Chromium picolinate attenuates cognitive deficit in ICV-STZ rat paradigm of sporadic Alzheimer’s-like dementia via targeting neuroinflammatory and IRS-1/PI3K/AKT/GSK-3β pathway

Akhtar, Ansab; Dhaliwal, Jatinder; Saroj, Priyanka; Uniyal, Ankit; Bishnoi, Mahendra; Sah, Sangeeta Pilkhwal

doi:10.1007/s10787-019-00681-7

Cited by 51 publications

(40 citation statements)

References 60 publications

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“…These were in turn found to be involved in triggering secondary signaling pathways through GRIN2B, which is associated with cocaine addiction, cognitive central hypoventilation syndrome and eating disorders. A number of research studies have reported downregulation of BDNF expression, which is in line with our findings (Kang et al 2020 ; Akhtar et al 2020 ).…”

Section: Discussionsupporting

confidence: 92%

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

2021

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Alzheimer’s disease (AD), a dreadful neurodegenerative disorder that affects cognitive and behavioral function in geriatric populations, is characterized by the presence of amyloid deposits and neurofibrillary tangles in brain regions. The International D World Alzheimer Report 2018 noted a global prevalence of 50 million AD cases and forecasted a threefold rise to 139 million by 2050. Although there exist numerous genetic association studies pertinent to AD in different ethnicities, critical genetic factors and signaling pathways underlying its pathogenesis remain ambiguous. This study was aimed to analyze the genetic data retrieved from 32 Gene Expression Omnibus datasets belonging to diverse ethnic cohorts in order to identify overlapping differentially expressed genes (DEGs). Stringent selection criteria were framed to shortlist appropriate datasets based on false discovery rate (FDR) p -value and log FC, and relevant details of upregulated and downregulated DEGs were retrieved. Among the 32 datasets, only six satisfied the selection criteria. The GEO2R tool was employed to retrieve significant DEGs. Nine common DEGs, i.e., SLC5A3 , BDNF , SST , SERPINA3 , RTN3 , RGS4 , NPTX , ENC1 and CRYM were found in more than 60% of the selected datasets. These DEGs were later subjected to protein–protein interaction analysis with 18 AD-specific literature-derived genes. Among the nine common DEGs, BDNF , SST , SERPINA3 , RTN3 and RGS4 exhibited significant interactions with crucial proteins including BACE1, GRIN2B, APP, APOE, COMT, PSEN1, INS, NEP and MAPT. Functional enrichment analysis revealed involvement of these genes in trans-synaptic signaling, chemical transmission, PI3K pathway signaling, receptor–ligand activity and G protein signaling. These processes are interlinked with AD pathways.

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Section: Discussionsupporting

confidence: 92%

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

2021

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“…Insulin shows neuromodulatory actions in the brain and insulin signaling is involved in neuronal plasticity, gene expression, energy production, and neuronal survival [ 8 ]. Insulin signaling impairment and brain insulin resistance may lead to impaired memory and cognitive dysfunction in AD [ 8 , 9 ]. Therefore, to attenuate the locomotor and cognitive deficits caused by brain insulin resistance in AD might be one of the key treatments for AD.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, Magnolol can mitigate neuroinflammation and oxidative stress in mice with prefrontal cortex [ 25 ], and it also has the ability to mitigate oxidative stress in adipocytes [ 21 ]. In addition, a recent research has proved that Magnolol can attenuate inflammation in the mice model of formalin-induced inflammatory pain and has no deteriorating effect on their locomotor and cognitive abilities [ 9 ]. However, there is still no clue about the effect of Magnolol on the neuroinflammation, locomotor impairment, and cognitive deficit caused by AD.…”

Section: Introductionmentioning

confidence: 99%

Magnolol attenuates the locomotor impairment, cognitive deficit, and neuroinflammation in Alzheimer’s disease mice with brain insulin resistance via up-regulating miR-200c

