Lamotrigine attenuates deficits in synaptic plasticity and accumulation of amyloid plaques in APP/PS1 transgenic mice

Zhang, Maoying; Zheng, Chuanyi; Zou, Mingming; Zhu, Jian-Wei; Zhang, Yan; Wang, Jing; Liu, Chun‐Feng; Li, Qifa; Xiao, Zhi‐Cheng; Li, Shao; Ma, Quanhong; Xu, Ran

doi:10.1016/j.neurobiolaging.2014.06.009

Cited by 79 publications

(60 citation statements)

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“…It is notable that two other AEDs, levetiracetam and lamotrigine, have previously been found to ameliorate synaptic and cognitive deficits in a transgenic mouse model of AD, human amyloid precursor protein, and also in presenilin-1 mice (17,18).…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have suggested decreased neurogenesis in neurodegenerative and neurological disorders, such as Parkinson disease, Alzheimer disease (AD), Huntington disease, depression, epilepsy, schizophrenia, and other age-related disorders (2, 6 -14). Early onset of AD is characterized by the accumulation of amyloid-␤ (A␤) peptides, hippocampal hyperactivity, and alteration in neuronal networks, leading to increased incidence of epileptic seizures and cognitive and synaptic deficits in patients (15)(16)(17)(18). Antiepileptic drugs (AEDs) like levetiracetam and lamotrigine are known to reduce overexcitation and synaptic and cognitive deficits in animal models of AD (15,18).…”

mentioning

confidence: 99%

“…Early onset of AD is characterized by the accumulation of amyloid-␤ (A␤) peptides, hippocampal hyperactivity, and alteration in neuronal networks, leading to increased incidence of epileptic seizures and cognitive and synaptic deficits in patients (15)(16)(17)(18). Antiepileptic drugs (AEDs) like levetiracetam and lamotrigine are known to reduce overexcitation and synaptic and cognitive deficits in animal models of AD (15,18). However, a possible role of AEDs in neurogenesis and associated functions has not been fully explored.…”

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confidence: 99%

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Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway

Tiwari

Seth

Agarwal

et al. 2015

Journal of Biological Chemistry

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Background: Neurogenesis, the process of generation of new neurons, is reduced in Alzheimer disease (AD). Results: Ethosuximide (ETH), an anticonvulsant drug, increased neurogenesis, reduced neurodegeneration, and reversed cognitive impairments in a rat model of AD-like phenotypes. Conclusion: ETH induces neurogenesis, thus reversing AD-like phenotypes. Significance: ETH could be used as a therapeutic molecule to enhance neurogenesis.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway

Tiwari

Seth

Agarwal

et al. 2015

Journal of Biological Chemistry

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“…1A, B) and cortex (Fig. 1C, D) of APP/PS1 transgenic mice at 8 months of age, when the mice display AD-like pathology, such as high load of amyloid plaques, loss of dendritic spines and deficits in learning and memory (Zhang et al, 2014). In contrast, DISC1 exhibited identical levels in the hippocampus (Fig.…”

Section: Decreased Levels Of Disc1 In the Brains Of App/ps1 Transgenimentioning

confidence: 92%

“…This test was performed as described (Zhang et al, 2014). Briefly, mice were trained for 7 consecutive days, 4 trials per day.…”

Section: Morris Watermentioning

confidence: 99%

Disrupted-in-Schizophrenia-1 Attenuates Amyloid-β Generation and Cognitive Deficits in APP/PS1 Transgenic Mice by Reduction of β-Site APP-Cleaving Enzyme 1 Levels

