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      Treadmill Exercise Improves Motor Function and Short-term Memory by Enhancing Synaptic Plasticity and Neurogenesis in Photothrombotic Stroke Mice

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          Abstract

          Purpose

          Thrombotic stroke is a type of ischemic stroke characterized by motor dysfunction and memory impairments. In the present study, the effect of treadmill exercise on motor function and short-term memory was evaluated in relation with synaptic plasticity in the mice with photothrombotic stroke.

          Methods

          Photothrombotic stroke was induced by cortical photothrombotic vascular occlusion. The mice in the treadmill exercise groups performed running on a motorized treadmill for 28 days. Motor function was determined using rota-rod test and foot fault test. Step-through avoidance task was conducted to evaluate short-term memory. Immunohistochemistry for 5-bromo-2′-deoxyuridine and doublecortin was conducted to detect new cell generation. Postsynaptic density protein 95, synaptophysin, brain-derived neurotrophic factor (BDNF), and tyrosine kinase B receptor (TrkB) were determined using western blot. The number of dendritic spines was determined using Golgi stain.

          Results

          Treadmill exercise improved motor function and short-term memory in mice with the photothrombotic stroke. The infarct size was reduced and the number of dendritic spines and expression of postsynaptic density protein 95 and synaptophysin in the peri-infarct cortex and hippocampus were increased by treadmill exercise in photothrombotic stroke mice. Treadmill exercise enhanced neurogenesis through increasing the expression of the hippocampal BDNF and TrkB in photothrombotic stroke mice.

          Conclusions

          Treadmill exercise improved motor function and short-term memory through increasing synaptic plasticity and neurogenesis in photothrombotic stroke mice. Treadmill exercise can be used as an effective treatment strategy to improve brain function related to stroke.

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          Most cited references28

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          Functional assessments in the rodent stroke model

          Stroke is a common cause of permanent disability accompanied by devastating impairments for which there is a pressing need for effective treatment. Motor, sensory and cognitive deficits are common following stroke, yet treatment is limited. Along with histological measures, functional outcome in animal models has provided valuable insight to the biological basis and potential rehabilitation efforts of experimental stroke. Developing and using tests that have the ability to identify behavioral deficits is essential to expanding the development of translational therapies. The present aim of this paper is to review many of the current behavioral tests that assess functional outcome after stoke in rodent models. While there is no perfect test, there are many assessments that are sensitive to detecting the array of impairments, from global to modality specific, after stroke.
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            Radiation-induced impairment of hippocampal neurogenesis is associated with cognitive deficits in young mice.

            Advances in the management of pediatric brain tumors have increased survival rates in children, but their quality of life is impaired due to cognitive deficits that arise from irradiation. The pathogenesis of these deficits remains unknown, but may involve reduced neurogenesis within the hippocampus. To determine the acute radiosensitivity of the dentate subgranular zone (SGZ), 21-day-old C57BL/J6 male mice received whole brain irradiation (2-10 Gy), and 48 h later, tissue was assessed using immunohistochemistry. Proliferating SGZ cells and their progeny, immature neurons, were decreased in a dose-dependent fashion. To determine if acute changes translated into long-term alterations in neurogenesis, mice were given a single dose of 5 Gy, and 1 or 3 months later, proliferating cells were labeled with 5-bromo-2'-deoxyuridine (BrdU). Confocal microscopy was used to determine the percentage of BrdU-labeled cells that showed mature cell phenotypes. X-rays significantly reduced the production of new neurons at both time points, while glial components showed no change or small increases. Measures of activated microglia and infiltrating, peripheral monocytes indicated that reduced neurogenesis was associated with a chronic inflammatory response. Three months after irradiation, changes in neurogenesis were associated with spatial memory retention deficits determined using the Morris water maze. Behavioral training and testing increased the numbers of immature neurons, most prominently in irradiated animals. These data provide evidence that irradiation of young animals induces a long-term impairment of SGZ neurogenesis that is associated with hippocampal-dependent memory deficits.
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              Synapses and memory storage.

              The synapse is the functional unit of the brain. During the last several decades we have acquired a great deal of information on its structure, molecular components, and physiological function. It is clear that synapses are morphologically and molecularly diverse and that this diversity is recruited to different functions. One of the most intriguing findings is that the size of the synaptic response in not invariant, but can be altered by a variety of homo- and heterosynaptic factors such as past patterns of use or modulatory neurotransmitters. Perhaps the most difficult challenge in neuroscience is to design experiments that reveal how these basic building blocks of the brain are put together and how they are regulated to mediate the information flow through neural circuits that is necessary to produce complex behaviors and store memories. In this review we will focus on studies that attempt to uncover the role of synaptic plasticity in the regulation of whole-animal behavior by learning and memory.
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                Author and article information

                Journal
                Int Neurourol J
                Int Neurourol J
                INJ
                International Neurourology Journal
                Korean Continence Society
                2093-4777
                2093-6931
                May 2020
                31 May 2020
                : 24
                : Suppl 1
                : S28-38
                Affiliations
                [1 ]Department of Psychiatry, Myongji Hospital, College of Medicine, Hanyang University, Goyang, Korea
                [2 ]Department of Cardiovascular Neurologic Disease (Stroke Center), College of Korean Medicine, Kyung Hee University, Seoul, Korea
                [3 ]Department of Physiology, College of Medicine, Kyung Hee University, Seoul, Korea
                [4 ]School of Global Sport Studies, Korea University, Sejong, Korea
                [5 ]Metabolomics Laboratory, College of Pharmacy, Korea University, Sejong, Korea
                [6 ]Department of Physical Therapy, College of Health Sciences, Kyungnam University, Changwon, Korea
                Author notes
                Corresponding author: Mal-Soon Shin https://orcid.org/0000-0002-7462-2211 College of Culture and Sports, Division of Global Sport Studies, Korea University, 2511 Sejong-ro, Sejong 30019, Korea E-mail: malsoon@ 123456korea.ac.kr / Tel: +82-044-860-1365 / Fax: +82-044-860-1589
                [*]

                Minha Hong and Mia Kim contributed equally to this study as co-first authors.

                Author information
                http://orcid.org/0000-0003-4924-1107
                http://orcid.org/0000-0002-9164-448X
                http://orcid.org/0000-0001-8832-0874
                http://orcid.org/0000-0001-7033-9630
                http://orcid.org/0000-0002-5821-9203
                http://orcid.org/0000-0003-4348-2217
                http://orcid.org/0000-0002-4877-9784
                http://orcid.org/0000-0002-7462-2211
                Article
                inj-2040158-079
                10.5213/inj.2040158.079
                7285698
                32482055
                e1e091b6-6cd3-4951-bc22-2989b6ece9ff
                Copyright © 2020 Korean Continence Society

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 25 March 2020
                : 28 April 2020
                Categories
                Original Article

                Neurology
                photothrombotic stroke,exercise,short-term memory,synaptic plasticity
                Neurology
                photothrombotic stroke, exercise, short-term memory, synaptic plasticity

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