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

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:

• Iron deficiency
• Growth factors
• Central nervous system

Acknowledgements

José A. Estrada and Irazú Contreras contributed equally to this work.