Deng

Dong

et al. 2015

Neuropsychopharmacol

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Disrupted-in-Schizophrenia-1 (DISC1) is a genetic risk factor for a wide range of major mental disorders, including schizophrenia, major depression, and bipolar disorders. Recent reports suggest a potential role of DISC1 in the pathogenesis of Alzheimer's disease (AD), by referring to an interaction between DISC1 and amyloid precursor protein (APP), and to an association of a single-nucleotide polymorphism in a DISC1 intron and late onset of AD. However, the function of DISC1 in AD remains unknown. In this study, decreased levels of DISC1 were observed in the cortex and hippocampus of 8-month-old APP/PS1 transgenic mice, an animal model of AD. Overexpression of DISC1 reduced, whereas knockdown of DISC1 increased protein levels, but not mRNA levels of β-site APP-Cleaving Enzyme 1 (BACE1), a key enzyme in amyloid-β (Aβ) generation. Reduction of BACE1 protein levels by overexpression of DISC1 was accompanied by an accelerating decline rate of BACE1, and was blocked by the lysosomal inhibitor chloroquine, rather than proteasome inhibitor MG-132. Moreover, overexpression of DISC1 in the hippocampus with an adeno-associated virus reduced the levels of BACE1, soluble Aβ40/42, amyloid plaque density, and rescued cognitive deficits of APP/PS1 transgenic mice. These results indicate that DISC1 attenuates Aβ generation and cognitive deficits of APP/PS1 transgenic mice through promoting lysosomal degradation of BACE1. Our findings provide new insights into the role of DISC1 in AD pathogenesis and link a potential function of DISC1 to the psychiatric symptoms of AD.

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AQP4 Aggravates Cognitive Impairment in Sepsis‐Associated Encephalopathy through Inhibiting Na_v1.6‐Mediated Astrocyte Autophagy

et al. 2023

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The pathology of sepsis‐associated encephalopathy (SAE) is related to astrocyte‐inflammation associated with aquaporin‐4 (AQP4). The aim here is to investigate the effects of AQP4 associated with SAE and reveal its underlying mechanism causing cognitive impairment. The in vivo experimental results reveal that AQP4 in peripheral blood of patients with SAE is up‐regulated, also the cortical and hippocampal tissue of cecal ligation and perforation (CLP) mouse brain has significant rise in AQP4. Furthermore, the data suggest that AQP4 deletion could attenuate learning and memory impairment, attributing to activation of astrocytic autophagy, inactivation of astrocyte and downregulate the expression of proinflammatory cytokines induced by CLP or lipopolysaccharide (LPS). Furthermore, the activation effect of AQP4 knockout on CLP or LPS‐induced PPAR‐γ inhibiting in astrocyte is related to intracellular Ca2+ level and sodium channel activity. Learning and memory impairment in SAE mouse model are attenuated by AQP4 knockout through activating autophagy, inhibiting neuroinflammation leading to neuroprotection via down‐regulation of Nav1.6 channels in the astrocytes. This results in the reduction of Ca2+ accumulation in the cell cytosol furthermore activating the inhibition of PPAR‐γ signal transduction pathway in astrocytes.

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Lamotrigine attenuates deficits in synaptic plasticity and accumulation of amyloid plaques in APP/PS1 transgenic mice

Cited by 79 publications

References 65 publications

Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway

Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway

Disrupted-in-Schizophrenia-1 Attenuates Amyloid-β Generation and Cognitive Deficits in APP/PS1 Transgenic Mice by Reduction of β-Site APP-Cleaving Enzyme 1 Levels

AQP4 Aggravates Cognitive Impairment in Sepsis‐Associated Encephalopathy through Inhibiting Na_v1.6‐Mediated Astrocyte Autophagy

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Lamotrigine attenuates deficits in synaptic plasticity and accumulation of amyloid plaques in APP/PS1 transgenic mice

Cited by 79 publications

References 65 publications

Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway

Ethosuximide Induces Hippocampal Neurogenesis and Reverses Cognitive Deficits in an Amyloid-β Toxin-induced Alzheimer Rat Model via the Phosphatidylinositol 3-Kinase (PI3K)/Akt/Wnt/β-Catenin Pathway

Disrupted-in-Schizophrenia-1 Attenuates Amyloid-β Generation and Cognitive Deficits in APP/PS1 Transgenic Mice by Reduction of β-Site APP-Cleaving Enzyme 1 Levels

AQP4 Aggravates Cognitive Impairment in Sepsis‐Associated Encephalopathy through Inhibiting Nav1.6‐Mediated Astrocyte Autophagy

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AQP4 Aggravates Cognitive Impairment in Sepsis‐Associated Encephalopathy through Inhibiting Na_v1.6‐Mediated Astrocyte Autophagy