Animal model of dementia induced by entorhinal synaptic damage and partial restoration of cognitive deficits by BDNF and carnitine

• Published in: Journal of neuroscience research 2002-11, Vol.70 (3), p.519-527
• Main Authors: Ando, Susumu, Kobayashi, Satoru, Waki, Hatsue, Kon, Kazuo, Fukui, Fumiko, Tadenuma, Tomoko, Iwamoto, Machiko, Takeda, Yasuo, Izumiyama, Naotaka, Watanabe, Kazutada, Nakamura, Hiroaki
• Format: Article
• Language: English
• Subjects: Aging - metabolism; Alzheimer Disease - drug therapy; Alzheimer Disease - pathology; Alzheimer Disease - physiopathology; Animals; BDNF; botulinum toxin; Botulinum Toxins, Type A - pharmacology; Brain-Derived Neurotrophic Factor - genetics; Brain-Derived Neurotrophic Factor - pharmacology; Brain-Derived Neurotrophic Factor - therapeutic use; carnitine; Carnitine - pharmacology; Carnitine - therapeutic use; Cognition Disorders - drug therapy; Cognition Disorders - pathology; Cognition Disorders - physiopathology; dementia model; Disease Models, Animal; entorhinal cortex; Entorhinal Cortex - drug effects; Entorhinal Cortex - pathology; Entorhinal Cortex - ultrastructure; Genetic Vectors - therapeutic use; learning; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Male; Maze Learning - drug effects; Maze Learning - physiology; Membrane Proteins - antagonists & inhibitors; Membrane Proteins - metabolism; memory; Microscopy, Electron; Nerve Regeneration - drug effects; Nerve Regeneration - physiology; Presynaptic Terminals - drug effects; Presynaptic Terminals - pathology; Presynaptic Terminals - ultrastructure; R-SNARE Proteins; Rats; Rats, Inbred F344; Recombinant Fusion Proteins - pharmacology; Recovery of Function - drug effects; Recovery of Function - physiology; synaptic plasticity
• ISSN: 0360-4012; 1097-4547
• DOI: 10.1002/jnr.10443

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.