Protective effects of vitamin D on learning and memory deficit induced by scopolamine in male rats: the roles of brain-derived neurotrophic factor and oxidative stress

Naunyn Schmiedebergs Arch Pharmacol. 2021 Jul;394(7):1451-1466. doi: 10.1007/s00210-021-02062-w. Epub 2021 Mar 2.

Abstract

The beneficial effects of vitamin D (vit D) on central nervous system disorders have been suggested. In the current research, the protective effects of vit D on learning and memory deficit induced by scopolamine, oxidative stress criteria, brain-derived neurotrophic factor (BDNF), and nitric oxide (NO) in the brain were investigated. Rats were divided into five groups, including (1) Control, (2) Scopolamine (2 mg/kg), (3-5) Scopolamine + Vit D (100, 1000, and 10,000 IU/kg) groups. Vit D administrated for 2 weeks and in the third week scopolamine co-administrated with vit D and behavioral tests, including Morris water maze (MWM) and passive avoidance (PA) tests, were carried out. The cortical and hippocampal tissues were analyzed for BDNF, catalase (CAT), and superoxide dismutase (SOD) activities, thiol content, NO metabolites, and malondialdehyde (MDA) concentration. Scopolamine injection significantly impaired rats' performance on the MWM and PA test. It further enhanced the MDA and nitrite level while decreased thiol content and BDNF levels and SOD and CAT activities in the brain. Administration of both 1000 and 10,000 IU/kg vit D improved cognitive outcome in MWM and PA tests. In addition, vit D elevated thiol content, SOD and CAT activities, and BDNF levels, while reduced nitrite and MDA concentration. Vit D also increased the levels of vit D and calcium in the serum. The results demonstrated that vit D has protective effects on scopolamine-associated learning and memory impairment by improving BDNF levels and attenuating NO and brain tissue oxidative damage.

Keywords: Brain-derived neurotrophic factor; Learning; Memory; Nitric oxide; Oxidative stress; Scopolamine; Vitamin D.

MeSH terms

  • Adjuvants, Anesthesia / toxicity
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Dose-Response Relationship, Drug
  • Learning / drug effects
  • Learning / physiology
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / metabolism*
  • Memory Disorders / prevention & control*
  • Nitric Oxide / antagonists & inhibitors
  • Nitric Oxide / metabolism
  • Oxidative Stress / drug effects*
  • Oxidative Stress / physiology
  • Rats
  • Rats, Wistar
  • Scopolamine / toxicity*
  • Vitamin D / pharmacology
  • Vitamin D / therapeutic use*

Substances

  • Adjuvants, Anesthesia
  • Antioxidants
  • Bdnf protein, rat
  • Brain-Derived Neurotrophic Factor
  • Vitamin D
  • Nitric Oxide
  • Scopolamine