journal article·2025-03Open access

GABAergic Progenitor Cell Graft Rescues Cognitive Deficits in Fragile X Syndrome Mice

Chen Wang, Jia‐Yu Liu, Li‐Da Su, Xin‐Tai Wang, Yu‐Peng Bian, Zhao‐Xiang Wang, Lu‐Yu Ye, Xin‐Jiang Lu, Lin Zhou, Wei Chen, Wei Yang, Jun Liu, Luxi Wang, Ying Shen

Advanced Science· Volume 12· Issue 10

Abstract

Abstract Fragile X syndrome (FXS) is an inherited neurodevelopmental disorder characterized by a range of clinical manifestations with no effective treatment strategy to date. Here, transplantation of GABAergic precursor cells from the medial ganglionic eminence (MGE) is demonstrated to significantly improve cognitive performance in Fmr1 knockout (KO) mice. Within the hippocampus of Fmr1‐KO mice, MGE‐derived cells from wild‐type donor mice survive, migrate, differentiate into functionally mature interneurons, and form inhibitory synaptic connections with host pyramidal neurons. MGE cell transplantation restores Ras‐PKB signaling in pyramidal neurons, enhances AMPA receptor trafficking, rescues synaptic plasticity, and corrects abnormal hippocampal neural oscillations. These findings highlight the potential of GABAergic precursor cell transplantation as a promising therapeutic strategy for FXS.
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Research context

OpenAlex topics: Genetics and Neurodevelopmental Disorders · Autism Spectrum Disorder Research · Neurogenesis and neuroplasticity mechanisms

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Neurology Institute of Neuroscience Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China The Second Affiliated Hospital Guangzhou Medical University Guangzhou 510260 China

Department of Physiology and Department of Psychiatry Sir Run Run Shaw Hospital Zhejiang University School of Medicine Hangzhou 310058 China

Zhejiang Development & Planning Institute Hangzhou 310030 China

Neuroscience Care Unit Key Laboratory of Multiple Organ Failure of Ministry of Education the Second Affiliated Hospital of Zhejiang University School of Medicine Hangzhou 310009 China

Key Laboratory of the Diagnosis and Treatment of Severe Trauma and Burn of Zhejiang Province Hangzhou 310009 China

Institute of Life Sciences College of Life and Environmental Sciences Hangzhou Normal University Hangzhou 311121 China

Center for Brain Health the Fourth Affiliated Hospital of School of Medicine and International School of Medicine International Institutes of Medicine Zhejiang University Yiwu 322000 China

Zhejiang Lab Hangzhou 311500 China

Department of Biophysics Zhejiang University School of Medicine Hangzhou 310058 China

Department of Physiology Zhejiang University School of Medicine Hangzhou 310058 China

Key Laboratory for Precision Diagnosis Treatment and Clinical Translation of Rare Diseases of Zhejiang Province Zhejiang University School of Medicine Hangzhou 310058 China

Funding

National Natural Science Foundation of China · Natural Science Foundation of Zhejiang Province · Ministry of Science and Technology of the People's Republic of China

References (82)

