Distinct function of miR-17-92 cluster in the dorsal and ventral adult hippocampal neurogenesis

https://doi.org/10.1016/j.bbrc.2018.07.086Get rights and content

Highlights

  • miR-17-92 is highly related with hippocampal neurogenesis and mood behavior.

  • The expression of miR-17-92 cluster is regionally different in hippocampus.

  • miR-17-92 KO less affect development of neural progenitors in ventral hippocampus.

  • Interestingly, memory function was not altered by miR-17-92 KO.

  • These findings suggest the distinct function of regional expression of miR-17-92.

Abstract

It has been known that the dorsal and ventral areas of the dentate gyrus in the hippocampus have distinct roles in memory and mood behaviors. We previously reported that microRNA miR-17-92 regulates adult hippocampal neurogenesis and mood disorders. Here, we suggest that the miR-17-92 cluster is highly expressed in the ventral than the dorsal dentate gyrus in the adult mouse hippocampus. Deletion of miR-17-92 in the adult hippocampus only affects development of neural progenitors in the ventral dentate gyrus, and miR-17-92 knockout mice have no defects in memory functions. Our results suggest that regional expression of miR-17-92 in the dentate gyrus is associated with their distinct functions in hippocampal neurogenesis and related behaviors.

Introduction

MicroRNAs (miRNAs) are known to be involved in the pathogenesis of neurological disorders [[1], [2], [3], [4]], although the molecular mechanisms are not well understood. Previous studies have shown that miR-135 and miR-16 play a role in targeting the serotonin transporter [5,6], and miR-18 might affect the glucocorticoid pathway [7,8] in the brain. Moreover, it has been reported that miR-17-92 cluster has function not only in neural development [9,10] but also in the recovery of ischemic brain [11,12].

The dentate gyrus of the mammalian hippocampus is populated by neural stem cells and neural progenitors, which maintain generation of new neurons [13]. These new neurons integrate into the neural network and might contribute to learning and memory during maturation phase. Adult hippocampal neurogenesis has been known to be related to anxiety, depression, and memory function [14]. Previously, we found that changes in miR-17-92 cluster affected anxiety- and depression-related behaviors by targeting stress-related gene, Sgk1 [15].

In recent studies, it has been reported that the hippocampal function is regionally distinct [14,16,17]. Among the studies, one study showed that the ventral hippocampus is more related to the mood disorder whereas the dorsal hippocampus closely linked to memory [14]. Here, we found that miR-17-92 displayed relatively higher expression in the ventral dentate gyrus of adult mouse hippocampus compared to the dorsal area. Interestingly, miR-17-92 knockout mice showed no significant changes in memory behaviors. Our study suggests that distinct roles of the miR-17-92 cluster on adult hippocampal neurogenesis and memory and mood behaviors are associated with their different expression in the ventral/dorsal areas in the hippocampus.

Section snippets

Animals

All animals used in this study were maintained at the facility of Weill Cornell Medical College, overseen by the Animal Facility, and approved by the Institutional Animal Care and Use Committee (IACUC). Experimental procedure was also approved by The Rockefeller University Institutional Animal Care and Use Committee. They were housed in normal cage at an environmental temperature, humidity, and under 12/12 h light/dark light cycle with food and water ad libitum. All experiments using animals

Results

In previous study, we found that miR-17-92 is highly expressed in the adult mouse hippocampus, especially in the dentate gyrus [15]. To determine whether miR-17-92 expression differ by region, we performed detailed analysis of miR-17-92 expressions on serial sections from the septal (dorsal) to temporal (ventral) hippocampus in the adult mouse using in situ hybridization. The dorsal part of the dentate gyrus showed lower expression, compared to the ventral part, as detected by probes for miR-17

Discussion

In this study, we have found that expression of the miR-17-92 cluster displays difference in distinct hippocampal regions. Regional difference of miRNA expression has been reported in various species and tissues [17,[22], [23], [24], [25]]. Distinct regions of the adult rat brain display different profiling of miRNA expression [23]. miRNA profiles of neural progenitors from different regions of the human brain also show region-specific expression patterns [22]. However, there is no study of

Role of authors

J.J. and S.-N.K. performed the research, J.J., H.K., T.S. and S-N.K. analyzed the data, H.K., T.S. and S.-N.K. wrote the paper.

Acknowledgements

This work was supported by an award from the Hirschl/Weill-Caulier Trust (T. S.), an R01-MH083680 grant from the NIH/NIMH (T. S.), the National Natural Science Foundation of China (81471152, 31771141 and 81701132) (T. S.) and National Research Foundation of Korea funded by the Korea government (MSIT) (NRF-2017R1C1B5018061) (S.-N. K.).

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