PMID- 25044076 OWN - NLM STAT- MEDLINE DCOM- 20151109 LR - 20181202 IS - 1558-1497 (Electronic) IS - 0197-4580 (Linking) VI - 35 IP - 12 DP - 2014 Dec TI - Lamotrigine attenuates deficits in synaptic plasticity and accumulation of amyloid plaques in APP/PS1 transgenic mice. PG - 2713-2725 LID - S0197-4580(14)00428-X [pii] LID - 10.1016/j.neurobiolaging.2014.06.009 [doi] AB - Hyperactivity and its compensatory mechanisms may causally contribute to synaptic and cognitive deficits in Alzheimer's disease (AD). Blocking the overexcitation of the neural network, with levetiracetam (LEV), a sodium channel blocker applied in the treatment of epilepsy, prevented synaptic and cognitive deficits in human amyloid precursor protein (APP) transgenic mice. This study has brought the potential use of antiepileptic drugs (AEDs) in AD therapy. We showed that the chronic treatment with lamotrigine (LTG), a broad-spectrum AED, suppressed abnormal spike activity, prevented the loss of spines, synaptophysin immunoreactivity, and neurons, and thus attenuated the deficits in synaptic plasticity and learning and memory in APP and presenilin 1 (PS1) mice, which express human mutant APP and PS1. In contrast with LEV, which failed to reduce the generation of amyloid beta, the chronic LTG treatment reduced the cleavage of APP by beta-secretase and thus the numbers and the size of amyloid plaques in the brains of APP and PS1 mice. Moreover, the levels of brain-derived neurotrophic growth factor (BDNF) and nerve growth factor (NGF) were enhanced in the brains of APP and PS1 mice by the chronic LTG treatment. Therefore, these observations demonstrate that LTG attenuates AD pathology through multiple mechanisms, including modulation of abnormal network activity, reduction of the generation of amyloid beta and upregulation of BDNF and NGF. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Zhang, Mao-Ying AU - Zhang MY AD - Affiliated Bayi Brain Hospital, Beijing Military Hospital, PLA and PhD Student Program of Southern Medical University, Beijing, China. FAU - Zheng, Chuan-Yi AU - Zheng CY AD - Affiliated Bayi Brain Hospital, Beijing Military Hospital, PLA and PhD Student Program of Southern Medical University, Beijing, China. FAU - Zou, Ming-Ming AU - Zou MM AD - Affiliated Bayi Brain Hospital, Beijing Military Hospital, PLA and PhD Student Program of Southern Medical University, Beijing, China. FAU - Zhu, Jian-Wei AU - Zhu JW AD - Affiliated Bayi Brain Hospital, Beijing Military Hospital, PLA and PhD Student Program of Southern Medical University, Beijing, China. FAU - Zhang, Yan AU - Zhang Y AD - Affiliated Bayi Brain Hospital, Beijing Military Hospital, PLA and PhD Student Program of Southern Medical University, Beijing, China. FAU - Wang, Jing AU - Wang J AD - Affiliated Bayi Brain Hospital, Beijing Military Hospital, PLA and PhD Student Program of Southern Medical University, Beijing, China. FAU - Liu, Chun-Feng AU - Liu CF AD - Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, Jiangsu Province, China. FAU - Li, Qi-Fa AU - Li QF AD - Department of Physiology, Dalian Medical University, Dalian, China. FAU - Xiao, Zhi-Cheng AU - Xiao ZC AD - Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia. FAU - Li, Shao AU - Li S AD - Department of Physiology, Dalian Medical University, Dalian, China. Electronic address: lishao89@hotmail.com. FAU - Ma, Quan-Hong AU - Ma QH AD - Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases, Institute of Neuroscience, Soochow University, Suzhou, Jiangsu Province, China. Electronic address: h999.judy@gmail.com. FAU - Xu, Ru-Xiang AU - Xu RX AD - Affiliated Bayi Brain Hospital, Beijing Military Hospital, PLA and PhD Student Program of Southern Medical University, Beijing, China. Electronic address: zjxuruxiang@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140616 PL - United States TA - Neurobiol Aging JT - Neurobiology of aging JID - 8100437 RN - 0 (Amyloid beta-Peptides) RN - 0 (Anticonvulsants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Triazines) RN - 9061-61-4 (Nerve Growth Factor) RN - U3H27498KS (Lamotrigine) SB - IM MH - Alzheimer Disease/drug therapy/metabolism/pathology/physiopathology MH - Amyloid beta-Peptides/*metabolism MH - Animals MH - Anticonvulsants/*pharmacology/*therapeutic use MH - Brain/*metabolism MH - Brain-Derived Neurotrophic Factor/metabolism MH - Disease Models, Animal MH - Down-Regulation/drug effects MH - Humans MH - Lamotrigine MH - Learning/drug effects MH - Memory/drug effects MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Nerve Growth Factor/metabolism MH - Neuronal Plasticity/*drug effects MH - Plaque, Amyloid/*metabolism MH - Triazines/*pharmacology/*therapeutic use MH - Up-Regulation/drug effects OTO - NOTNLM OT - Alzheimer's disease OT - Antiepileptic drug OT - Hyperexcitability OT - Lamotrigine OT - Synaptic plasticity EDAT- 2014/07/22 06:00 MHDA- 2015/11/10 06:00 CRDT- 2014/07/22 06:00 PHST- 2014/02/02 00:00 [received] PHST- 2014/06/06 00:00 [revised] PHST- 2014/06/10 00:00 [accepted] PHST- 2014/07/22 06:00 [entrez] PHST- 2014/07/22 06:00 [pubmed] PHST- 2015/11/10 06:00 [medline] AID - S0197-4580(14)00428-X [pii] AID - 10.1016/j.neurobiolaging.2014.06.009 [doi] PST - ppublish SO - Neurobiol Aging. 2014 Dec;35(12):2713-2725. doi: 10.1016/j.neurobiolaging.2014.06.009. Epub 2014 Jun 16.