A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia

Agrawal, Rahul; Tyagi, Ethika; Shukla, Rakesh; Nath, Chandishwar

doi:10.1016/j.neuropharm.2009.01.005

Cited by 145 publications

(88 citation statements)

References 43 publications

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“…In accordance with this notion, it has been reported in icv STZ rats' decrease in insulin gene, IR protein and hyperphosphorylated tau protein in the hippocampus and cortex [31], and decrease in IR expression and key proteins of the insulin signaling cascade (e.g. phosphorylation of IRS-1 and Akt) in the CA3 hippocampal region associated with memory damage [45]. Furthermore, the treatment with an insulin sensitizer (e.g., pioglitazone) reversed memory deficit in icv STZ rats [30] [38].…”

Section: Discussionsupporting

confidence: 55%

Role of GSK3<i>β</i> and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease

Ponce-López¹,

Hong²,

Abascal-Díaz³

et al. 2017

AAD

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Intracerebroventricular administration (ICV) of streptozotocin (STZ) in rats has been associated to desensitization of the insulin receptor (IR) and biochemical changes similar to those occurring in Alzheimer's disease (AD) or older brains, so it has been proposed as a suitable model for studying some of the pathological features of AD sporadic type (SAD). In this study, we investigated the role of glycogen synthase kinase 3β (GSK3β) and protein phosphatase 2A (PP2A) in the regulation of the phosphorylation of tau (p-tau). Results showed that ICV-STZ treated rats had deficits in short-(1.5-h) and long-term (24-and 48-h) memory after one month of ICV-STZ treatment and six months relative to control rats. The memory deficit was associated to increasing [F(3, 12) = 31.48, p < 0.0001] p-tau in the hippocampus but not in prefrontal cortex (PFC). Likewise, STZ reduced phosphorylation of GSK3β (p-GSK3β) and PP2A in hippocampus and PFC, indicating that GSK3β and PP2A contributed to regulation of p-tau. These data supporting the model with ICV-STZ in rat are adequate to study the progressive memory impairment associated to hyperphosphorylation of tau and the cascade of insulin receptor signaling; confirm that phosphatidyl-inositol-3 kinase-protein kinase B (PI3K-PKB/Akt-GSK3β) and PP2A are involved in the modulation of proteins responsible for the regulation of neurodegeneration in AD.

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Section: Discussionsupporting

confidence: 55%

Role of GSK3<i>β</i> and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease

Ponce-López¹,

Hong²,

Abascal-Díaz³

et al. 2017

AAD

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“…LX2343 ameliorated learning and memory impairments in ICV-STZ rats ICV injection of rats with a sub-diabetogenic dose of STV has been shown to be closely linked to the sporadic dementia of Alzheimer's disease [34] , which is characterized by cognitive impairment [35] , OS [35] , impaired glucose metabolism [36] , and hyperphosphorylated tau [37] . Given the pathological features of ICV-STZ rats and the efficiency of LX2343 in both protecting neuronal cells and attenuating tau pathology, we performed the MWM assay to examine the potential of LX2343 in the amelioration of memory impairment in ICV-STZ rats.…”

Section: Wwwchinapharcom Guo Xd Et Almentioning

confidence: 99%

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

et al. 2017

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alzheimer's disease (aD) is a progressive neurodegenerative disease leading to the irreversible loss of brain neurons and cognitive abilities, and the vicious interplay between oxidative stress (OS) and tauopathy is believed to be one of the major players in aD development. Here, we demonstrated the capability of the small molecule N-(1,3-benzodioxol-5-yl)-2-[5-chloro-2-methoxy(phenylsulfonyl)anilino]acetamide (LX2343) to ameliorate the cognitive dysfunction of aD model rats by inhibiting OS-induced neuronal apoptosis and tauopathy. Streptozotocin (STZ) was used to induce OS in neuronal cells in vitro and in aD model rats that were made by intracerebroventricular injection of STZ (3 mg/kg, bilaterally), and Morris water maze test was used to evaluate the cognitive dysfunction in ICV-STZ rats. Treatment with LX2343 (5-20 μmol/L) significantly attenuated STZ-induced apoptosis in SH-SY5Y cells and mouse primary cortical neurons by alleviating OS and inhibiting the JNK/p38 and pro-apoptotic pathways. LX2343 was able to restore the integrity of mitochondrial function and morphology, increase aTP biosynthesis, and reduce ROS accumulation in the neuronal cells. In addition, LX2343 was found to be a non-ATP competitive GSK-3β inhibitor with IC 50 of 1.84±0.07 μmol/L, and it potently inhibited tau hyperphosphorylation in the neuronal cells. In ICV-STZ rats, administration of LX2343 (7, 21 mg·kg -1 ·d -1 , ip, for 5 weeks) efficiently improved their cognitive deficits. LX2343 ameliorates the cognitive dysfunction in the AD model rats by suppressing OS-induced neuronal apoptosis and tauopathy, thus highlighting the potential of LX2343 for the treatment of aD.

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“…Melatonin can improve insulin resistance via alteration of pancreatic gene expression in male mice (195). In the rat brain, insulin receptors that are involved in memory respond to melatonin (196).…”

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confidence: 99%

Effects of Melatonin on Nervous System Aging: Neurogenesis and Neurodegeneration

et al. 2013

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Abstract. Neural aging as a progressive loss of function involves central and peripheral postmitotic neurons and neural stem cells (NSCs). It promotes neurodegeneration, impairs neurogenesis, and can be considered a cause of cognitive impairment and sensory and motor deficits in the elderly. Age-related morphological atrophic changes and cellular alterations are addressed by neural aging mechanisms. Neurogenesis declines during aging through several mechanisms such as an increase in quiescence state, changes in lineage fate, telomerase dysfunction, the failure of the DNA repair system, increased apoptosis, and the impairment of self-renewal. The selfrenewal transcriptional factor Sox2 has been correlated with retrotransposon L1 and certain cellcycle-and epigenetic-related factors, which are sometimes considered age-related factors in NSC aging. As neurogenesis decreases, non-mitotic neurons undergo neurodegeneration by oxidative stress, sirtuin, insulin signaling and mTOR alteration, mitochondrial dysfunction, and protein misfolding and aggregation. As neurodegeneration and impaired neurogenesis promote the nervous system aging process, the identification of neuronal anti-aging is required to raise life expectancy. The role of melatonin in increasing neurogenesis and protecting against neurodegeneration has been investigated. Here, we review nervous system aging that is correlated with mechanisms of neurodegeneration and the impairment of neurogenesis and evaluate the effects of melatonin on these processes.

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A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia

Cited by 145 publications

References 43 publications

Role of GSK3<i>β</i> and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease

Role of GSK3<i>β</i> and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

Effects of Melatonin on Nervous System Aging: Neurogenesis and Neurodegeneration

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A study of brain insulin receptors, AChE activity and oxidative stress in rat model of ICV STZ induced dementia

Cited by 145 publications

References 43 publications

Role of GSK3&lt;i&gt;β&lt;/i&gt; and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease

Role of GSK3&lt;i&gt;β&lt;/i&gt; and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease

LX2343 alleviates cognitive impairments in AD model rats by inhibiting oxidative stress-induced neuronal apoptosis and tauopathy

Effects of Melatonin on Nervous System Aging: Neurogenesis and Neurodegeneration

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Product

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Role of GSK3<i>β</i> and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease

Role of GSK3<i>β</i> and PP2A on Regulation of Tau Phosphorylation in Hippocampus and Memory Impairment in ICV-STZ Animal Model of Alzheimer’s Disease