Chen

Liu

et al. 2021

Bioengineered

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In this study, we aimed to investigate the effect of Magnolol on Alzheimer’s disease (AD). After the model of streptozotocin-induced AD mice with brain insulin resistance was established, the mice were treated with Magnolol or miR-200c antagomiR. The abilities of ambulations, rearings, discrimination, spatial learning, and memory were evaluated by open-field test (OFT), novel object recognition (NOR), and morris water maze (MWM) tests. The levels of malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), and miR-200c in the mice hippocampus were evaluated by enzyme-linked immunosorbent assay, Western blot, or Quantitative real-time Polymerase Chain Reaction. In AD mice model, streptozotocin induced the locomotor impairment and cognitive deficit, up-regulated levels of MDA, TNF-α, IL-6, and CRP, while down-regulated levels of GSH, SOD, and miR-200c. Magnolol increased the rearings numbers and discrimination index of AD mice in OFT and NOR tests. Magnolol increased the number of entries in the target quadrant and time spent in the target quadrant and decreased the escape latency of AD mice in the MWM test. Magnolol also down-regulated the levels of MDA, TNF-α, IL-6, and CRP, and up-regulated the levels of GSH, SOD, and miR-200c in the hippocampus tissues of AD mice. However, miR-200c antagomiR did the opposite and further offset the effects of the Magnolol on AD mice. Magnolol attenuated the locomotor impairment, cognitive deficit, and neuroinflammatory in AD mice with brain insulin resistance via up-regulating miR-200c.

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“…The chloral hydrate (350 mg/kg，Kelun, Tianjin, China) was used to anesthetize rats, which were placed on a stereotactic device (Kiel, Wl) for the administration of unilateral ventricular injection of chloral hydrate (5 μL per side), the dose was repeated after 48‐hr interval. The sham group of rats was injected with artificial cerebrospinal fluid, and rats in the other group were injected with 60 μg/μl STZ (A. Akhtar et al, 2020) (STZ was purchased from Sigma, purity≥98%). Injection site coordinates: anterior fontanelle as origin, backward 0.8–1.0 mm; lateral, 1.2–1.5 mm from left and right side of the sagittal seam; depth, 3.1–3.5 mm from the skull.…”

Section: Methodsmentioning

confidence: 99%

Acteoside‐improved streptozotocin‐induced learning and memory impairment by upregulating hippocampal insulin, glucose transport, and energy metabolism

Chen

Gao

Zhang

et al. 2020

Phytotherapy Research

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Alzheimer's disease (AD), a neurodegenerative disease, has been, by and large, correlated to insulin pathway, glucose level, and energy metabolism in the brain. Intracerebroventricular administration of streptozotocin (ICV‐STZ) leads to glucose and energy metabolism dysfunction, cognitive impairment, and increased oxidative stress in the brain. Acteoside has a myriad of pharmacological effects on the brain, namely, neuroprotection and recuperation of cognitive functions. The primary focus of the current study was to examine the effect of acteoside on insulin, glucose transport, and energy metabolism in the hippocampal area of the brain. The behavioral experiments such as spatial memory, active learning, and passive memory suggested that acetoside ameliorated the ICV‐STZ‐induced learning and cognitive impairment. The acteoside induced increase in the protein expression of glucose transporters (Glu T1, Glu T3, and Glu T4), glucose, and insulin levels in the hippocampus for maintaining normal learning and memory function were demonstrated by Western blot. In addition, acteoside's long‐term oral administration increased the the ratio of ATP content divided by ADP content (ATP/ADP) ratio, which, in turn, reduced the reactiveoxygen species (ROS) level and improved the cellular oxidative stress response. Compared with the model group, the above results show significant differences in different degrees (p < .05 or p < .01). This study suggests that acteoside can ameliorate the ICV‐STZ‐induced learning and memory impairment caused due to insulin receptor, insulin receptor substrate 1, Glu T1, Glu T3, and Glu T4 pathways by triggering intracerebral metabolism.

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Chromium picolinate attenuates cognitive deficit in ICV-STZ rat paradigm of sporadic Alzheimer’s-like dementia via targeting neuroinflammatory and IRS-1/PI3K/AKT/GSK-3β pathway

Cited by 51 publications

References 60 publications

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

Revelation of Pivotal Genes Pertinent to Alzheimer’s Pathogenesis: A Methodical Evaluation of 32 GEO Datasets

Magnolol attenuates the locomotor impairment, cognitive deficit, and neuroinflammation in Alzheimer’s disease mice with brain insulin resistance via up-regulating miR-200c

Acteoside‐improved streptozotocin‐induced learning and memory impairment by upregulating hippocampal insulin, glucose transport, and energy metabolism

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