Abstract
Spaceflight and simulated microgravity both affect learning and memory, which are mostly controlled by the hippocampus. However, data about molecular alterations in the hippocampus in real or simulated microgravity conditions are limited. Adult Wistar rats were recruited in the experiments. Here we analyzed whether short-term simulated microgravity caused by 3-day hindlimb unloading (HU) will affect the glutamatergic and GABAergic systems of the hippocampus and how dynamic foot stimulation (DFS) to the plantar surface applied during HU can contribute in the regulation of hippocampus functioning. The results demonstrated a decreased expression of vesicular glutamate transporters 1 and 2 (VGLUT1/2) in the hippocampus after 3 days of HU, while glutamate decarboxylase 67 (GAD67) expression was not affected. HU also significantly induced Akt signaling and transcriptional factor CREB that are supposed to activate the neuroprotective mechanisms. On the other hand, DFS led to normalization of VGLUT1/2 expression and activity of Akt and CREB. Analysis of exocytosis proteins revealed the inhibition of SNAP-25, VAMP-2, and syntaxin 1 expression in DFS group proposing attenuation of excitatory neurotransmission. Thus, we revealed that short-term HU causes dysregulation of glutamatergic system of the hippocampus, but, at the same time, stimulates neuroprotective Akt-dependent mechanism. In addition, most importantly, we demonstrated positive effect of DFS on the hippocampus functioning that probably depends on the regulation of neurotransmitter exocytosis.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data Availability
The datasets used and/or analyzed in the current study are available from the corresponding author upon reasonable request.
References
Abidin I, Aydin-Abidin S, Bodur A, Ince I, Alver A (2018) Brain-derived neurotropic factor (BDNF) heterozygous mice are more susceptible to synaptic protein loss in cerebral cortex during high fat diet. Arch Physiol Biochem 124(5):442–447. https://doi.org/10.1080/13813455.2017.1420666
Anand KS, Dhikav V (2012) Hippocampus in health and disease: an overview. Ann Indian Acad Neurol 15(4):239–246. https://doi.org/10.4103/0972-2327.104323
Asada H, Kawamura Y, Maruyama K, Kume H, Ding R, Ji FY, Kanbara N, Kuzume H, Sanbo M, Yagi T, Obata K (1996) Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures. Biochem Biophys Res Commun 229(3):891–895
Asada H, Kawamura Y, Maruyama K, Kume H, Ding RG, Kanbara N, Kuzume H, Sanbo M, Yagi T, Obata K (1997) Cleft palate and decreased brain gamma-aminobutyric acid in mice lacking the 67-kDa isoform of glutamic acid decarboxylase. Proc Natl Acad Sci USA 94(12):6496–6499. https://doi.org/10.1073/pnas.94.12.6496
Bayascas JR, Alessi DR (2005) Regulation of Akt/PKB Ser473 phosphorylation. Mol Cell 18(2):143–145. https://doi.org/10.1016/j.molcel.2005.03.020
Biswal S, Das D, Barhwal K, Kumar A, Nag TC, Thakur MK, Hota SK, Kumar B (2017) Epigenetic regulation of SNAP25 prevents progressive glutamate excitotoxicty in hypoxic CA3 neurons. Mol Neurobiol 54(8):6133–6147. https://doi.org/10.1007/s12035-016-0156-0
Bliznyuk A, Hollmann M, Grossman Y (2019) High pressure stress response: involvement of NMDA receptor subtypes and molecular markers. Front Physiol 10:1234. https://doi.org/10.3389/fphys.2019.01234
