Insulin potentiates the therapeutic effect of memantine against central STZ-induced spatial learning and memory deficit

Bahramian, Abbas; Rastegar, Karim; Namavar, Mohammad Reza; Moosavi, Maryam

doi:10.1016/j.bbr.2016.05.046

Cited by 11 publications

(2 citation statements)

References 33 publications

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“…The GSK-3β activation plays a central role in several pathologic hallmarks of AD such as memory impairment, hyperphosphorylation of tau, inflammatory responses and neuronal death (Hooper et al, 2008;Gabbouj et al, 2019). GSK inhibitors (Sayas and Ávila, 2021) or Akt activators (Bahramian et al, 2016;Yi et al, 2018) were found to exert protective effects in animal models of AD. While hippocampal Akt/GSK-3β is attenuated by memory deteriorative agents (Hooshmandi et al, 2018;Esmaili et al, 2021a), several memory enhancers were found to activate Akt/GSK-3β pathways within the hippocampus (SoukhakLari et al, 2018a;Kazerouni et al, 2020), which suggests the possible role of this pathway in learning and memory.…”

Section: Introductionmentioning

confidence: 99%

The effects of subchronic agmatine on passive avoidance memory, anxiety-like behavior and hippocampal Akt/GSK-3β in mice

Ostovan

Amiri

Moezi

et al. 2021

Behavioural Pharmacology

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Agmatine, a polyamine derived from l-arginine, has been suggested to modulate memory. However, the available evidence regarding the effect of agmatine on the memory of intact animals is contradictory. This study aimed to assess the dose–response effect of subchronic agmatine on passive avoidance memory and anxiety-like parameters of elevated plus maze in adult intact mice. Furthermore, considering the roles of Akt/GSK-3β signaling pathway in memory and Alzheimer’s disease, the hippocampal contents of phosphorylated and total forms of Akt and GSK-3β proteins were determined using the western blot technique. Agmatine was administered intraperitoneally at the doses of 10, 20, 30, 40 and 80 mg/kg/daily to adult male NMRI mice for 10 days after which the behavioral assessments were performed. Upon completion of the passive avoidance test, the hippocampi were removed for western blot analysis to detect the phosphorylated and total levels of Akt and GSK-3β proteins. Results showed the biphasic effect of agmatine on passive avoidance memory; in lower doses (10, 20 and 30 mg/kg), agmatine impaired memory whereas in higher ones (40 and 80 mg/kg) improved it. Though, agmatine in none of the doses affected animals’ anxiety-like parameters in an elevated plus maze. Moreover, the memory-improving doses of agmatine augmented Akt/GSK-3β pathway. This study showed the biphasic effect of agmatine on passive avoidance memory and an augmentation of hippocampal Akt/GSK-3β signaling pathway following the memory-improving doses of this polyamine.

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Section: Introductionmentioning

confidence: 99%

The effects of subchronic agmatine on passive avoidance memory, anxiety-like behavior and hippocampal Akt/GSK-3β in mice

Ostovan

Amiri

Moezi

et al. 2021

Behavioural Pharmacology

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“…This injection cannula was designed to extend at least 0.5 mm below the tip of the guide cannula and this cannula was left in place for additional 5 min to minimize the backflow of the drug. Microinjection of a single dose (15 µg/ 3µl) of LPS (L2882, Sigma) or its solvent (saline) was performed right after the surgery (day 0), and ICV administration of 3 mU insulin (based on a previous study (Bahramian et al, 2016[ 3 ])) or its vehicle (saline) (1 µl/day ICV) were done at exactly six days after surgery (days 1-6). These microinjections were administered at a constant speed of 0.5 µl/min.…”

Section: Methodsmentioning

confidence: 99%

Investigating the role of P38, JNK and ERK in LPS induced hippocampal insulin resistance and spatial memory impairment: effects of insulin treatment

Iloun

Abbasnejad

Janahmadi

et al. 2018

EXCLI Journal; 17:Doc825; ISSN 1611-2156

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Peripheral and Central Effects of Memantine in a Mixed Preclinical Mice Model of Obesity and Familial Alzheimer’s Disease

et al. 2018

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There is growing evidence that obesity associated with type 2 diabetes mellitus (T2DM) and aging are risk factors for the development of Alzheimer's disease (AD). However, the molecular mechanisms through which obesity interacts with β-amyloid (Aβ) to promote cognitive decline remains poorly understood. Memantine (MEM), a N-methyl-D-aspartate receptor antagonist, is currently used for the treatment of AD. Nonetheless, few studies have reported its effects on genetic preclinical models of this neurodegenerative disease exacerbated with high-fat diet (HFD)-induced obesity. Therefore, the present research aims to elucidate the effects of MEM on familial AD HFD-induced insulin resistance and learning and memory impairment. Furthermore, it aspires to determine the possible underlying mechanisms that connect AD to T2DM. Wild type and APPswe/PS1dE9 mice were used in this study. The animals were fed with either chow or HFD until 6 months of age, and they were treated with MEM-supplemented water (30 mg/kg) during the last 12 weeks. Our study demonstrates that MEM improves the metabolic consequences produced by HFD in this model of familial AD. Behavioural assessments confirmed that the treatment also improves animals learning abilities and decreases memory loss. Moreover, MEM treatment improves brain insulin signalling upregulating AKT, as well as cyclic adenosine monophosphate response element binding (CREB) expression, and modulates the amyloidogenic pathway, which, in turn, reduced the accumulation of Aβ. Moreover, this drug increases the activation of molecules involved with insulin signalling in the liver, such as insulin receptor substrate 2 (IRS2), which is a key protein regulating hepatic resistance to insulin. These results provide new insight into the role of MEM not only in the occurrence of AD treatment, but also in its potential application on peripheral metabolic disorders where Aβ plays a key role, as is the case of T2DM.

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Insulin potentiates the therapeutic effect of memantine against central STZ-induced spatial learning and memory deficit

Cited by 11 publications

References 33 publications

The effects of subchronic agmatine on passive avoidance memory, anxiety-like behavior and hippocampal Akt/GSK-3β in mice

The effects of subchronic agmatine on passive avoidance memory, anxiety-like behavior and hippocampal Akt/GSK-3β in mice

Investigating the role of P38, JNK and ERK in LPS induced hippocampal insulin resistance and spatial memory impairment: effects of insulin treatment

Peripheral and Central Effects of Memantine in a Mixed Preclinical Mice Model of Obesity and Familial Alzheimer’s Disease

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