ArticleNeuroscience2011
Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: a potential model of geriatric depression.
Article in Neuroscience, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers, 2 of them syntheses that pooled it.
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Who cites it
49 citing papers in PubMed, 2 syntheses or guidelines pooled it, 100 citations in OpenAlex.
- The Effect of Tai Chi Chuan on Negative Emotions in Non-Clinical Populations: A Meta-Analysis and Systematic Review.International journal of environmental research and public health · 2019Pooled it
- The genetic overlap between mood disorders and cardiometabolic diseases: a systematic review of genome wide and candidate gene studies.Translational psychiatry · 2017Pooled it
- Influence of Lifestyle on Brain Sensitivity to Circulating Insulin-like Growth Factor 1.International journal of molecular sciences · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- Article
- Acute neuroendocrine changes after traumatic brain injury.Brain & spine · 2024Review
- Local autocrine plasticity signaling in single dendritic spines by insulin-like growth factors.Science advances · 2023Article
- Ketamine and the Disinhibition Hypothesis: Neurotrophic Factor-Mediated Treatment of Depression.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Identification of the molecular mechanism of insulin-like growth factor-1 (IGF-1): a promising therapeutic target for neurodegenerative diseases associated with metabolic syndrome.Cell & bioscience · 2023Review
- Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis.Frontiers in endocrinology · 2023Review
- Lower serum insulin-like growth factor 1 concentrations in patients with chronic insomnia disorder.Frontiers in psychiatry · 2023Article
- Article
- DNA Methylation Markers and Prediction Model for Depression and Their Contribution for Breast Cancer Risk.Frontiers in molecular neuroscience · 2022Article
- Preclinical and clinical evidence of IGF-1 as a prognostic marker and acute intervention with ischemic stroke.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Co-treatment of vitamin D supplementation with enriched environment improves synaptic plasticity and spatial learning and memory in aged rats.Psychopharmacology · 2021Article
- Hippocampal Neural Stem Cell Grafting after Status Epilepticus Alleviates Chronic Epilepsy and Abnormal Plasticity, and Maintains Better Memory and Mood Function.Aging and disease · 2020Article
- Article
- Disparate Central and Peripheral Effects of Circulating IGF-1 Deficiency on Tissue Mitochondrial Function.Molecular neurobiology · 2020Article
- Lifelong consequences of brain injuries during development: From risk to resilience.Frontiers in neuroendocrinology · 2019Review
- Neuroendocrine drivers of risk and resilience: The influence of metabolism & mitochondria.Frontiers in neuroendocrinology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Numerous studies support the hypothesis that deficiency of insulin-like growth factor I (IGF-1) in adults contributes to depression, but direct evidence is limited. Many psychological and pro-cognitive effects have been attributed to IGF-1, but appropriate animal models of adult-onset IGF-1 deficiency are lacking. In this study, we use a viral-mediated Cre-loxP system to knockout the Igf1 gene in either the liver, neurons of the CA1 region of the hippocampus, or both. Knockout of liver Igf1 reduced serum IGF-1 levels by 40% and hippocampal IGF-1 levels by 26%. Knockout of Igf1 in CA1 reduced hippocampal IGF-1 levels by 13%. The most severe reduction in hippocampal IGF-1 occurred in the group with knockouts in both liver and CA1 (36% reduction), and was associated with a 3.5-fold increase in immobility in the forced swim test. Reduction of either circulating or hippocampal IGF-1 levels did not alter anxiety measured in an open field and elevated plus maze, nor locomotion in the open field. Furthermore, local compensation for deficiencies in circulating IGF-1 did not occur in the hippocampus, nor were serum levels of IGF-1 upregulated in response to the moderate decline of hippocampal IGF-1 caused by the knockouts in CA1. We conclude that adult-onset IGF-1 deficiency alone is sufficient to induce a depressive phenotype in mice. Furthermore, our results suggest that individuals with low brain levels of IGF-1 are at increased risk for depression and these behavioral effects are not ameliorated by increased local IGF-1 production or transport. Our study supports the hypothesis that the natural IGF-1 decline in aging humans may contribute to geriatric depression.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.