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

Abbasi, Zohreh; Seno, Mohammad Mahdi Ghahramani; Fereidoni, Masoud

doi:10.1007/s12031-021-01797-8

Cited by 3 publications

(4 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Injury to these cells is considered one of the mechanisms of brain insulin resistance in the intracerebroventricular (i.c.v) STZ model of Alzheimer’s disease [46]. Repeated i.c.v-STZ administrations in the neonatal and adult period leads to upregulation of insulin receptor mRNA expression in the adult hippocampus [47]. Conversely, systemic STZ administration does not alter brain insulin receptor expression in adult rats [19, 48].…”

Section: Discussionmentioning

confidence: 99%

Intranasal Insulin Attenuates the Long-Term Adverse Effects of Neonatal Hyperglycemia on the Hippocampus in Rats

et al. 2022

View full text Add to dashboard Cite

Hyperglycemia due to relative hypoinsulinism is common in extremely preterm infants and is associated with hippocampus-mediated long-term cognitive impairment. In neonatal rats, hypoinsulinemic hyperglycemia leads to oxidative stress, altered neurochemistry, microgliosis and abnormal synaptogenesis in the hippocampus. Intranasal insulin (INS) bypasses the blood-brain barrier, targets the brain and improves synaptogenesis in rodent models, and memory in adult humans with Alzheimer’s Disease or type 2 diabetes, without altering the blood levels of insulin or glucose. To test whether INS improves hippocampal development in neonatal hyperglycemia, rat pups were subjected to hypoinsulinemic hyperglycemia by injecting streptozotocin (STZ) at a dose of 80 mg/kg i.p. on postnatal day (P) 2 and randomized to INS, 0.3U twice daily from P3-P6 (STZ + INS group) or no treatment (STZ group). The acute effects on hippocampal neurochemical profile and transcript mRNA expression of insulin receptor (Insr), glucose transporters (Glut1, Glut 4 and Glut8) and poly(ADP-ribose)polymerase-1(Parp1, a marker of oxidative stress) were determined on P7 using in vivo 1H MR spectroscopy (MRS) and qPCR. The long-term effects on the neurochemical profile, microgliosis and synaptogenesis were determined at adulthood using 1H MRS and histochemical analysis. Relative to the control (CONT) group, mean blood glucose concentration was higher from P3 to P6 in the STZ and STZ+INS groups. On P7, MRS showed 10% higher taurine concentration in both STZ groups. qPCR showed 3-folds higher Insr and 5-folds higher Glut8 expression in the two STZ groups. Parp1 expression was 18% higher in the STZ group and normal in the STZ + INS group. At adulthood, blood glucose concentration in the fed state was higher in the STZ and STZ + INS groups. MRS showed 59% higher brain glucose concentration and histochemistry showed microgliosis in the hippocampal subareas in the STZ group. Brain glucose was normal in the STZ + INS group. Compared with the STZ group, phosphocreatine and phosphocreatine/creatine ratio were higher, and microglia in the hippocampal subareas fewer in the STZ + INS group (p < 0.05 for all). Neonatal hyperglycemia was associated with abnormal glucose metabolism and microgliosis in the adult hippocampus. INS administration during hyperglycemia attenuated these adverse effects and improved energy metabolism in the hippocampus.

show abstract

Section: Discussionmentioning

confidence: 99%

Intranasal Insulin Attenuates the Long-Term Adverse Effects of Neonatal Hyperglycemia on the Hippocampus in Rats

et al. 2022

View full text Add to dashboard Cite

show abstract

“…In this context, insulin plays a crucial role in the development of neuronal complexity, as well as in neurogenesis in early neonatal development. In this sense, insulin deprivation during early life may result in reduced neural network development, whereas exogenous administration of insulin may promote increased neural development and complexity [ 107 , 121 ]. A more complex neural network is a protective factor against the development of dementia [ 122 ].…”

