Table 1 IGF-1-deficient-induced neurological disease

1

LID Mice

IGF-1 deficient cause neuro-glio-vascular unit damage

[188]

2

IGF1R (VE-Cadherin-Cre^ERT2/Igf1r^f/f)

IGF-1 is critical for cerebromicrovascular endothelial health and maintenance of normal neurovascular coupling (NVC) responses

[189]

3

IGF1R (GFAP-Cre^ERT2/Igf1r^f/f)

IGF-1 promotes astrocyte health and maintains normal NVC, protecting cognitive health

[45]

4

AD clinical study

The IGF-1 level was increased in AD subjects’ serum but not in CSF

[190]

5

Aged LID mice

IGF-1 is essential for the regulation of mitochondrial function, redox status, and cognition, and IGF-1 deficiency with age may increase brain damage and cognitive deficits

[191]

6

igfr^f/f mice

Reduced IGF-1 increases the accumulation of extrasynaptic glutamate, which may contribute to neurodegeneration in disease states

[192]

7

IGFR (GFAP-Cre^TAM/igfr^f/f)

Reduction in IGFR expression with age is associated with a decrease in hippocampal-dependent learning and increased gliosis

[193]

8

MS clinical study

Low serum IGF-1 was associated with cognitive impairment and fatigue in MS

[194]

9

AD and vascular dementia (VaD) clinical study

Low serum IGF-1 was a risk marker for VaD

[195]

10

AD clinical study

Lower baseline serum IGF-1 was associated with a faster cognitive decline in AD over a 2-year period

[196]

11

IGF-1 deficient mice (Igf1^f/f + TBG-Cre-AAV8)

IGF-1 deficiency exerts deleterious effects on cerebral microcirculation, causes a decline in cortical and hippocampal capillarity, and exacerbates hypertension-induced cerebromicrovascular rarefaction

[42]

12

AD clinical study

Increased levels of circulating IGF-1 and IGFBP-3 cause differences in mean age and MMSE scores, and circulating levels of IGFBP-3 decrease the level of IGF-1

[197]

13

AD clinical study

Lower serum IGF-1 was associated with cognitive impairment and was involved in the pathogenesis of cognitive deficits in AD

[84]

14

Postnatal/adult global IGF-I knockout (KO) mice (Igf-I2/2)

IGF-1 regulates postnatal/adult hippocampal neurogenesis in a stage-dependent manner

[198]

15

IGF-1 deficiency (Igf1(f/f)-TBG-Cre-AAV8)

IGF-1 deficiency also impaired glutamate-mediated CBF responses, likely due to dysregulation of astrocytic expression of metabotropic glutamate receptors and impaired mediation of CBF responses by eicosanoid gliotransmitters

[169]

16

IGF-1 deficiency (Igf1(f/f) -TBG-Cre-AAV8)

IGF-1-deficient mice included exacerbated disruption of the BBB and neuroinflammation that were associated with impaired hippocampal cognitive function

[164]

17

Prenatal stress/Dawley/Adult male offspring IGF-1, 10–20 µg/h/i.c.v

IGF-1 administration decreased IGF-1 levels and IGF-1 phosphorylation with altered IRS-1 phosphorylation in the hippocampus and frontal cortex of prenatal stress-induced rats

[199]

18

AD clinical study

Reduced serum IGF-1 is associated with the development of AD dementia in patients with AD

[82]

19

Clinical study IGF-1R mutation

IGF-1R mutations lead to prenatal and postnatal growth retardation and microcephaly

[27]

20

AD clinical study

Patients with AD as well as other dementias had high levels of IGF-1 in serum but not in CSF

[200]

21

AD clinical study

Low serum levels of IGF-1 and IGFBP-3 in males with AD but not in females with AD

[201]

22

Viral-mediated Cre-lox P system to knockout the Igf1 gene animal model

Adult-onset IGF-1 deficiency alone is sufficient to induce a depressive phenotype in mice

Individuals with low brain IGF-1 levels are at increased risk for depression, and these behavioral effects are not ameliorated by increased local IGF-1 production or transport

[202]

23

AD clinical study

Significant decreases in IRS-1 and IRS-2 levels were identified in AD neurons in association with increased levels of inactivated phosphor (Ser312) IRS-1 and phosphor(Ser616)IRS-1, where increased levels of these phosphoserine epitopes colocalized strongly with NFTs

[203]

24

APP (SW), Tg2576 mice

Impaired IGF-1/IRS-2 signaling prevents premature death and delays amyloid accumulation in a model of AD

[204]

25

IGF-1R^± mice/MPTP induction

IGF-1R^± mice have shown increased dopamine neuronal loss in MPTP-induced mice

[96]

26

AD clinical study

Patients with vascular dementia and AD had low IGF-1 that may cause carotid atherosclerosis

[205]

27

Clinical cohort study IGF-1 and IGF-1R mutation

IGF-1 and IGF-1R mutant children had intrauterine growth retardation and poor postnatal growth

[26]

28

Brain injury-induced Romney-Suffolk fetal sheep/IGF-1 (3 or 30 μg/i.c.v)

IGF-1 treatment reduced caspase-3 activation and increased glial proliferation in a dose-dependent manner

[31]