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Exercise Prevents Memory Consolidation Defects Via Enhancing Prolactin Responsiveness of CA1 Neurons in Mice Under Chronic Stress

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Abstract

We investigated the effects of regular exercise on chronic stress-induced memory consolidation impairment and its underlying mechanism. We focused on prolactin (PRL)-modulated calcium-permeable (CP)-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors (AMPARs) in neurons in the CA1 stratum lacunosum-moleculare (SLM) area of the dorsal hippocampus. Regular exercise protected against memory retention defects and prevented dendritic retraction in apical distal segments of hippocampal CA1 neurons, as indicated by enhanced dendritic ramification, dendritic length, spine density, and synaptic protein levels following chronic stress. Regular exercise normalized synaptic CP-AMPAR assembly in the hippocampal CA1 SLM area, as evidenced by an enhanced ratio of GluR1 to GluR2 during chronic stress. This alteration in AMPARs was critical to memory retention, whereby memory retention was blunted by local blockage of CP-AMPARs in the SLM of naïve and exercised mice. Regular exercise improved PRL responsiveness in the hippocampal CA1 region during chronic stress, which led to increased binding of PRL to its receptor (PRLR) and PRL-dependent enhancement in phosphorylated signal transducer and activator of transcription 5 levels. The improvement in PRL responsiveness contributed to memory retention during chronic stress, as the protective action of exercise on memory persistence during stress was abolished by PRLR knockdown in the hippocampal CA1 area. Finally, in primary hippocampal cultures, repeated treatment with corticosterone led to decreased AMPAR-mediated Ca2+ influx, which was restored by PRL treatment. The above findings suggest a protective role for exercise against chronic stress-evoked defects in memory consolidation via PRL-modulated incorporation of CP-AMPARs into hippocampal CA1 synapses.

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Funding

This research was supported by a National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (2010-0027945 and 2018R1A2B6003074).

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  1. Yea-Hyun Leem and Jin-Sun Park contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Medicine and Tissue Injury Defense Research Center, School of Medicine, Ewha Womans University, Mok-6-dong 911-1, Yangchun-Ku, Seoul, 158-710, South Korea

    Yea-Hyun Leem, Jin-Sun Park & Hee-Sun Kim

  2. Department of Human Movement, Seoul Women’s University, Seoul, South Korea

    Hyukki Chang

  3. Department of Physical Education, Korea University, Seoul, South Korea

    Jonghoon Park

  4. Department of Brain & Cognitive Sciences, Ewha Womans University, Seoul, South Korea

    Hee-Sun Kim

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  1. Yea-Hyun Leem
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Leem, YH., Park, JS., Chang, H. et al. Exercise Prevents Memory Consolidation Defects Via Enhancing Prolactin Responsiveness of CA1 Neurons in Mice Under Chronic Stress. Mol Neurobiol 56, 6609–6625 (2019). https://doi.org/10.1007/s12035-019-1560-z

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