Section: Link Between Diabetes Mellitus Alzheimer’s Disease and Vascu...mentioning

confidence: 99%

Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer’s Disease

Mohamed-Mohamed,

García-Morales,

Sánchez Lara

et al. 2023

Neurology International

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2D) is a metabolic disease reaching pandemic levels worldwide. In parallel, Alzheimer’s disease (AD) and vascular dementia (VaD) are the two leading causes of dementia in an increasingly long-living Western society. Numerous epidemiological studies support the role of T2D as a risk factor for the development of dementia. However, few basic science studies have focused on the possible mechanisms involved in this relationship. On the other hand, this review of the literature also aims to explore the relationship between T2D, AD and VaD. The data found show that there are several alterations in the central nervous system that may be promoting the development of T2D. In addition, there are some mechanisms by which T2D may contribute to the development of neurodegenerative diseases such as AD or VaD.

show abstract

“…Growth retardation, inflammation, malnutrition in pregnancy, infancy, and childhood are associated with the increased risk of cardiovascular diseases, hypertension, stroke, type 2 diabetes, and neurodegenerative disorders [ 131 , 132 , 133 , 134 ]. This phenomenon was termed as Developmental Origin of Health and Disease (DOHAD) hypothesis [ 135 ].…”

Section: Polyploidy Meets the Hallmarks Of Developmental Programming ...mentioning

confidence: 99%

“…Excessive polyploidization can be associated with the diseases that usually originated from the developmental programming, including cardiovascular disease, hypertension, neurodegenerative disease, type 2 diabetes, metabolic syndrome, and others [ 9 , 74 , 77 , 131 , 132 , 133 , 134 ].…”

Section: Polyploidy Meets the Hallmarks Of Developmental Programming ...mentioning

confidence: 99%

Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases

Anatskaya

Vinogradov

2022

IJMS

View full text Add to dashboard Cite

DNA replication during cell proliferation is ‘vertical’ copying, which reproduces an initial amount of genetic information. Polyploidy, which results from whole-genome duplication, is a fundamental complement to vertical copying. Both organismal and cell polyploidy can emerge via premature cell cycle exit or via cell-cell fusion, the latter giving rise to polyploid hybrid organisms and epigenetic hybrids of somatic cells. Polyploidy-related increase in biological plasticity, adaptation, and stress resistance manifests in evolution, development, regeneration, aging, oncogenesis, and cardiovascular diseases. Despite the prevalence in nature and importance for medicine, agri- and aquaculture, biological processes and epigenetic mechanisms underlying these fundamental features largely remain unknown. The evolutionarily conserved features of polyploidy include activation of transcription, response to stress, DNA damage and hypoxia, and induction of programs of morphogenesis, unicellularity, and longevity, suggesting that these common features confer adaptive plasticity, viability, and stress resistance to polyploid cells and organisms. By increasing cell viability, polyploidization can provide survival under stressful conditions where diploid cells cannot survive. However, in somatic cells it occurs at the expense of specific function, thus promoting developmental programming of adult cardiovascular diseases and increasing the risk of cancer. Notably, genes arising via evolutionary polyploidization are heavily involved in cancer and other diseases. Ploidy-related changes of gene expression presumably originate from chromatin modifications and the derepression of bivalent genes. The provided evidence elucidates the role of polyploidy in evolution, development, aging, and carcinogenesis, and may contribute to the development of new strategies for promoting regeneration and preventing cardiovascular diseases and cancer.

show abstract

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

Cited by 3 publications

References 47 publications

Intranasal Insulin Attenuates the Long-Term Adverse Effects of Neonatal Hyperglycemia on the Hippocampus in Rats

Intranasal Insulin Attenuates the Long-Term Adverse Effects of Neonatal Hyperglycemia on the Hippocampus in Rats

Physiological Mechanisms Inherent to Diabetes Involved in the Development of Dementia: Alzheimer’s Disease

Polyploidy as a Fundamental Phenomenon in Evolution, Development, Adaptation and Diseases

Contact Info

Product

Resources

About