Insulin-Like Growth Factors' Impact on Brain Development

Insulin-Like Growth Factors (IGFs) and Their Impact on Brain Development and Cognitive Function

Insulin-Like Growth Factors (IGFs), particularly IGF1 and IGF2, play crucial roles in brain development at different stages of life. These growth factors contribute to brain cell proliferation and differentiation in the fetus and early life, vascular support during fetal growth, and synaptic plasticity and memory in adulthood.

During the fetal stage, IGF1 produced by microglia in the developing human brain drives a rapid increase in interneurons, essential for building complex neural circuits and cognitive function. This microglia-produced IGF1 appears to be a unique evolutionary adaptation in humans supporting cortical development in early fetal stages [1][3]. IGF2, abundantly expressed in fetal tissue and the placenta, promotes angiogenesis and vascular development crucial for supporting brain growth and overall fetal development [2].

In early childhood, IGF1 signaling continues to support early-stage brain cells by promoting neuron proliferation, contributing to brain growth and plasticity during critical periods of childhood development [3]. Growth hormone pathways linked to IGFs are vital for overall physiological and brain development in this phase [4].

In adulthood, IGF2 remains important, particularly in the hippocampus, where it supports synaptic plasticity and memory formation. Reduced expression of IGF2 due to age-related epigenetic changes correlates with memory decline and impaired cognitive function. Experimental enhancement of IGF2 expression in adult hippocampus improves memory and synaptic function, highlighting IGF2’s role in maintaining cognitive health [5].

IGFs are vital in synaptic formation and maintenance, crucial for efficient neural communication. They help in the modulation of neurotransmitter systems, affecting neural communication and brain function. However, overactivation of IGF pathways could lead to unwanted side effects, including an increased risk of certain cancers [6].

Conditions such as Alzheimer's disease, Parkinson's disease, and other neurodegenerative disorders have been linked to dysregulated IGF signaling [7]. Higher levels of IGF-1 are associated with improved cognitive performance in both animal models and human studies [8]. IGF-1 has been studied for its neuroprotective properties, offering potential in slowing the progression of neurodegenerative diseases [9].

IGF-1 binds to its receptor on the surface of neurons, initiating a cascade of intracellular signaling pathways that can lead to promoting cell survival, stimulating cell growth, and influencing cell migration [10]. IGF-1 has been shown to affect the dopaminergic system, which is involved in reward, motivation, and motor control [11].

In summary, IGFs play a significant role in cognitive processes such as learning, memory, and decision-making, making them promising targets for further research in the field of neuroscience and cognitive health.

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