Boer U, Alejel T, Beimesche S, Cierny I, Krause D, Knepel W, Flugge G (2007) CRE/CREB-driven up-regulation of gene expression by chronic social stress in CRE-luciferase transgenic mice: reversal by antidepressant treatment. PLoS ONE 2(5):e431. https://doi.org/10.1371/journal.pone.0000431
Borchers AT, Keen CL, Gershwin ME (2002) Microgravity and immune responsiveness: implications for space travel. Nutrition 18(10):889–898
Casler JG, Cook JR (1999) Cognitive performance in space and analogous environments. Int J Cogn Ergonomics 3(4):351–372. https://doi.org/10.1207/s15327566ijce0304_5
Dagda RK, Das Banerjee T (2015) Role of protein kinase A in regulating mitochondrial function and neuronal development: implications to neurodegenerative diseases. Rev Neurosci 26(3):359–370. https://doi.org/10.1515/revneuro-2014-0085
Day JR, Frank AT, O'Callaghan JP, DeHart BW (1998) Effects of microgravity and bone morphogenetic protein II on GFAP in rat brain. J Appl Physiol 85(2):716–722. https://doi.org/10.1152/jappl.1998.85.2.716
Dekeyzer S, De Kock I, Nikoubashman O, Vanden Bossche S, Van Eetvelde R, De Groote J, Acou M, Wiesmann M, Deblaere K, Achten E (2017) "Unforgettable"—a pictorial essay on anatomy and pathology of the hippocampus. Insights Imaging 8(2):199–212. https://doi.org/10.1007/s13244-016-0541-2
Demertzi A, Van Ombergen A, Tomilovskaya E, Jeurissen B, Pechenkova E, Di Perri C, Litvinova L, Amico E, Rumshiskaya A, Rukavishnikov I, Sijbers J, Sinitsyn V, Kozlovskaya IB, Sunaert S, Parizel PM, Van de Heyning PH, Laureys S, Wuyts FL (2016) Cortical reorganization in an astronaut's brain after long-duration spaceflight. Brain Struct Funct 221(5):2873–2876. https://doi.org/10.1007/s00429-015-1054-3
Erlander MG, Tobin AJ (1991) The structural and functional heterogeneity of glutamic acid decarboxylase: a review. Neurochem Res 16(3):215–226
Fdez E, Hilfiker S (2006) Vesicle pools and synapsins: new insights into old enigmas. Brain Cell Biol 35(2–3):107–115. https://doi.org/10.1007/s11068-007-9013-4
Feng L, Liu XM, Cao FR, Wang LS, Chen YX, Pan RL, Liao YH, Wang Q, Chang Q (2016) Anti-stress effects of ginseng total saponins on hindlimb-unloaded rats assessed by a metabolomics study. J Ethnopharmacol 188:39–47. https://doi.org/10.1016/j.jep.2016.04.028
Grigoriev AI, Kaplansky AS, Durnova GN, Popova IA (1997) Biochemical and morphological stress-reactions in humans and animals in microgravity. Acta Astronaut 40(1):51–56
Gronli J, Bramham C, Murison R, Kanhema T, Fiske E, Bjorvatn B, Ursin R, Portas CM (2006) Chronic mild stress inhibits BDNF protein expression and CREB activation in the dentate gyrus but not in the hippocampus proper. Pharmacol Biochem Behav 85(4):842–849. https://doi.org/10.1016/j.pbb.2006.11.021
Hackett JT, Ueda T (2015) Glutamate release. Neurochem Res 40(12):2443–2460. https://doi.org/10.1007/s11064-015-1622-1
Hemmings BA, Restuccia DF (2012) PI3K-PKB/Akt pathway. Cold Spring Harbor Perspect Biol 4(9):a011189. https://doi.org/10.1101/cshperspect.a011189
Hertz L, Chen Y (2017) Integration between glycolysis and glutamate-glutamine cycle flux may explain preferential glycolytic increase during brain activation, Requiring Glutamate. Front Integr Neurosci 11:18. https://doi.org/10.3389/fnint.2017.00018
