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.

Social stress is viewed as a factor in the etiology of a variety of psychopathologies such as depression and anxiety. Animal models of social stress are well developed and widely used in studying clinical and physiological effects of stress. Stress is known to significantly affect learning and memory, and this effect strongly depends on the type of stress, its intensity, and duration. It has been demonstrated that chronic and acute stress conditions can change neuronal plasticity, characterized by retraction of apical dendrites, reduction in axonogenesis, and decreased neurogenesis. Various behavioral studies have also confirmed a decrease in learning and memory upon exposure of animals to long-term chronic stress. On the other hand, the close relationship between microtubule (MT) protein network and neuroplasticity controlling system suggests the possibility of MT protein alterations in high stressful conditions. In this work, we have studied the kinetics, activity, and dynamicity changes of MT proteins in the cerebral cortex of male Wistar rats that were subjected to social instability for 35 and 100 days. Our results indicate that MT protein network dynamicity and polymerization ability is decreased under long-term (100 days) social stress conditions.

Abstractα-Synuclein (α-Syn) aggregates are key components of intracellular inclusion bodies characteristic of Parkinson’s disease (PD) and other synucleinopathies. Metal ions have been considered as the important etiological factors in PD since their interactions with α-Syn alter the kinetics of fibrillation. In the present study, we have systematically explored the effects of Zn2+, Cu2+, Ca2+, and Mg2+ cations on α-Syn fibril formation. Specifically, we determined fibrillation kinetics, size, morphology, and secondary structure of the fibrils and their cytotoxic activity. While all cations accelerate fibrillation, we observed distinct effects of the different ions. For example, Zn2+ induced fibrillation by lower tlag and higher kapp and formation of shorter fibrils, while Ca2+ ions lead to formation of longer fibrils, as evidenced by dynamic light scattering and atomic force microscopy studies. Additionally, the morphology of formed fibrils was different. Circular dichroism and attenuated total reflection-Fourier transform infrared spectroscopies revealed higher contents of β-sheets in fibrils. Interestingly, cell viability studies indicated nontoxicity of α-Syn fibrils formed in the presence of Zn2+ ions, while the fibrils formed in the presence of Cu2+, Ca2+, and Mg2+ were cytotoxic. Our results revealed that α-Syn fibrils formed in the presence of different divalent cations have distinct structural and cytotoxic features.

Considering the central role of oxidative stress in the onset and progress of Parkinson’s diseases (PD), search for compounds with antioxidant properties has attracted a growing body of attention. Here, we compare the neuroprotective effect of bulk and nano forms of the polyphenolic fraction of propolis (PFP) against rotenone-induced cellular and animal models of PD. Mass spectrometric analysis of PFP confirmed the presence of multiple polyphenols including kaempferol, naringenin, coumaric acid, vanillic acid, and ferulic acid. In vitro cellular experiments indicate the improved efficiency of the nano form, compared to the bulk form, of PFP in attenuating rotenone-induced cytotoxicity characterized by a decrease in cell viability, release of lactate dehydrogenase, increased ROS generation, depolarization of the mitochondrial membrane, decreased antioxidant enzyme activity, and apoptosis induction. In vivo experiments revealed that while no significant neuroprotection was observed relating to the bulk form, PFP nanosheets were very effective in protecting animals, as evidenced by the improved behavioral and neurochemical parameters, including decreased lipid peroxidation, increased GSH content, and antioxidant enzyme activity enhancement. We suggest that improved neuroprotective effects of PFP nanosheets may be attributed to their increased water solubility and enrichment with oxygen-containing functional groups (such as OH and COOH), leading to increased antioxidant activity of these compounds.

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