Intravitreal Interleukin-2 modifies retinal excitatory circuits and retinocollicular innervation

Espírito-Santo, Sheila; Nunes-Tavares, Nilson; Mendonça, Henrique Rocha; Serfaty, Claudio Alberto; Sholl‐Franco, Alfred; Campello-Costa, Paula

doi:10.1016/j.exer.2021.108442

Cited by 5 publications

(2 citation statements)

References 72 publications

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“…A striking finding was the decrease in hippocampal levels of IL-2, a cytokine classically associated with an inflammatory profile. This finding may be related to the decrease in STAT-3 activation, since the phosphorylation of this target increases the levels of this interleukin and its subsequent signaling [ 37 , 38 ]. One of the mechanisms that may influence STAT-3 phosphorylation is Aβ itself, as it is a negative allosteric modulator of the leptin receptor [ 39 ], with consequent decreased activation of downstream targets.…”

Section: Discussionmentioning

confidence: 99%

Reduction in Hippocampal Amyloid-β Peptide (Aβ) Content during Glycine-Proline-Glutamate (Gly-Pro-Glu) Co-Administration Is Associated with Changes in Inflammation and Insulin-like Growth Factor (IGF)-I Signaling

Frago,

Burgos-Ramos,

Rodríguez-Pérez

et al. 2024

IJMS

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Alzheimer’s disease (AD) is characterized by the deposition in the brain of senile plaques composed of amyloid-β peptides (Aβs) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE), has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 for 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1, and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme, was also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

show abstract

Section: Discussionmentioning

confidence: 99%

Reduction in Hippocampal Amyloid-β Peptide (Aβ) Content during Glycine-Proline-Glutamate (Gly-Pro-Glu) Co-Administration Is Associated with Changes in Inflammation and Insulin-like Growth Factor (IGF)-I Signaling

Frago,

Burgos-Ramos,

Rodríguez-Pérez

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…A striking finding was the decrease in hippocampal levels of IL-2, a cytokine classically associated with an inflammatory profile. This finding may be related to the decrease in STAT-3 activation, since phosphorylation of this target increases the levels of this interleukin and its subsequent signaling [34,35]. One of the mechanisms that may influence STAT-3 phosphorylation is Aβ itself, as it is a negative allosteric modulator of the leptin receptor [36], with consequent decreased activation of downstream targets.…”

Section: Discussionmentioning

confidence: 99%

Reduction in Hippocampal Aβ Content During Gly-Pro-Glu Co-Administration Is Associated with Changes in Inflammation and IGF-I Signaling

Frago,

Burgos-Ramos,

Rodríguez-Pérez

et al. 2024

Preprint

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Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

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Determinants of approved acetylcholinesterase inhibitor response outcomes in Alzheimer’s disease: relevance for precision medicine in neurodegenerative diseases

Lista¹,

Vergallo²,

Teipel³

et al. 2023

Ageing Research Reviews

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Intravitreal Interleukin-2 modifies retinal excitatory circuits and retinocollicular innervation

Cited by 5 publications

References 72 publications

Reduction in Hippocampal Amyloid-β Peptide (Aβ) Content during Glycine-Proline-Glutamate (Gly-Pro-Glu) Co-Administration Is Associated with Changes in Inflammation and Insulin-like Growth Factor (IGF)-I Signaling

Reduction in Hippocampal Amyloid-β Peptide (Aβ) Content during Glycine-Proline-Glutamate (Gly-Pro-Glu) Co-Administration Is Associated with Changes in Inflammation and Insulin-like Growth Factor (IGF)-I Signaling

Reduction in Hippocampal Aβ Content During Gly-Pro-Glu Co-Administration Is Associated with Changes in Inflammation and IGF-I Signaling

Determinants of approved acetylcholinesterase inhibitor response outcomes in Alzheimer’s disease: relevance for precision medicine in neurodegenerative diseases

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