Please use this identifier to cite or link to this item:
http://hdl.handle.net/10397/66464
| Title: | Impaired bidirectional NMDA receptor dependent synaptic plasticity in the dentate gyrus of adult female Fmrl heterozygous knockout mice | Authors: | Yau, SY Bostrom, CA Chiu, J Fontaine, CJ Sawchuk, S Meconi, A Wortman, RC Truesdell, E Truesdell, A Chiu, C Hryciw, BN Eadie, BD Ghilan, M Christie, BR |
Issue Date: | Dec-2016 | Source: | Neurobiology of disease, Dec. 2016, v. 96, p. 261-270 | Abstract: | Fragile-X syndrome (FXS) is caused by the transcriptional repression of the Fmrl gene resulting in loss of the Fragile-X mental retardation protein (FMRP). This leads to cognitive impairment in both male and female patients, however few studies have focused on the impact of FXS in females. Significant cognitive impairment has been reported in approximately 35% of women who exhibit a heterozygous Fmrl gene mutation, however to date there is a paucity of information regarding the mechanistic underpinnings of these deficits. We, and others, have recently reported that there is significant impairment in N-methyl-D-aspartate receptor (NMDAR)-dependent long-term potentiation (LTP) and long-term depression (LTD) in the hippocampal dentate gyrus (DG) of male Fmrl knock out mice. Here we examined if female mice displaying a heterozygous loss of the Fmrl gene (Fmr1(+/-)) would exhibit similar impairments in DG-dependent spatial memory processing and NMDAR hypofunction. We found that Female Fmr1(+/-) mice did not show impaired metabotropic glutamate receptor (mGluR)-LTD in the CA1 region, and could perform well on a temporal ordering task that is thought to involve this brain region. In contrast, female Fmr1+/- mice showed impairments in a pattern separation task thought to involve the DG, and also displayed a significant impairment in both NMDAR-dependent LTD and LTP in this region. The LTP impairment could be rescued by administering the NMDAR co-agonist, glycine. Our data suggests that NMDAR hypofunction in the DG may partly contribute to learning and memory impairment in female Fmr1(+/-) mice. Targeting NMDAR-dependent mechanisms may offer hope as a new therapeutic approach for treating female FXS patients with learning and memory impairments. | Keywords: | Fragile X syndrome Females Hippocampus Learning and memory Synaptic plasticity |
Publisher: | Academic Press | Journal: | Neurobiology of disease | ISSN: | 0969-9961 | EISSN: | 1095-953X | DOI: | 10.1016/j.nbd.2016.09.012 | Rights: | © 2016 Elsevier Inc. All rights reserved. © 2016. This manuscript version is made available under the CC-BY-NC-ND 4.0 license https://creativecommons.org/licenses/by-nc-nd/4.0/ The following publication Yau, S. Y., Bostrom, C. A., Chiu, J., Fontaine, C. J., Sawchuk, S., Meconi, A., ... & Christie, B. R. (2016). Impaired bidirectional NMDA receptor dependent synaptic plasticity in the dentate gyrus of adult female Fmr1 heterozygous knockout mice. Neurobiology of disease, 96, 261-270 is available at https://doi.org/10.1016/j.nbd.2016.09.012. |
| Appears in Collections: | Journal/Magazine Article |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| Yau_Impaired_Bidirectional_Nmda.pdf | Pre-Published version | 801.63 kB | Adobe PDF | View/Open |
Access
View full-text via PolyU eLinks 
Page views
39
Last Week
0
0
Last month
Citations as of Oct 1, 2023
Downloads
48
Citations as of Oct 1, 2023
SCOPUSTM
Citations
15
Last Week
0
0
Last month
Citations as of Sep 28, 2023
WEB OF SCIENCETM
Citations
16
Last Week
0
0
Last month
Citations as of Sep 28, 2023
Google ScholarTM
Check
Altmetric
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.