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Acute stress is not acute: sustained enhancement of glutamate release after acute stress involves readily releasable pool size and synapsin I activation

Molecular Psychiatry volume 22, pages 1226–1227 (2017)Cite this article

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Stress-related disorders, such as mood and anxiety disorders, represent one of the great therapeutic challenges for the twenty-first century. Stressful life events impact on the brain and bodily function and represent a major risk factor for the development of neuropsychiatric disorders. The response to stressful events can promote adaptive plasticity and improved cognition, when the physiological stress response is efficiently activated and inactivated in due time, or can exert maladaptive and harmful effects that may trigger psychopathology, when the response is overused or dysregulated.1, 2, 3

It has been shown previously that acute stress and corticosterone (CORT) exert a destabilizing effect on the glutamate system, rapidly enhancing excitatory synaptic transmission in select brain areas.4, 5 Recently, we showed that a 40-min protocol of acute inescapable footshock (FS)-stress rapidly enhances depolarization-evoked glutamate release/transmission in prefrontal and frontal cortex (PFC/FC), by increasing circulating CORT levels.6 Binding to synaptic receptors, CORT induces rapid (non-genomic) enhancement of trafficking of glutamate presynaptic vesicles in perforated synapses, dependent on selective phosphorylation of synapsin I at Ser9. This results into increased size of the readily releasable pool (RRP) of vesicles, which subserves the enhancement of glutamate release from synaptic terminals, prevented by chronic antidepressant treatment.6 In related studies, it was shown that acute FS-stress also dramatically (42.6%) increases the total number of non-perforated synapses in PFC, an effect again partly prevented by antidepressants.7 These findings provided the first evidence that stress-dependent ex novo synaptogenesis of asymmetric synapses is detectable as early as 40 min after start of stress application. In addition, significant atrophy and remodeling of apical dendrites was observed in PFC as early as 24 h after FS-stress, sustained for up to 14 days.8 Therefore, acute stress may induce rapid structural/functional changes in glutamate synapses and also result in sustained remodeling of neural architecture.

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References

  1. McEwen BS . Metabolism 2005; 54: 20–23.

    Article  CAS  Google Scholar 

  2. Joëls M, Baram TZ . Nat Rev Neurosci 2009; 10: 459–466.

    Article  PubMed Central  Google Scholar 

  3. Popoli M, Yan Z, McEwen BS, Sanacora G . Nat Rev Neurosci 2012; 13: 22–37.

    Article  CAS  Google Scholar 

  4. Yuen EY, Liu W, Karatsoreos IN, Ren Y, Feng J, McEwen BS et al. Mol Psychiatry 2011; 16: 156–170.

    Article  CAS  Google Scholar 

  5. Karst H, Berger S, Turiault M, Tronche F, Schütz G, Joëls M . Proc Natl Acad Sci USA 2005; 102: 19204–19207.

    Article  CAS  Google Scholar 

  6. Treccani G, Musazzi L, Perego C, Milanese M, Nava N, Bonifacino T et al. Mol Psychiatry 2014; 19: 433–443.

    Article  CAS  Google Scholar 

  7. Nava N, Treccani G, Liebenberg N, Chen F, Popoli M, Wegener G et al. Int J Neuropsychopharmacol 2015; 18: pii: pyu085.

  8. Nava N, Treccani G, Alabsi A, Kaastrup Mueller H, Elfving B et al. Cereb Cortex 2015; pii: bhv254; e-pub ahead of print.

  9. Izquierdo A, Wellman CL, Holmes A . J Neurosci 2006; 26: 5733–5738.

    Article  CAS  Google Scholar 

  10. Hajszan T, Dow A, Warner-Schmidt JL, Szigeti-Buck K, Sallam NL, Parducz A et al. Biol Psychiatry 2009; 65: 392–400.

    Article  Google Scholar 

  11. Chen Y, Rex CS, Rice CJ, Dubé CM, Gall CM, Lynch G et al. Proc Natl Acad Sci USA 2010; 107: 13123–13128.

    Article  CAS  Google Scholar 

  12. Gorman JM, Docherty JP . J Neuropsychiatry Clin Neurosci 2010; 22: 256–264.

    Article  Google Scholar 

  13. Sanacora G, Treccani G, Popoli M . Neuropharmacology 2012; 62: 63–77.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacological and Biomolecular Sciences, Laboratory of Neuropsychopharmacology and Functional Neurogenomics, University of Milan, Milan, Italy

    L Musazzi, P Tornese, N Sala & M Popoli

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  1. L Musazzi
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  2. P Tornese
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  3. N Sala
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  4. M Popoli
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Correspondence to M Popoli.

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Musazzi, L., Tornese, P., Sala, N. et al. Acute stress is not acute: sustained enhancement of glutamate release after acute stress involves readily releasable pool size and synapsin I activation. Mol Psychiatry 22, 1226–1227 (2017). https://doi.org/10.1038/mp.2016.175

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