A Neonatal Mild Defect in Brain Insulin Signaling Predisposes a Subclinical Model of Sporadic Alzheimer's to Develop the Disease

Abstract

Brain insulin system dysfunction has been proposed as a key player in the pathogenesis of sporadic Alzheimer’s disease (sAD). Given this fact, an adult rat model for sAD has been developed by intracerebroventricular injection of a subdiabetogenic streptozotocin dosage (icv-STZ). A low dose of icv-STZ in adult rats leads to a subclinical model of Alzheimer’s disease. According to the brain developmental origin for sAD occurrence, the present study evaluated the effect of neonatal injection of icv-STZ on the development and progression of Alzheimer’s disease later in the adult animals treated with a low dose of icv-STZ. Although no alteration was observed in the rats receiving an adult low dose of icv-STZ, these animals displayed cognitive deficits if they were also treated neonatally with icv-STZ. These impairments were associated with altered gene expression of insulin receptor, tau and choline acetyltransferase, along with increased astrocyte and dark neuron densities in the hippocampus. This study highlights neonatal brain insulin system dysfunction in the programming of brain insulin signaling sensitivity and provides more evidence for the developmental origin of sAD.

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Data Availability

All data are presented in this paper and further information and requests for resources and reagents should be directed to and will be fulfilled by the authors.

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Acknowledgements

This work was supported by Ferdowsi University of Mashhad, Mashhad, Iran. The authors acknowledge Ferdowsi University of Mashhad.

Funding

This work was supported by Ferdowsi University of Mashhad, Mashhad, Iran [grant number 3/37058 confirmed on 08.04.2015 equal to 19.01.1394].

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Zohreh Abbasi performed the experiments and wrote the manuscript. Mohammad Mahdi Ghahramani Seno assisted in new reagents and tools. Masoud Fereidoni conceived, designed and supervised the project, wrote the manuscript and provided financial support.

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Correspondence to Masoud Fereidoni.

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All experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health (NIH Publication No. 8023, revised 1978) and approved by the Ethical Committee of Ferdowsi University of Mashhad (FUM) on 19.01.1394.

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Abbasi, Z., Ghahramani Seno, M. & Fereidoni, M. A Neonatal Mild Defect in Brain Insulin Signaling Predisposes a Subclinical Model of Sporadic Alzheimer's to Develop the Disease. J Mol Neurosci (2021). https://doi.org/10.1007/s12031-021-01797-8

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Keywords

  • STZ
  • Insulin receptor signaling
  • Sporadic Alzheimer’s disease