Show source-provided references
1. 10.1002/dneu.2209610.1002/dneu.22096 ↗
2. 10.1126/science.769260110.1126/science.7692601 ↗
3. 10.1016/j.gene.2007.02.02610.1016/j.gene.2007.02.026 ↗
4. 10.1073/pnas.12220569910.1073/pnas.122205699 ↗
5. 10.1006/mcne.2001.108510.1006/mcne.2001.1085 ↗
6. 10.1016/j.cell.2006.09.01410.1016/j.cell.2006.09.014 ↗
7. 10.1186/1756-6606-6-1510.1186/1756-6606-6-15 ↗
8. 10.1016/j.neuron.2015.06.01710.1016/j.neuron.2015.06.017 ↗
9. 10.1146/annurev-pathol-011811-13245710.1146/annurev-pathol-011811-132457 ↗
10. 10.1038/nrn400110.1038/nrn4001 ↗
11. 10.1113/jphysiol.2008.15072210.1113/jphysiol.2008.150722 ↗
12. 10.1016/j.tins.2004.04.00910.1016/j.tins.2004.04.009 ↗
13. Berry‐Kravis E. M. · Nat. Rev. Drug. Discov. · 2017 · 4 · 280
14. 10.1161/CIRCRESAHA.111.25614910.1161/CIRCRESAHA.111.256149 ↗
15. 10.1126/science.124062210.1126/science.1240622 ↗
16. 10.1523/JNEUROSCI.1540-06.200610.1523/JNEUROSCI.1540-06.2006 ↗
17. 10.1073/pnas.090014110610.1073/pnas.0900141106 ↗
18. 10.1038/nature1152310.1038/nature11523 ↗
19. 10.1038/nn.339210.1038/nn.3392 ↗
20. 10.1523/JNEUROSCI.1714-10.201010.1523/JNEUROSCI.1714-10.2010 ↗
21. 10.4161/15384101.2014.98911410.4161/15384101.2014.989114 ↗
22. 10.1523/JNEUROSCI.2447-12.201310.1523/JNEUROSCI.2447-12.2013 ↗
23. 10.3389/fncel.2014.0024510.3389/fncel.2014.00245 ↗
24. 10.1038/nrn195410.1038/nrn1954 ↗
25. 10.1146/annurev-neuro-061010-11371710.1146/annurev-neuro-061010-113717 ↗
26. 10.1038/nrn.2017.4510.1038/nrn.2017.45 ↗
27. 10.1159/00036092510.1159/000360925 ↗
28. 10.1152/physrev.00007.201710.1152/physrev.00007.2017 ↗
29. 10.1371/journal.pone.018506710.1371/journal.pone.0185067 ↗
30. 10.1038/nm.233610.1038/nm.2336 ↗
31. 10.1038/nn.466110.1038/nn.4661 ↗
32. 10.1016/j.neubiorev.2016.06.03310.1016/j.neubiorev.2016.06.033 ↗
33. 10.1152/physrev.00018.201510.1152/physrev.00018.2015 ↗
34. 10.1037/0735-7044.122.2.48310.1037/0735-7044.122.2.483 ↗
35. 10.1016/j.neuron.2018.10.01810.1016/j.neuron.2018.10.018 ↗
36. 10.1016/S0896-6273(03)00722-010.1016/S0896-6273(03)00722-0 ↗
37. 10.1101/gad.34220510.1101/gad.342205 ↗
38. 10.1016/j.brainres.2015.05.01510.1016/j.brainres.2015.05.015 ↗
39. 10.1523/JNEUROSCI.1496-08.200810.1523/JNEUROSCI.1496-08.2008 ↗
40. 10.1101/gad.232470.11310.1101/gad.232470.113 ↗
41. 10.1113/jphysiol.2008.16092910.1113/jphysiol.2008.160929 ↗
42. 10.1016/j.neuron.2009.03.00110.1016/j.neuron.2009.03.001 ↗
43. 10.1016/j.neuron.2012.02.01310.1016/j.neuron.2012.02.013 ↗
44. 10.1523/JNEUROSCI.3737-05d.200610.1523/JNEUROSCI.3737-05d.2006 ↗
45. 10.1111/ejn.1260610.1111/ejn.12606 ↗
46. 10.1016/j.neuron.2015.09.03410.1016/j.neuron.2015.09.034 ↗
47. 10.1016/j.nbd.2016.01.00310.1016/j.nbd.2016.01.003 ↗
48. 10.1016/j.biopsych.2015.03.01310.1016/j.biopsych.2015.03.013 ↗
49. 10.1016/S0306-4522(02)00669-310.1016/S0306-4522(02)00669-3 ↗
50. 10.1038/nn.284210.1038/nn.2842 ↗
51. 10.1038/nn163410.1038/nn1634 ↗
52. 10.1152/jn.00645.200410.1152/jn.00645.2004 ↗
53. 10.1162/neco.2006.18.11.258310.1162/neco.2006.18.11.2583 ↗
54. 10.1523/JNEUROSCI.15-01-00030.199510.1523/JNEUROSCI.15-01-00030.1995 ↗
55. 10.1038/nature0183410.1038/nature01834 ↗
56. 10.1038/nn1209-148310.1038/nn1209-1483 ↗
57. 10.1016/j.neuron.2009.08.03710.1016/j.neuron.2009.08.037 ↗
58. 10.1016/j.neuron.2018.04.02510.1016/j.neuron.2018.04.025 ↗
59. 10.1016/j.neuron.2021.01.01410.1016/j.neuron.2021.01.014 ↗
60. 10.1016/j.tics.2010.09.00110.1016/j.tics.2010.09.001 ↗
61. 10.1126/science.112811510.1126/science.1128115 ↗
62. 10.1016/j.neuron.2023.06.01610.1016/j.neuron.2023.06.016 ↗
63. 10.3389/fnana.2014.0005210.3389/fnana.2014.00052 ↗
64. 10.1016/j.neures.2006.07.00710.1016/j.neures.2006.07.007 ↗
65. 10.1007/s00441-018-2882-210.1007/s00441-018-2882-2 ↗
66. 10.1038/nature0857310.1038/nature08573 ↗
67. 10.1038/nn.337910.1038/nn.3379 ↗
68. 10.1073/pnas.94.10.540110.1073/pnas.94.10.5401 ↗
69. 10.1016/j.gde.2006.12.00410.1016/j.gde.2006.12.004 ↗
70. 10.1002/ajmg.153310.1002/ajmg.1533 ↗
71. 10.1016/S0092-8674(02)00897-810.1016/S0092-8674(02)00897-8 ↗
72. 10.1038/nn.380310.1038/nn.3803 ↗
73. 10.1038/s41583-022-00599-010.1038/s41583-022-00599-0 ↗
74. 10.1016/j.neuron.2010.09.01710.1016/j.neuron.2010.09.017 ↗
75. 10.1016/j.neuron.2007.01.03110.1016/j.neuron.2007.01.031 ↗
76. 10.1016/j.neuron.2014.01.02110.1016/j.neuron.2014.01.021 ↗
77. 10.1016/j.neuron.2021.09.03310.1016/j.neuron.2021.09.033 ↗
78. 10.1038/nature0137410.1038/nature01374 ↗
79. 10.1016/j.neuron.2008.01.03410.1016/j.neuron.2008.01.034 ↗
80. 10.1152/jn.00524.200610.1152/jn.00524.2006 ↗
81. 10.1016/j.neuron.2016.11.01810.1016/j.neuron.2016.11.018 ↗
82. 10.1016/j.celrep.2023.11355910.1016/j.celrep.2023.113559 ↗