| Parkinson’s disease(PD) is one of the typical neurodegenerative diseases. The pathogenesis of PD manifest the damage of dopaminergic neurons in substantia nigra,and the formation of intra-neuronal inclusions called Lewy bodies, which are mainly comprised of alpha-synuclein. The typical features of PD include static tremor,muscle rigidity, bradykinesia and postural reflex. However, non-motor symptoms,such as anxiety, olfactory disorders, cognitive decline, spatial learning and memory damage, appearing before or in parallel with motor deficits in PD. Nevertheless,the underlying mechanisms of non-motor sympotoms remain largely unknown.Alpha-synuclein A53 T transgenic mouse model is a typical animal model to study the effects of alpha-synuclein accumulation on the development of PD. Abnormalα-synuclein were found in this PD model mice. In addition, the motor symptoms emerged later in this model mice. So, the mice may serve as an ideal PD model for the studies of non-motor symptoms. However, evidences on the changes of olfactory function in these mice are absent until now. Moreover, studies on the changes of spatial learning and memory abilities are limited and inconsistent. A large number of studies suggested that inhibition of adult neurogenesis emerged prior to the accumulation of alpha-synuclein and neuronal degeneration. Adult neurogenesis occurs within two areas in the adult brain. One is the subgranular zone(SGZ) of the hippocampus, the other is the subventricular zone(SVZ), a structure known to be critical for olfactory discrimination. However, the relationships between adult neurogenesis and changes in olfactory and learning and memory functions are not observed in the A53 T transgenic mice.By a combination of elevated plus-maze test, olfactory discrimination test, fine odor discrimination test, rota-rod test, water-maze test and fear conditioning test, the anxiety behavior, olfactory ability, the learning and memory ability, as well as the correlation with the motor symptoms were investigated in the A53 T transgenic mice.Then, we used immunofluorescent labeling to observe the adult neurogenesis in hippocampal dentate gyrus region and lateral ventricle ependymal to explore the possible mechanisms of behavior changes. The results are as follows:1. The elevated plus maze tests showed that 6-months-old A53 T transgenic mice stayed longer in the open arms than the control mice(P<0.05), suggested theanti-anxiety behaviors emerged in the 6-months-old A53 T transgenic mice. The12-months-old A53 T transgenic mice traveled a greater distance in the elevated plus maze tests than the control mice(P<0.05), suggested that the 12-months-old A53 T transgenic mice exhibit a hyperactivity behavior.2. The olfactory discrimination tests showed that the control mice spent more time on smelling old bedding than new bedding at 3,6,9,12 months old(P<0.05),3,6,9,12-months-old A53 T transgenic mice spent similar time on smelling the new and old bedding(P>0.05). These results demonstrated that A53 T transgenic mice exhibit olfactory discrimination disorders.3. The fine odor discrimination tests showed that 12-months-old A53 T transgenic mice had significantly lower correct recognition than the control group mice to discriminate the two kinds of different concentrations of mixed odors(P>0.05),indicated that 12-months-old A53 T transgenic mice appear fine odor discrimination disorders.4. The rota-rod tests showed that 12-months-old A53 T transgenic mice spent more time on staying at the rod than the control mice(P<0.05), indicated that12-months-old A53 T transgenic mice had better motor coordination ability than the control mice.5. Morris water maze tests showed that 3-months-old A53 T transgenic mice spent more time to search the platform in the training quadrant than the other quadrants at day 3 in the probe section(P<0.05). However, it took 7 days to remember the training quadrant in the control mice(P<0.05). In the reverse learning tests, it took 3 days for the 3-months-old A53 T transgenic mice to remember the training quadrant, but the control mice spent 5 days to remember the training quadrant. These results indicate that 3-months-old A53 T transgenic mice exhibit an abnormal enhancement of spatial learning and memory abilities. These 9-months-old A53 T transgenic mice spent more time to search the platform in the training quadrant than the other quadrants at day 3in the probe section(P<0.05). However, it took 7 days to remember the training quadrant in the control mice(P<0.05). As for reverse learning, it took 5 days for the3-months-old A53 T transgenic mice to remember the training quadrant, however the control mice spent 6 days to remember the training quadrant. These results indicate that 9-months-old A53 T transgenic mice exhibit an abnormal enhancement of spatial learning and memory abilities.6. The contextual fear conditioning tests showed a prolonged freezing time in context A without electric shock in the transgenic mice compared to that of control(P<0.05), suggested that the space memory ability of 3-months-old A53 T transgenic mice is improved.7. The immunofluorescent labeling studies demonstrated that no obvious changes were observed in the numbers of both Brd U+neurons and Brd U+/DCX+double staining neurons in SVZ and SGZ at 3-months-old A53 T transgenic mice(P>0.05).In summary, in the present studies, we found that 3-months-old A53 T transgenic mice exhibit an improvement of the spatial learning and memory abilities,6-months-old A53 T transgenic mice appear an anti-anxiety behavior and an olfactory discrimination disorders, the 12-months-old A53 T transgenic mice exhibit a hyperactivity behavior. These results show that in the early stage of their lifespan, the A53 T transgenic mice exhibit anti-anxiety, olfactory discrimination disorders and an improved spatial learning and memory abilities, which are prior to the motor symptoms. However, the immunofluorescent results demonstrated that adult neurogenesis are normal in these mice. Further studies are required to testify the possible mechanisms involved. |
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