (upper panel). NMDAR1 levels significantly increased in the ischemic rats compared to the sham groups but housing rats in EE after injury attenuated that upregulation (A). Significant elevation in NMDAR1 activity was also seen after ischemic injury but modulated by EE housing (post-hoc comparison between ischemia EE and ischemia CON). Significant increase in NMDAR1 activity was also seen in the sham EE rats compared to the sham control animals (B). *p<0.05, **p<0.01. EE,enriched environment; CON, controls.

FIG. 3.

FIG. 3.

Representative photomicrographs of 8-OHdG immunostaining in the ischemic animals taken from the CA3 area where most of the immunoreactivities were observed (upper panel). Significantly increased oxidative DNA damage was seen in the ischemic rats compared to the sham groups (bar graph). However, post-hoc comparisons between the ischemia EE and ischemia CON groups showed that housing rats in the enriched environment after injury significantly attenuated oxidative damage to DNA. *p<0.05, **p<0.01. EE, enriched environment; CON, controls; Isch, ischemia. Scale bar=50 μm.

FIG. 4.

FIG. 4.

Representative oxyblot staining in the sham (S) and ischemia (I) groups (upper panel). Significantly increased protein carbonyl levels were seen in the ischemia group compared to shams. However, post-hoc comparisons between the ischemia EE and ischemia CON groups showed that housing rats in the enriched environment after ischemic injury resulted in a significant reduction in protein carbonylation. *p<0.05, **p<0.01. EE or E, enriched environment; CON or C, controls.

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