The neuroprotective effect of curcumin against Cd-induced neurotoxicity and hippocampal neurogenesis promotion through CREB-BDNF signaling pathway

Toxicology. 2020 Sep:442:152542. doi: 10.1016/j.tox.2020.152542. Epub 2020 Jul 28.

Abstract

Heavy metal neurotoxicity is one of the major challenges in today's era due to the large scale and widespread mechanisation of the production. However, the causative factors responsible for neurotoxicity are neither known nor do we have the availability of therapeutic approaches to deal with it. One of the major causative agents of neurotoxicity is a non-essential transition heavy metal, Cadmium (Cd), that reaches the central nervous system (CNS) through the nasal mucosa and olfactory pathway causing adverse structural and functional effects. In this study, we explored the neuroprotective efficacy of plant derived Curcumin which is reported to have pleiotropic biological activity including anti-oxidant, anti-inflammatory, anti-apoptotic, anti-carcinogenic and anti-angiogenic effects. Four different concentrations of curcumin (20, 40, 80 and 160 mg/kg of the body weight) were used to assess the behavioural, biochemical, hippocampal proteins (BDNF, CREB, DCX and Synapsin II) and histological changes in Swiss Albino mice that were pre-treated with Cd (2.5 mg/kg). The findings showed that Cd exposure led to the behavioural impairment through oxidative stress, reduction of hippocampal neurogenesis associated proteins, and degeneration of CA3 and cortical neurons. However, treatment of different curcumin concentrations had effectively restored the behavioural changes in Cd-exposed mice through regulation of oxidative stress and up-regulation of hippocampal proteins in a dose-dependent manner. Significantly, a dose of 160 mg/kg body weight was found to be glaringly effective. From this study, we infer that curcumin reverses the adverse effects of neurotoxicity induced by Cd and promotes neurogenesis.

Keywords: Curcumin; Neurodegeneration; Neurogenesis; Neuroprotection, neuroplasticity; Neurotoxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety / prevention & control
  • Anxiety / psychology
  • Behavior, Animal / drug effects
  • Brain-Derived Neurotrophic Factor / drug effects*
  • CA3 Region, Hippocampal / cytology
  • CA3 Region, Hippocampal / drug effects
  • Cadmium Poisoning / prevention & control*
  • Cadmium Poisoning / psychology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Curcumin / pharmacology*
  • Cyclic AMP Response Element-Binding Protein / drug effects*
  • Doublecortin Protein
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Maze Learning / drug effects
  • Mice
  • Neurogenesis / drug effects*
  • Neuroprotective Agents / pharmacology*
  • Neurotoxicity Syndromes / prevention & control*
  • Neurotoxicity Syndromes / psychology
  • Oxidative Stress / drug effects
  • Psychomotor Performance / drug effects
  • Signal Transduction / drug effects*

Substances

  • Bdnf protein, mouse
  • Brain-Derived Neurotrophic Factor
  • Creb1 protein, mouse
  • Cyclic AMP Response Element-Binding Protein
  • Dcx protein, mouse
  • Doublecortin Protein
  • Neuroprotective Agents
  • Curcumin