Activation of the RARα Attenuated CSF Hypersecretion to Inhibit Hydrocephalus Development via Regulating the MAFB/MSR1 Pathway

Hanhai Zeng; Kaibo Yu; Junyou Wang; Jingya Ye; Huaijun Chen; Chaoran Xu; Ting Chen; Feng Yan; Gao Chen; Chi Gu

doi:10.3390/ijms24032586

Activation of the RARα Attenuated CSF Hypersecretion to Inhibit Hydrocephalus Development via Regulating the MAFB/MSR1 Pathway

Int J Mol Sci. 2023 Jan 30;24(3):2586. doi: 10.3390/ijms24032586.

Authors

Hanhai Zeng^{1

2}, Kaibo Yu^{1

2}, Junyou Wang³, Jingya Ye³, Huaijun Chen^{1

2}, Chaoran Xu^{1

2}, Ting Chen^{1

2}, Feng Yan^{1

2}, Gao Chen^{1

2}, Chi Gu^{1

2}

Affiliations

¹ Department of Neurological Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
² Key Laboratory of Precise Treatment and Clinical Translational Research of Neurological Diseases, Zhejiang University, Hangzhou 310003, China.
³ School of Medicine, Zhejiang University, Hangzhou 310030, China.

Abstract

Hydrocephalus has been observed in rats with spontaneous hypertension (SHRs). It has been demonstrated that activation of the oxidative stress related protein retinoic acid receptor alpha (RARα) has neuroprotective impacts. Our investigation aims to determine the potential role and mechanism of RARα in hydrocephalus. The RARα-specific agonist (Am80) and RARα inhibitor (AGN196996) were used to investigate the role of RARα in cerebrospinal fluid (CSF) secretion in the choroid plexus of SHRs. Evaluations of CSF secretion, ventricular volume, Western blotting, and immunofluorescent staining were performed. Hydrocephalus and CSF hypersecretion were identified in SHRs but not in Wistar-Kyoto rats, occurring at the age of 7 weeks. The RARα/MAFB/MSR1 pathway was also activated in SHRs. Therapy with Am80 beginning in week 5 decreased CSF hypersecretion, hydrocephalus development, and pathological changes in choroid plexus alterations by week 7. AGN196996 abolished the effect of Am80. In conclusion, activation of the RARα attenuated CSF hypersecretion to inhibit hydrocephalus development via regulating the MAFB/MSR1 pathway. RARα may act as a possible therapeutic target for hydrocephalus.

Keywords: CSF; MSR1; RARα; hydrocephalus; spontaneous hypertensive rat.

MeSH terms

Animals
Choroid Plexus / metabolism
Hydrocephalus* / metabolism
Hypertension* / metabolism
MafB Transcription Factor / metabolism
Oncogene Proteins / metabolism
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Scavenger Receptors, Class A / metabolism

Substances

Mafb protein, rat
MafB Transcription Factor
Oncogene Proteins
tamibarotene
Scavenger Receptors, Class A
Rara protein, rat

Grants and funding

This work was supported by the National Natural Science Foundation of China (81901234, 81971099, 82171273), the National Key R&D Program of China (2018YFC1312600, 2018YFC1312603), and the Key R&D Program of Zhejiang (2022C03133).