Cui Zhao1,2, Bo Zhou1, Junjie Cao2, Yafang Zhang3, Wei Li2, Miao Wang2, Xi Zhang1, Yiwei Wang2. 1. The Department of Neurology, the Second Medical Center, National Clinical Research Center for Geriatric Disease, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing. 2. Affiliated Hospital of Chengde Medical University, Chengde. 3. The Third People's Hospital of Heze City, Shandong Province, Heze, People's Republic of China.
Abstract
PURPOSE: When threatened, fear is one of the most important responses that an organism exhibits. The mechanisms involved in forming fear memories include specific neurological structures, neural circuits and detailed molecular interactions. METHODS: MicroRNAs (miRNAs, small non-coding RNAs) act as endogenous functional small molecules that participate in or interfere with the formation of new fear memory by inhibiting the expression of mRNA targets. MicroRNA-187 (miR-187) is a newly reported miRNA that is related to cancer, but it has not been investigated regarding fear memory formation. RESULTS: In the present study, we observed a transient reduction in the level of miR-187 in the dorsal hippocampus after a classic contextual fear conditioning (CFC) training. Overexpression of miR-187-3p in the DH using miR-187-3p agomir was detrimental in the formation of CFC memory, whereas downregulation of miR-187-3p using antagomir enhanced the formation of CFC memory. Additionally, utilization of bioinformatic methods and luciferase reporter assay revealed that miR-187-3p targets SATB2, and therefore miR-187-3p agomir can decrease the protein level of SATB2. Furthermore, we determined that SATB2 plays a role in the formation of CFC memory by miR-187-3p, which can be mediated by altering SATB2 expression. CONCLUSION: Altogether, evidence obtained from both in-vitro and in-vivo experiments indicated that miR-187-3p is involved in CFC memory formation through modulation of SATB2. Our data provides a basis for the potential therapeutic benefits of miR-187-3p/SATB2 in the treatment of anxiety disorders induced from fear memory.
PURPOSE: When threatened, fear is one of the most important responses that an organism exhibits. The mechanisms involved in forming fear memories include specific neurological structures, neural circuits and detailed molecular interactions. METHODS: MicroRNAs (miRNAs, small non-coding RNAs) act as endogenous functional small molecules that participate in or interfere with the formation of new fear memory by inhibiting the expression of mRNA targets. MicroRNA-187 (miR-187) is a newly reported miRNA that is related to cancer, but it has not been investigated regarding fear memory formation. RESULTS: In the present study, we observed a transient reduction in the level of miR-187 in the dorsal hippocampus after a classic contextual fear conditioning (CFC) training. Overexpression of miR-187-3p in the DH using miR-187-3p agomir was detrimental in the formation of CFC memory, whereas downregulation of miR-187-3p using antagomir enhanced the formation of CFC memory. Additionally, utilization of bioinformatic methods and luciferase reporter assay revealed that miR-187-3p targets SATB2, and therefore miR-187-3p agomir can decrease the protein level of SATB2. Furthermore, we determined that SATB2 plays a role in the formation of CFC memory by miR-187-3p, which can be mediated by altering SATB2 expression. CONCLUSION: Altogether, evidence obtained from both in-vitro and in-vivo experiments indicated that miR-187-3p is involved in CFC memory formation through modulation of SATB2. Our data provides a basis for the potential therapeutic benefits of miR-187-3p/SATB2 in the treatment of anxiety disorders induced from fear memory.