Hetman M, Gozdz A (2004) Role of extracellular signal regulated kinases 1 and 2 in neuronal survival. Eur J Biochem 271(11):2050–2055. https://doi.org/10.1111/j.1432-1033.2004.04133.x
Jin H, Wu H, Osterhaus G, Wei J, Davis K, Sha D, Floor E, Hsu CC, Kopke RD, Wu JY (2003) Demonstration of functional coupling between gamma -aminobutyric acid (GABA) synthesis and vesicular GABA transport into synaptic vesicles. Proc Natl Acad Sci USA 100(7):4293–4298. https://doi.org/10.1073/pnas.0730698100
Jovanovic JN, Benfenati F, Siow YL, Sihra TS, Sanghera JS, Pelech SL, Greengard P, Czernik AJ (1996) Neurotrophins stimulate phosphorylation of synapsin I by MAP kinase and regulate synapsin I-actin interactions. Proc Natl Acad Sci USA 93(8):3679–3683. https://doi.org/10.1073/pnas.93.8.3679
Jovanovic JN, Czernik AJ, Fienberg AA, Greengard P, Sihra TS (2000) Synapsins as mediators of BDNF-enhanced neurotransmitter release. Nat Neurosci 3(4):323–329. https://doi.org/10.1038/73888
Jovanovic JN, Sihra TS, Nairn AC, Hemmings HC Jr, Greengard P, Czernik AJ (2001) Opposing changes in phosphorylation of specific sites in synapsin I during Ca2+-dependent glutamate release in isolated nerve terminals. J Neurosci 21(20):7944–7953
Kaidanovich-Beilin O, Woodgett JR (2011) GSK-3: functional insights from cell biology and animal models. Front Mol Neurosci 4:40. https://doi.org/10.3389/fnmol.2011.00040
Kokhan VS, Matveeva MI, Bazyan AS, Kudrin VS, Mukhametov A, Shtemberg AS (2017) Combined effects of antiorthostatic suspension and ionizing radiation on the behaviour and neurotransmitters changes in different brain structures of rats. Behav Brain Res 320:473–483. https://doi.org/10.1016/j.bbr.2016.10.032
Koppelmans V, Bloomberg JJ, De Dios YE, Wood SJ, Reuter-Lorenz PA, Kofman IS, Riascos R, Mulavara AP, Seidler RD (2017) Brain plasticity and sensorimotor deterioration as a function of 70 days head down tilt bed rest. PLoS ONE 12(8):e0182236. https://doi.org/10.1371/journal.pone.0182236
Kozlovskaya I, Dmitrieva I, Grigorieva L, Kirenskaya A, Kreidich Y (1988) Gravitational mechanisms in the motor system. Studies in real and simulated weightlessness. In: Gurfinkel VS, Ioffe ME, Massion J, Roll JP (eds) Stance and motion: facts and concepts. Springer, Boston, pp 37–48
Kulikova EA, Kulikov VA, Sinyakova NA, Kulikov AV, Popova NK (2017) The effect of long-term hindlimb unloading on the expression of risk neurogenes encoding elements of serotonin-, dopaminergic systems and apoptosis; comparison with the effect of actual spaceflight on mouse brain. Neurosci Lett 640:88–92. https://doi.org/10.1016/j.neulet.2017.01.023
Kyparos A, Feeback DL, Layne CS, Martinez DA, Clarke MS (2005) Mechanical stimulation of the plantar foot surface attenuates soleus muscle atrophy induced by hindlimb unloading in rats. J Appl Physiol 99(2):739–746. https://doi.org/10.1152/japplphysiol.00771.2004
Layne CS, Mulavara AP, Pruett CJ, McDonald PV, Kozlovskaya IB, Bloomberg JJ (1998) The use of in-flight foot pressure as a countermeasure to neuromuscular degradation. Acta Astronaut 42(1–8):231–246
