ITPR2 Mediated Calcium Homeostasis in Oligodendrocytes is Essential for Myelination and Involved in Depressive-Like Behavior in Adolescent Mice.

Publisher: WILEY-VCH Country of Publication: Germany NLM ID: 101664569 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2198-3844 (Electronic) Linking ISSN: 21983844 NLM ISO Abbreviation: Adv Sci (Weinh) Subsets: MEDLINE

Original Publication: Weinheim : WILEY-VCH, [2014]-

Calcium*/metabolism ; Depression*/metabolism ; Depression*/genetics ; Inositol 1,4,5-Trisphosphate Receptors*/metabolism ; Inositol 1,4,5-Trisphosphate Receptors*/genetics ; Myelin Sheath*/metabolism ; Oligodendroglia*/metabolism; Animals ; Mice ; Behavior, Animal ; Cell Differentiation/genetics ; Disease Models, Animal ; Homeostasis/genetics

Ca ²⁺ signaling is essential for oligodendrocyte (OL) development and myelin formation. Inositol 1,4,5-trisphosphate receptor type 2 (ITPR2) is an endoplasmic reticulum calcium channel and shows stage-dependent high levels in postmitotic oligodendrocyte precursor cells (OPCs). The role and potential mechanism of ITPR2 in OLs remain unclear. In this study, it is revealed that loss of Itpr2 in OLs disturbs Ca ²⁺ homeostasis and inhibits myelination in adolescent mice. Animals with OL-specific deletion of Itpr2 exhibit anxiety/depressive-like behaviors and manifest with interrupted OPC proliferation, leading to fewer mature OLs in the brain. Detailed transcriptome profiling and signal pathway analysis suggest that MAPK/ERK-CDK6/cyclin D1 axis underlies the interfered cell cycle progression in Itpr2 ablated OPCs. Besides, blocking MAPK/ERK pathway significantly improves the delayed OPC differentiation and myelination in Itpr2 mutant. Notably, the resting [Ca ²⁺ ] i is increased in Itpr2 ablated OPCs, with the elevation of several plasma calcium channels. Antagonists against these plasma calcium channels can normalize the resting [Ca ²⁺ ] i level and enhance lineage progression in Itpr2-ablated OPCs. Together, the findings reveal novel insights for calcium homeostasis in manipulating developmental transition from OPCs to pre-OLs; additionally, the involvement of OLs-originated ITPR2 in depressive behaviors provides new therapeutic strategies to alleviate myelin-associated psychiatric disorders.
(© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Science. 2015 Mar 6;347(6226):1138-42. (PMID: 25700174)
Eur J Neurosci. 2021 Jan;53(1):281-297. (PMID: 31736197)
Eur Arch Psychiatry Clin Neurosci. 2022 Sep;272(6):947-955. (PMID: 34822006)
Neurosci Lett. 2019 Jan 18;690:202-209. (PMID: 30366011)
J Comp Neurol. 2017 Jun 1;525(8):1922-1933. (PMID: 28118485)
Neuropsychopharmacology. 2021 Dec;46(13):2295-2303. (PMID: 34215842)
Pflugers Arch. 2018 May;470(5):705-716. (PMID: 29569183)
Cardiovasc Res. 2011 Nov 1;92(2):307-16. (PMID: 21840882)
Science. 2005 Sep 30;309(5744):2232-4. (PMID: 16195467)
Brain Struct Funct. 2017 Sep;222(7):2993-3005. (PMID: 28247021)
J Neurosci. 2013 Jan 2;33(1):175-86. (PMID: 23283332)
Development. 2011 Feb;138(4):745-53. (PMID: 21266410)
