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

Abstract

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.

CREB expression mediates amyloid β-induced basal BDNF downregulation

“…Our current findings reveal a novel mechanism of BDNF downregulation which could lead to new methods to combat BDNF decline in AD. Increasing BDNF levels has been shown to greatly improve learning and memory deficits in animal models (Ando et al, 2002;Blurton-Jones et al, 2009;Fahnestock et al, 2012;Nagahara et al, 2009Nagahara et al, , 2013. Furthermore, increasing CREB activity via viral delivery of CREB activators, CREB binding protein (Caccamo et al, 2010;Espana et al, 2010) and CREB-regulated transcription cofactor 1 (Espana et al, 2010), has successfully reversed synaptic atrophy and learning and memory impairments in transgenic mice.…”

Physical Exercise Reverses Cognitive Impairment in Rats Subjected to Experimental Hyperprolinemia

“…Pro ? Exe proline plus exercise traumatic injury [50], dementia [51] and Alzheimer's disease [52], the finding that a short and moderate exercise protocol is sufficient to enhance learning and memory suggests that exercise might be an accessible form of intervention that could be used in conjunction with standard care measures for hyperprolinemic patients [53].…”

Association Analysis of Brain-Derived Neurotrophic Factor Val66Met Polymorphisms with Alzheimer’s Disease and Age of Onset

“…Although our finding does not provide evidence supporting the hypothesized relationships for the BDNF genetic variant and either AD susceptibility or onset age, we do not know whether this BDNF Val66Met polymorphism has effects on AD manifestations. For example, recent studies suggested that BDNF may play an important role in the pathogenesis of depression [11,12], a common comorbidity in AD patients, and BDNF could be a potential therapeutic agent for patients with AD [13,14]. It may be of interest to test the association for individual genetic variants of BDNF and the clinical symptoms of, and treatment response for, AD.…”