Environmental enrichment alters nerve growth factor-induced gene A and glucocorticoid receptor messenger RNA expression after middle cerebral artery occlusion in rats
Section snippets
Surgery and housing
The experimental protocol was approved by the Ethics Committee for Animal Research at Lund University. All efforts were made to minimize animal discomfort and to reduce the number of animals used. No alternative in vitro techniques were considered adequate for these studies. The data in this work were collected from two separate experiments: (i) two to 12 days after middle cerebral artery (MCA) occlusion and (ii) 20–30 days after brain ischemia. The two experiments were carried out identically:
Infarct volume
The cortical infarct volume did not differ significantly between rats housed in the standard and the enriched environments at any time-point after MCA occlusion (Table 1).
Nerve growth factor-induced gene A messenger RNA expression in the cerebral cortex
NGFI-A was expressed throughout the cerebral cortex outside the infarct, with the highest expression in layers IV and VI (Fig. 1). Two and three days after MCA occlusion, NGFI-A mRNA expression in cortical regions outside the lesion was decreased (44–91%) in rats from both environmental conditions (Fig. 1, Fig. 2). This
Discussion
The major findings of this study are: (i) dynamic changes in NGFI-A mRNA expression two to 30 days after MCA occlusion in brain regions remote from the ischemic lesion, effects profoundly influenced by environmental enrichment; (ii) a decrease in hippocampal GR mRNA levels in standard housed rats that could be counteracted by environmental enrichment. Importantly, these effects were unrelated to cortical infarction volumes, which did not differ significantly between groups.
Two and three days
Conclusion
We have found that NGFI-A and GR mRNA expression after focal cerebral ischemia is significantly influenced by environmental enrichment in spontaneously hypertensive rats. Altered expression of specific transcription factors, in brain areas remote from the primary lesions, may be involved in the improved outcome induced by environmental enrichment after focal cerebral ischemia.
Acknowledgments
We thank Prof. J. Milbrandt, Prof. R. Miesfeld and Prof. J. Arriza for kindly providing us with the NGFI-A, GR and MR cDNA clones, respectively. We also thank Mikaela Háková and Else-Britt Lundström for excellent technical assistance. This study was supported by grants from the Swedish Medical Research Council [projects 14X-12237, 19P-11769 (T.O.) and 14X-4968 (B.B.J.)], Västerbotten County Council, the Söderberg Foundation, the Swedish Society for Medicine, Ostermans Research Funds, the Magnus
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