Cellular neuroscienceKnockout of the mu opioid receptor enhances the survival of adult-generated hippocampal granule cell neurons
Section snippets
Animals
Adult male mice with a deletion of exon 1 of MOR were created on a C57BL/6 and 129Sv mixed background as previously described (Sora et al., 1997). MOR KO mice were generated from heterozygote crosses to produce wild-type (WT), heterozygote, and homozygote littermates. WT, heterozygote KO and homozygote KO mice were genotyped by polymerase chain reaction (PCR) using two internal primers, one targeted at the NEO insertion in the KO construct and one targeted at the WT gene, and one external
Proliferation
Two hours after BrdU injection, BrdU-IR cells were evident in the SGZ and GCL of the hippocampus. As previously shown, proliferating cells were small, clustered, and irregularly shaped (Fig. 1). No differences were evident in the size, clustering, or shape of BrdU-IR cells across genotypes. Quantification of the total number of BrdU-IR cells showed no significant effect of genotype in the GCL (Fig. 1B; F(2,19)=1.430, P>0.05) or the habenula (Fig. 1B; F(2,19)=0.478, P>0.05), a region we use to
Discussion
These data show that heterozygote and homozygote MOR KO mice have enhanced adult hippocampal neurogenesis. This effect is due to an increase in the number of progenitor cells that survive, not to alteration in the number of proliferating GCL cells, and is independent of detectable changes in cell death. There is no influence of the MOR KO on cell fate determination since WT, heterozygote and homozygote mice all had equivalent proportions of surviving cells maturing into neurons. The impact of
Conclusion
In summary, these findings implicate MOR as necessary for the survival of newly mature neurons in the hippocampus. We extrapolate that endogenous opioids may act to regulate numbers of surviving newly born neurons by binding to MOR to cause this suppression. Thus, opioids and opiates have the potential to negatively impact hippocampal-dependent learning and memory by decreasing neurogenesis.
Acknowledgments
Funding for this research was generously provided by NIH/NIDA R01 DA016765 (A.J.E.), NIDA T32 DA007290 (G.C.H.), and the NIDA Intramural Research Program (F.S.H. and G.R.U.).
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