2. Academic Validation
  3. Nerol ameliorates cognitive dysfunction in vascular dementia rats by inhibiting mitochondrial oxidative stress and reducing hippocampal senescence

Nerol ameliorates cognitive dysfunction in vascular dementia rats by inhibiting mitochondrial oxidative stress and reducing hippocampal senescence

  • Brain Res Bull. 2026 Feb:235:111753. doi: 10.1016/j.brainresbull.2026.111753.
Jing Yang 1,  Qian-Qian Niu 2,  Na Liu 3,  Bo Wang 4,  Ya-Jun Shen 5,  De-Sheng Liu 6,  Xiao-Wen Li 7,  Mo-Li Zhu 8,  Qian-Qian Wang 9,  Ya-Qi Guo 10
Affiliations

Affiliations

  • 1 Puyang Medical College, Puyang 457000, China. Electronic address: [email protected].
  • 2 Henan Medical University, Xinxiang 453003, China. Electronic address: [email protected].
  • 3 Puyang Medical College, Puyang 457000, China. Electronic address: [email protected].
  • 4 Puyang Medical College, Puyang 457000, China. Electronic address: [email protected].
  • 5 Puyang Medical College, Puyang 457000, China. Electronic address: [email protected].
  • 6 Puyang Medical College, Puyang 457000, China. Electronic address: [email protected].
  • 7 Puyang Medical College, Puyang 457000, China. Electronic address: [email protected].
  • 8 Henan Medical University, Xinxiang 453003, China. Electronic address: [email protected].
  • 9 Henan Medical University, Xinxiang 453003, China. Electronic address: [email protected].
  • 10 College of Pharmacy, North Henan Medical University, Xinxiang 453003, China. Electronic address: [email protected].
PMID: 41619816 DOI: 10.1016/j.brainresbull.2026.111753
Abstract

Vascular dementia (VaD) is a neurodegenerative disease caused by chronic cerebral hypoperfusion and is mainly characterized by cognitive dysfunction. This study established a VaD rat model using permanent bilateral common carotid artery occlusion (2-VO), administered different doses of nerol for 8 weeks, and evaluated cognitive function using the Morris water maze and Y-maze tests, while systematically analyzing hippocampal neuronal structure, senescence, mitochondrial function, oxidative stress, and apoptosis-related changes. The results showed that nerol improved spatial learning, memory ability, and exploratory behavior in VaD rats, and alleviated hippocampal neuronal structural damage and dendritic degeneration. At the same time, nerol reduced the number of senescence-associated β-galactosidase-positive and TUNEL-positive cells and downregulated the expression of p53 and p21. Mechanistically, nerol inhibited NOX2/NOX4-mediated Reactive Oxygen Species production, enhanced antioxidant capacity, stabilized mitochondrial membrane potential, and suppressed DRP1/FIS1-mediated abnormal mitochondrial fission, thereby potentially attenuating oxidative stress-related neuronal senescence and Apoptosis and improving cognitive function. These findings provide experimental evidence supporting the potential therapeutic value of nerol in vascular dementia.

Keywords

Mitochondrial oxidative stress; Nerol; Senescence; VaD.

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