Predisposition to cortical neurodegenerative changes in brains of hypertension prone rats

Moti Ben-Shabat, Yaseen Awad-Igbaria, Shifra Sela, Bella Gross, Yoram Yagil, Chana Yagil, Eilam Palzur

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: Substantial evidence suggests that hypertension is a significant risk factor for cognitive decline. However, it is unclear whether the genetic predisposition to hypertension is also associated with cellular dysfunction that promotes neurodegeneration. Methods: Changes in blood pressure were evaluated following dietary salt-loading or administration of a regular diet in Sabra Normotensive (SBN/y) and Sabra Hypertension-prone rats (SBH/y). We performed quantitative RT-PCR and immunofluorescence staining in brain cortical tissues before salt loading and 6 and 9 months after salt loading. To examine the expression of brain cortical proteins involved in the gene regulation (Histone Deacetylase-HDAC2; Histone Acetyltransferase 1-HAT1), stress response (Activating Transcription Factor 4-ATF4; Eukaryotic Initiation Factor 2- eIF2α), autophagy (Autophagy related 4A cysteine peptidase- Atg4a; light-chain 3-LC3A/B; mammalian target of rapamycin complex 1- mTORC1) and apoptosis (caspase-3). Results: Prior to salt loading, SBH/y compared to SBN/y expressed a significantly higher level of cortical HAT1 (protein), Caspase-3 (mRNA/protein), LC3A, and ATF4 (mRNA), lower levels of ATG4A (mRNA/protein), LC3A/B, HDAC2 (protein), as well as a lower density of cortical neurons. Following dietary salt loading, SBH/y but not SBN/y developed high blood pressure. In hypertensive SBH/y, there was significant upregulation of cortical HAT1 (protein), Caspase-3 (protein), and eIF2α ~ P (protein) and downregulation of HDAC2 (protein) and mTORC1 (mRNA), and cortical neuronal loss. Conclusions: The present findings suggest that genetic predisposition to hypertension is associated in the brain cortex with disruption in autophagy, gene regulation, an abnormal response to cellular stress, and a high level of cortical apoptosis, and could therefore exacerbate cellular dysfunction and thereby promote neurodegeneration.

Original languageEnglish
Article number51
JournalJournal of Translational Medicine
Volume21
Issue number1
DOIs
StatePublished - 1 Dec 2023

Keywords

  • Dietary Salt Loading
  • Genetic predisposition
  • Hypertension
  • Neurodegeneration
  • SBH/y
  • SBN/y

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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