IGF-1neurotrophic factorneurogenesisBDNFsynaptic plasticityIGF-1Rsomatotropic axiscognition

IGF-1 and the Brain: Neurotrophic Research

A research overview of insulin-like growth factor 1 in the brain: how it reaches and is made in the CNS, its receptor signalling, its neurotrophic roles in neurogenesis and plasticity, and the mixed evidence on IGF-1 and cognition.

18 June 20265 min read

This article is for research and educational purposes only and is not medical advice. It describes endogenous physiology and what research has examined, not benefits, dosing, or outcomes.

Introduction

Insulin-like growth factor 1 (IGF-1) is best known as the downstream mediator of growth hormone in the body, but it is also one of the most studied growth factors inside the brain. Research characterises it as a neurotrophic factor involved in how neurons survive, how new neurons are generated, and how synapses adapt. This article summarises that literature, and, importantly, where the evidence is mixed.

Quick answer: IGF-1 reaches the brain from the circulation (it is actively transported across the blood-brain barrier) and is also produced locally by brain cells. Acting through the IGF-1 receptor, a receptor tyrosine kinase, it is described in research as a neurotrophic factor that modulates neuronal survival, adult neurogenesis, and synaptic plasticity. Its relationship to cognition across the lifespan is an active and conflicting area of research, not a settled "more is better" story.

IGF-1 in the Brain

There are two sources of brain IGF-1. First, circulating (largely liver-derived) IGF-1 is actively transported across the blood-brain barrier throughout life. Second, IGF-1 is produced locally within the CNS by all major cell types, neurons and glia, with local expression peaking around birth, then declining but persisting in neurogenic regions such as the dentate gyrus, olfactory bulb, and cerebellum. IGF-1 is structurally similar to insulin and is one of the "insulin-like peptides" (with insulin and IGF-2) that act in the brain.

The IGF-1 Receptor and Signalling

IGF-1 acts through the IGF-1 receptor (IGF-1R), a receptor tyrosine kinase that is widely expressed across the brain and concentrated in neuron-rich areas (the granule cell layers of the olfactory bulb, the dentate gyrus, the cerebellar cortex), with little in white matter. Downstream, IGF-1R signals through the canonical PI3K-Akt and Ras-Raf-MAPK (ERK) pathways, the same intracellular machinery that underlies many of its trophic effects.

A Neurotrophic Factor

The research literature characterises IGF-1 as a bona fide neurotrophic factor that modulates the generation and function of major brain cell types. Roles that have been studied include neuronal survival, adult neurogenesis (especially in the hippocampus), synaptic plasticity, and brain development and maturation. These are mechanistic and largely preclinical findings about endogenous IGF-1, descriptions of biology, not claims about an intervention.

Exercise, Neurogenesis, and BDNF

Two influential rodent studies tie IGF-1 to the brain effects of exercise. In one, circulating IGF-1 was shown to mediate exercise-induced increases in the number of new neurons in the adult hippocampus, blocking blood-borne IGF-1 from entering the brain inhibited that exercise effect (Trejo, Carro & Torres-Alemán, 2001). In another, blocking the hippocampal IGF-1 receptor during voluntary exercise reversed exercise-induced increases in BDNF and its downstream signalling, implicating IGF-1 in some of the synaptic-plasticity effects of exercise (Ding et al., 2006). Both are animal studies of endogenous IGF-1; they describe mechanism, not a human outcome a reader could expect.

IGF-1 and Cognition Across the Lifespan

The GH/IGF-1 (somatotropic) axis has been associated with cognitive function across life, and declining serum IGF-1 has been correlated with age-related cognitive decline in some research. But this is where caution matters: the broader literature is explicitly conflicting. Reduced IGF-1 signalling has, paradoxically, been linked to extended lifespan in model organisms, and reviews note the evidence does not support a clean "more IGF-1 equals a better brain" narrative. The honest summary is an association under active debate, not a directional health claim.

The GH to IGF-1 Axis

Upstream of all of this sits the somatotropic axis: pituitary growth hormone drives IGF-1 production, the relationship framed historically by the somatomedin hypothesis (later refined to recognise locally produced, autocrine/paracrine IGF-1 alongside circulating liver-derived IGF-1). For a research-focused overview of growth hormone and the IGF-1 axis, see the growth hormone and the IGF-1 axis research guide.

Frequently Asked Questions

Where does the brain's IGF-1 come from? Two places: circulating IGF-1 (largely liver-derived) is actively transported across the blood-brain barrier throughout life, and IGF-1 is also produced locally by neurons and glia, especially during development and in neurogenic regions thereafter.

What does IGF-1 do in the brain, according to research? It is characterised as a neurotrophic factor involved in neuronal survival, adult neurogenesis (notably hippocampal), and synaptic plasticity, signalling through the IGF-1 receptor via PI3K-Akt and MAPK pathways. These are mechanistic research findings, not outcomes.

Is IGF-1 linked to exercise and BDNF? In rodent studies, circulating IGF-1 mediated exercise-induced hippocampal neurogenesis, and blocking the hippocampal IGF-1 receptor reversed exercise-induced BDNF increases, implicating IGF-1 in some exercise-related plasticity effects in animals.

Does more IGF-1 mean better cognition? No, the evidence is mixed. Lower IGF-1 is associated with age-related cognitive decline in some studies, yet reduced IGF-1 signalling is linked to longer lifespan in models. It is an unresolved research association, not a basis for any intervention.

References

  • Fernandez AM, Torres-Alemán I. The many faces of insulin-like peptide signalling in the brain. Nat Rev Neurosci. 2012;13(4):225-239. PMID 22430016
  • Wrigley S, Arafa D, Tropea D. Insulin-Like Growth Factor 1: At the Crossroads of Brain Development and Aging. Front Cell Neurosci. 2017;11:14. PMID 28203146
  • Nuñez A, Zegarra-Valdivia J, Fernandez de Sevilla D, Pignatelli J, Torres-Aleman I. The neurobiology of insulin-like growth factor I. Mol Psychiatry. 2023;28(8):3220-3230. PMID 37353586
  • Dyer AH, Vahdatpour C, Sanfeliu A, Tropea D. The role of IGF-1 in brain development, maturation and neuroplasticity. Neuroscience. 2016;325:89-99. PMID 27038749
  • Trejo JL, Carro E, Torres-Aleman I. Circulating IGF-I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci. 2001;21(5):1628-1634. PMID 11222653
  • Ding Q, Vaynman S, Akhavan M, Ying Z, Gomez-Pinilla F. IGF-1 interfaces with BDNF-mediated synaptic plasticity... Neuroscience. 2006;140(3):823-833. PMID 16650607
  • Aleman A, Torres-Alemán I. Circulating IGF-I and cognitive function: neuromodulation throughout the lifespan. Prog Neurobiol. 2009;89(3):256-265. PMID 19665513

Further Reading