Lee YI, Kim YG, Pyeon HJ, Ahn JC, Logan S, Orock A, Joo KM, Lorincz A, Deak F (2019) Dysregulation of the SNARE-binding protein Munc18-1 impairs BDNF secretion and synaptic neurotransmission: a novel interventional target to protect the aging brain. Geroscience 41(2):109–123. https://doi.org/10.1007/s11357-019-00067-1
Li K, Guo X, Jin Z, Ouyang X, Zeng Y, Feng J, Wang Y, Yao L, Ma L (2015) Effect of simulated microgravity on human brain gray matter and white matter-evidence from MRI. PLoS ONE 10(8):e0135835. https://doi.org/10.1371/journal.pone.0135835
Lonze BE, Ginty DD (2002) Function and regulation of CREB family transcription factors in the nervous system. Neuron 35(4):605–623
Mann EO, Paulsen O (2007) Role of GABAergic inhibition in hippocampal network oscillations. Trends Neurosci 30(7):343–349. https://doi.org/10.1016/j.tins.2007.05.003
Manners MT, Brynildsen JK, Schechter M, Liu X, Eacret D, Blendy JA (2019) CREB deletion increases resilience to stress and downregulates inflammatory gene expression in the hippocampus. Brain Behav Immun. https://doi.org/10.1016/j.bbi.2019.06.035
Manning BD, Toker A (2017) AKT/PKB signaling: navigating the network. Cell 169(3):381–405. https://doi.org/10.1016/j.cell.2017.04.001
Miller JD, McMillen BA, McConnaughey MM, Williams HL, Fuller CA (1989) Effects of microgravity on brain neurotransmitter receptors. Eur J Pharmacol 161(2–3):165–171
Miller JC, Jimenez P, Mathe AA (2007) Restraint stress influences AP-1 and CREB DNA-binding activity induced by chronic lithium treatment in the rat frontal cortex and hippocampus. Int J Neuropsychopharmacol 10(5):609–619. https://doi.org/10.1017/S1461145706007279
Morey-Holton ER, Globus RK (2002) Hindlimb unloading rodent model: technical aspects. J Appl Physiol 92(4):1367–1377. https://doi.org/10.1152/japplphysiol.00969.2001
Nagamatsu S, Nakamichi Y, Yamamura C, Matsushima S, Watanabe T, Ozawa S, Furukawa H, Ishida H (1999) Decreased expression of t-SNARE, syntaxin 1, and SNAP-25 in pancreatic beta-cells is involved in impaired insulin secretion from diabetic GK rat islets: restoration of decreased t-SNARE proteins improves impaired insulin secretion. Diabetes 48(12):2367–2373. https://doi.org/10.2337/diabetes.48.12.2367
Naumenko VS, Kulikov AV, Kondaurova EM, Tsybko AS, Kulikova EA, Krasnov IB, Shenkman BS, Sychev VN, Bazhenova EY, Sinyakova NA, Popova NK (2015) Effect of actual long-term spaceflight on BDNF, TrkB, p75, BAX and BCL-XL genes expression in mouse brain regions. Neuroscience 284:730–736. https://doi.org/10.1016/j.neuroscience.2014.10.045
Ostenson CG, Gaisano H, Sheu L, Tibell A, Bartfai T (2006) Impaired gene and protein expression of exocytotic soluble N-ethylmaleimide attachment protein receptor complex proteins in pancreatic islets of type 2 diabetic patients. Diabetes 55(2):435–440. https://doi.org/10.2337/diabetes.55.02.06.db04-1575
Pahlevani P, Fatahi Z, Moradi M, Haghparast A (2014) Morphine-induced conditioned place preference and the alterations of p-ERK p-CREB and c-fos levels in hypothalamus and hippocampus the effects of physical stress. Cell Mol Biol (Noisy-le-grand) 60(4):48–55
Popoli M, Yan Z, McEwen BS, Sanacora G (2011) The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci 13(1):22–37. https://doi.org/10.1038/nrn3138
