title: 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.
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
authors.forename: Kexin
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Medicine, CES University, Medellin, Antioquia, Colombia.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Fernandez-Escobar
authors.affiliation: Department of Medicine, Division of Rheumatology & Clinical Immunology, University of Florida, Gainesville, FL 32610-0275, USA.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, FL 32610-0284, USA.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhu
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON, Canada M5S1A8.
authors.forename: Jun-Hui
authors.identifier: 0000-0003-4187-3441
authors.initials: JH
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
authors.forename: Yu
authors.identifier: 0000-0002-1286-1823
authors.initials: Y
authors.lastname: Sun
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000503:physiopathology*; D003072:Cognition Disorders; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077213:Lamotrigine; D051379:Mice; D008822:Mice, Transgenic; D014227:Triazines / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D014227:Triazines; D000077213:Lamotrigine