Molecular mechanisms of cognitive impairment in iron deficiency: alterations in brain-derived neurotrophic factor and insulin-like growth factor expression and function in the central nervous system

Nutr Neurosci. 2014 Sep;17(5):193-206. doi: 10.1179/1476830513Y.0000000084. Epub 2013 Nov 26.

Abstract

Objective: The present review examines the relationship between iron deficiency and central nervous system (CNS) development and cognitive impairment, focusing on the cellular and molecular mechanisms related to the expression and function of growth factors, particularly the insulin-like growth factors I and II (IGF-I/II) and brain-derived neurotrophic factor (BDNF), in the CNS.

Methods: Nutritional deficiencies are important determinants in human cognitive impairment. Among these, iron deficiency has the highest prevalence worldwide. Although this ailment is known to induce psychomotor deficits during development, the precise molecular and cellular mechanisms underlying these alterations have not been properly elucidated. This review summarizes the available information on the effect of iron deficiency on the expression and function of growth factors in the CNS, with an emphasis on IGF-I/II and BDNF.

Results and discussion: Recent studies have shown that specific growth factors, such as IGF-I/II and BDNF, have an essential role in cognition, particularly in processes involving learning and memory, by the activation of intracellular-signaling pathways involved in cell proliferation, differentiation, and survival. It is known that nutritional deficiencies promote reductions in systemic and CNS concentrations of growth factors, and that altered expression of these molecules and their receptors in the CNS leads to psychomotor and developmental deficits. Iron deficiency may induce these deficits by decreasing the expression and function of IGF-I/II and BDNF in specific areas of the brain.

Keywords: Central nervous system; Growth factors; Iron deficiency.

Publication types

  • Review

MeSH terms

  • Anemia, Iron-Deficiency / complications
  • Anemia, Iron-Deficiency / pathology*
  • Animals
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cell Differentiation
  • Cell Proliferation
  • Central Nervous System / metabolism
  • Central Nervous System / physiopathology
  • Cognition Disorders / complications
  • Cognition Disorders / pathology*
  • Cognition*
  • Disease Models, Animal
  • Humans
  • Learning
  • Memory
  • Signal Transduction
  • Somatomedins / genetics
  • Somatomedins / metabolism*

Substances

  • Brain-Derived Neurotrophic Factor
  • Somatomedins