SUN11602 has basic fibroblast growth factor-like activity and attenuates neuronal damage and cognitive deficits in a rat model of Alzheimer׳s disease induced by amyloid β and excitatory amino acids
| Autor: | Nobuhiro Narii, Tetsushi Oka, Ryoko Ogino, Naohiro Takemoto, Sayaka Yoshida, Norihito Murayama, Nobuhiro Ueno, Takafumi Noshita, Teruyoshi Inoue, Tetsuya Toba |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Neurite Neuroscience(all) Basic fibroblast growth factor Clinical Neurology Spatial learning Water maze Phenylenediamines Hippocampal formation Pharmacology Hippocampus Neuroprotection chemistry.chemical_compound Cognition Alzheimer Disease Neurites medicine Animals Rats Wistar Ibotenic Acid Molecular Biology Amyloid beta-Peptides General Neuroscience Neurite outgrowth medicine.disease Peptide Fragments Rats Inbred F344 Rats Fibroblast Growth Factors Disease Models Animal Memory Short-Term Neuroprotective Agents SUN11602 bFGF chemistry Benzamides NMDA receptor Female Neurology (clinical) Alzheimer's disease Learning capacity Neuroscience Ibotenic acid Developmental Biology |
| Zdroj: | Brain Research. 1585:159-166 |
| ISSN: | 0006-8993 |
| DOI: | 10.1016/j.brainres.2014.08.023 |
| Popis: | Basic fibroblast growth factor (bFGF/FGF-2) is known to possess neuroprotective and neurite outgrowth activity properties. In this study, the effects of a novel synthetic compound that mimics the neuroprotective properties of bFGF – SUN11602 – were examined in vitro and in vivo. SUN11602 promoted neurite outgrowth of primarily cultured rat hippocampal neurons. For the in vivo study, an Alzheimer׳s disease (AD) model with severe damage to the hippocampal tissue was constructed by injecting the hippocampi of rats with aggregated Aβ1–40, followed 48h later by an injection of ibotenate [an agonist for N-methyl-d-aspartate (NMDA) receptor]. Oral administration of SUN11602 at the midpoint of Aβ1–40 and ibotenate injections attenuated short-term memory impairment in the Y-maze test, as well as spatial learning deficits in the water maze task. In addition, the SUN11602 treatment inhibited the increase of peripheral-type benzodiazepine-binding sites (PTBBS), which are a marker for gliosis. A negative correlation was found between PTBBS numbers and learning capacity in the water maze task. These results suggest that SUN111602 improved memory and learning deficits in the hippocampally lesioned rats by preventing neuronal death and/or promotion of neurite outgrowth. Taken together, these results indicate that SUN11602, a bFGF-like compound with neuroprotective and neurite outgrowth activity, may be beneficial for the treatment of progressive neurodegenerative diseases such as AD. |
| Databáze: | OpenAIRE |
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