Dataset Information

Lamotrigine Reduces Inflammatory Response and Ameliorates Executive Function Deterioration in an Alzheimer's-Like Mouse Model.

ABSTRACT: Alzheimer's disease (AD) has been described in the literature, to be associated with impairment of executive function which develops early in the course of disease, and an effective treatment for this clinical feature remains elusive. Preclinical studies have implied that lamotrigine, an antiepileptic agent, could be a potential treatment for executive dysfunction in AD patients. Although there have been promising results in previous studies with lamotrigine, executive function has never been measured using animal models. The aim of the present study was to evaluate the effects of lamotrigine on executive function and determine whether lamotrigine can attenuate inflammatory response in an AD mouse model. Nontransgenic and transgenic mice were treated with lamotrigine (0 or 30?mg/kg/day) in a standard laboratory chow diet starting at 3 months of age. After 6 months of continuous lamotrigine administration, there was a marked improvement in executive function and a significant attenuation in the expression of proinflammatory cytokines. These results suggest that lamotrigine could ameliorate executive dysfunction and brain inflammatory response in the mouse model of AD and early lamotrigine intervention may be a promising therapeutic strategy for AD.

SUBMITTER: Wang K

PROVIDER: S-EPMC5155079 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Lamotrigine Reduces Inflammatory Response and Ameliorates Executive Function Deterioration in an Alzheimer's-Like Mouse Model.

Wang Kexin K Fernandez-Escobar Alejandro A Han Shuhong S Zhu Ping P Wang Jun-Hui JH Sun Yu Y

BioMed research international 20161130

Alzheimer's disease (AD) has been described in the literature, to be associated with impairment of executive function which develops early in the course of disease, and an effective treatment for this clinical feature remains elusive. Preclinical studies have implied that lamotrigine, an antiepileptic agent, could be a potential treatment for executive dysfunction in AD patients. Although there have been promising results in previous studies with lamotrigine, executive function has never been me ...[more]

PMID: 28042572

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Project description:BACKGROUND:Studies suggest a role of the innate immune system, including the activity of neutrophils, in neurodegeneration related to Alzheimer's disease (AD), but prospective cognitive data remain lacking in humans. We aimed to investigate the predictive relationship between neutrophil-associated inflammatory proteins in peripheral blood and changes in memory and executive function over 1?year in patients with AD. METHODS:Participants with AD were identified from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Neutrophil gelatinase-associated lipocalin (NGAL), myeloperoxidase (MPO), interleukin-8 (IL-8), macrophage inflammatory protein-1 beta (MIP-1?), and tumor necrosis factor (TNF) were assayed by luminex immunofluorescence multiplex assay at baseline. Confirmatory factor analysis was used to test an underlying neutrophil associated plasma inflammatory factor. Composite z-scores for memory and executive function were generated from multiple tests at baseline and at 1?year. A multiple linear regression model was used to investigate the association of the baseline inflammatory factor with changes in memory and executive function over 1?year. RESULTS:Among AD patients (n?=?109, age?=?74.8?±?8.1, 42% women, Mini Mental State Examination [MMSE]?=?23.6?±?1.9), the neutrophil-related inflammatory proteins NGAL (??=?0.595, p?<?.001), MPO (??=?0.575, p?<?.001), IL-8 (??=?0.525, p?<?.001), MIP-1? (??=?0.411, p?=?.008), and TNF (??=?0.475, p?<?.001) were found to inform an underlying factor. Over 1?year, this inflammatory factor predicted a decline in executive function (??=?-?0.152, p?=?0.015) but not memory (??=?0.030, p?=?0.577) in models controlling for demographics, brain atrophy, white matter hyperintensities, the ApoE ?4 allele, concomitant medications, and baseline cognitive performance. CONCLUSIONS:An inflammatory factor constructed from five neutrophil-related markers in peripheral blood predicted a decline in executive function over 1?year in people with mild AD.

Dataset Information

Lamotrigine Reduces Inflammatory Response and Ameliorates Executive Function Deterioration in an Alzheimer's-Like Mouse Model.

Publications

Lamotrigine Reduces Inflammatory Response and Ameliorates Executive Function Deterioration in an Alzheimer's-Like Mouse Model.

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