Microtubule Dynamicity Is More Important than Stability in Memory Formation: an In Vivo Study.
It has been shown that microtubule (MT) activity and dynamics can have huge impacts on synaptic plasticity and memory formation. This is mainly due to various functions of MTs in neurons; MTs are involved in dendritic spine formation, axonal transportation, neuronal polarity, and receptor trafficking. Recent studies from our group and other labs have suggested the possible role of brain MT dynamicity and activity in memory; however, there is a need for more detailed studies regarding this aspect. In this study, we have tried to evaluate the importance of microtubule dynamicity rather than stability in memory formation in vivo. In order to investigate the role of MT stability in memory formation, we treated mice with paclitaxel-a classic microtubule-stabilizing agent. We then studied the behavior of treated animals using Morris water maze (MWM) test. To measure the effect of injected paclitaxel on MT polymerization kinetics, we conducted polymerization assays on brain extracts of the same paclitaxel-treated animals. Our results show that paclitaxel treatment affects animals' memory in a negative way and treated animals behave poorly in MWM compared to control group. In addition, our kinetics studies show that MT stability is significantly increased in brain extracts from paclitaxel-treated mice, but MT dynamics is reduced. Thus, we suggest that dynamicity is a very important feature of MT protein structures, and regarding memory formation, dynamicity is more important than stability and high activity.
Department of Biochemistry, Institute of Biochemistry and Biophysics (IBB), University of Tehran, Qods Street, Tehran, 1417614411, Iran.
Deyhim
D
Atarod
Ghazaleh
G
Eskandari-Sedighi
Farid
F
Pazhoohi
Seyed Morteza
SM
Karimian
Mojtaba
M
Khajeloo
Gholam Hossein
GH
Riazi
D000818:Animals; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008870:Microtubules / Q000187:drug effects* / Q000378:metabolism; D017239:Paclitaxel / Q000494:pharmacology* / Q000633:toxicity; D050257:Tubulin Modulators / Q000494:pharmacology* / Q000633:toxicity
D050257:Tubulin Modulators; D017239:Paclitaxel