Premium
Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine
Author(s) -
Ando Susumu,
Kobayashi Satoru,
Waki Hatsue,
Kon Kazuo,
Fukui Fumiko,
Tadenuma Tomoko,
Iwamoto Machiko,
Takeda Yasuo,
Izumiyama Naotaka,
Watanabe Kazutada,
Nakamura Hiroaki
Publication year - 2002
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.10443
Subject(s) - neuroscience , entorhinal cortex , synaptic plasticity , morris water navigation task , t maze , psychology , water maze , spontaneous alternation , lesion , hippocampus , cognition , medicine , psychiatry , receptor
A rat dementia model with cognitive deficits was generated by synapse‐specific lesions using botulinum neurotoxin (BoNTx) type B in the entorhinal cortex. To detect cognitive deficits, different tasks were needed depending upon the age of the model animals. Impaired learning and memory with lesions were observed in adult rats using the Hebb‐Williams maze, AKON‐1 maze and a continuous alternation task in T‐maze. Cognitive deficits in lesioned aged rats were detected by a continuous alternation and delayed non‐matching‐to‐sample tasks in T‐maze. Adenovirus‐mediated BDNF gene expression enhanced neuronal plasticity, as revealed by behavioral tests and LTP formation. Chronic administration of carnitine over time pre‐ and post‐lesions seemed to partially ameliorate the cognitive deficits caused by the synaptic lesion. The carnitine‐accelerated recovery from synaptic damage was observed by electron microscopy. These results demonstrate that the BoNTx‐lesioned rat can be used as a model for dementia and that cognitive deficits can be alleviated in part by BDNF gene transfer or carnitine administration. © 2002 Wiley‐Liss, Inc.