Front Nutr. 2023 Feb 09;10:1042522. (PMID: 36845060)
Front Mol Neurosci. 2018 May 18;11:162. (PMID: 29867353)
Proc Natl Acad Sci U S A. 2018 Aug 28;115(35):E8246-E8255. (PMID: 30108144)
Nat Rev Neurosci. 2018 Jan;19(1):49-58. (PMID: 29118449)
Sci Rep. 2016 Aug 24;6:31599. (PMID: 27554391)
Eur Arch Psychiatry Clin Neurosci. 2019 Jun;269(4):387-395. (PMID: 29980921)
Am J Hum Genet. 2017 Jun 1;100(6):969-977. (PMID: 28575651)
J Affect Disord. 2011 Jul;132(1-2):26-36. (PMID: 20889213)
J Biol Chem. 1996 Aug 23;271(34):20608-16. (PMID: 8702807)
Cell Rep. 2021 May 18;35(7):109147. (PMID: 34010640)
Environ Sci Technol. 2022 Aug 16;56(16):11536-11546. (PMID: 35895862)
Cell Mol Life Sci. 2001 Jan;58(1):80-93. (PMID: 11229819)
Cell Rep. 2020 Mar 10;30(10):3466-3477.e4. (PMID: 32160550)
Nat Med. 2013 Jun;19(6):773-7. (PMID: 23644515)
Mol Psychiatry. 2021 Jan;26(1):103-117. (PMID: 33144710)
Psychoneuroendocrinology. 2018 May;91:198-205. (PMID: 29587243)
Cell Res. 2000 Mar;10(1):1-16. (PMID: 10765979)
Adv Sci (Weinh). 2024 May;11(20):e2306498. (PMID: 38476116)
Front Behav Neurosci. 2014 Nov 12;8:384. (PMID: 25429263)
Med J Aust. 2013 Sep 16;199(S6):S28-31. (PMID: 25370281)
Science. 2021 Nov 12;374(6569):eaba6905. (PMID: 34618550)
Glia. 2019 Jul;67(7):1320-1332. (PMID: 30815939)
Nat Commun. 2021 Aug 24;12(1):5091. (PMID: 34429415)
Br J Psychiatry. 2012 Jul;201(1):33-9. (PMID: 22576724)
J Neurosci. 2011 Mar 9;31(10):3625-37. (PMID: 21389218)
Nat Neurosci. 2020 Mar;23(3):363-374. (PMID: 32066987)
Br J Pharmacol. 2005 Jun;145(4):527-34. (PMID: 15821750)
Cell Mol Life Sci. 2022 Aug 24;79(9):495. (PMID: 36001172)
Front Pharmacol. 2019 Apr 05;10:332. (PMID: 31024304)
J Neurosci. 2016 Jan 20;36(3):957-62. (PMID: 26791223)
Nat Neurosci. 2020 Mar;23(3):375-385. (PMID: 32015540)
Int J Environ Res Public Health. 2023 Mar 01;20(5):. (PMID: 36901441)
Nat Neurosci. 2020 Jun;23(6):771-781. (PMID: 32341540)
J Neurosci. 2005 Feb 9;25(6):1354-65. (PMID: 15703389)
Annu Rev Neurosci. 2020 Jul 8;43:163-186. (PMID: 32075518)
Neuron. 1994 Jun;12(6):1207-21. (PMID: 8011335)
Proc Natl Acad Sci U S A. 2019 May 14;116(20):10156-10161. (PMID: 31028142)
Mol Cell Biol. 1994 Mar;14(3):2077-86. (PMID: 8114739)
Cell Mol Neurobiol. 2019 Nov;39(8):1071-1080. (PMID: 31222426)
Front Cell Neurosci. 2021 Sep 22;15:751439. (PMID: 34630045)
Neuroscience. 2016 Apr 5;319:146-54. (PMID: 26820594)
Nat Commun. 2021 May 31;12(1):3321. (PMID: 34059669)
J Neurochem. 2006 Oct;99(2):641-56. (PMID: 16836654)
Glia. 2020 Oct;68(10):2070-2085. (PMID: 32170885)
Nat Commun. 2022 Feb 7;13(1):728. (PMID: 35132099)

2021ZD0201704 STI 2030-Major Project; 82071271 National Natural Science Foundation of China; 82221001 National Natural Science Foundation of China

Keywords: ITPR2; calcium homeostasis; depressive‐like behaviors; oligodendrocytes

SY7Q814VUP (Calcium)
0 (Inositol 1,4,5-Trisphosphate Receptors)
0 (Ip3r2 protein, mouse)

Date Created: 20240313 Date Completed: 20240528 Latest Revision: 20240705

20240705

PMC11132048

10.1002/advs.202306498

38476116