Rai B, Kaur J (2011) Salivary stress markers and psychological stress in simulated microgravity: 21 days in 6 degrees head-down tilt. J Oral Sci 53(1):103–107
Robbins TW, Murphy ER (2006) Behavioural pharmacology: 40+ years of progress, with a focus on glutamate receptors and cognition. Trends Pharmacol Sci 27(3):141–148. https://doi.org/10.1016/j.tips.2006.01.009
Roberts DR, Zhu X, Tabesh A, Duffy EW, Ramsey DA, Brown TR (2015) Structural brain changes following long-term 6 degrees head-down tilt bed rest as an analog for spaceflight. AJNR Am J Neuroradiol 36(11):2048–2054. https://doi.org/10.3174/ajnr.A4406
Roberts DR, Albrecht MH, Collins HR, Asemani D, Chatterjee AR, Spampinato MV, Zhu X, Chimowitz MI, Antonucci MU (2017) Effects of spaceflight on astronaut brain structure as indicated on MRI. N Engl J Med 377(18):1746–1753. https://doi.org/10.1056/NEJMoa1705129
Santos MS, Li H, Voglmaier SM (2009) Synaptic vesicle protein trafficking at the glutamate synapse. Neuroscience 158(1):189–203. https://doi.org/10.1016/j.neuroscience.2008.03.029
Santucci D, Kawano F, Ohira T, Terada M, Nakai N, Francia N, Alleva E, Aloe L, Ochiai T, Cancedda R, Goto K, Ohira Y (2012) Evaluation of gene, protein and neurotrophin expression in the brain of mice exposed to space environment for 91 days. PLoS ONE 7(7):e40112. https://doi.org/10.1371/journal.pone.0040112
Schmitz TW, Correia MM, Ferreira CS, Prescot AP, Anderson MC (2017) Hippocampal GABA enables inhibitory control over unwanted thoughts. Nat Commun 8(1):1311. https://doi.org/10.1038/s41467-017-00956-z
Seino S, Shibasaki T (2005) PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev 85(4):1303–1342. https://doi.org/10.1152/physrev.00001.2005
Shang X, Xu B, Li Q, Zhai B, Xu X, Zhang T (2017) Neural oscillations as a bridge between glutamatergic system and emotional behaviors in simulated microgravity-induced mice. Behav Brain Res 317:286–291. https://doi.org/10.1016/j.bbr.2016.09.063
Smillie KJ, Cousin MA (2012) Akt/PKB controls the activity-dependent bulk endocytosis of synaptic vesicles. Traffic 13(7):1004–1011. https://doi.org/10.1111/j.1600-0854.2012.01365.x
Song SH, Augustine GJ (2015) Synapsin isoforms and synaptic vesicle trafficking. Mol Cells 38(11):936–940. https://doi.org/10.14348/molcells.2015.0233
Song SH, Augustine GJ (2016) Synapsin isoforms regulating GABA release from hippocampal interneurons. J Neurosci 36(25):6742–6757. https://doi.org/10.1523/JNEUROSCI.0011-16.2016
Sudhof TC (2013) A molecular machine for neurotransmitter release: synaptotagmin and beyond. Nat Med 19(10):1227–1231. https://doi.org/10.1038/nm.3338
Tamminga CA, Southcott S, Sacco C, Wagner AD, Ghose S (2012) Glutamate dysfunction in hippocampus: relevance of dentate gyrus and CA3 signaling. Schizophr Bull 38(5):927–935. https://doi.org/10.1093/schbul/sbs062
Taylor CR, Levenson RM (2006) Quantification of immunohistochemistry–issues concerning methods, utility and semiquantitative assessment II. Histopathology 49(4):411–424. https://doi.org/10.1111/j.1365-2559.2006.02513.x
Tyganov SA, Mochalova EP, Belova SP, Sharlo KA, Rozhkov SV, Vilchinskaya NA, Paramonova II, Mirzoev TM, Shenkman BS (2019) Effects of plantar mechanical stimulation on anabolic and catabolic signaling in rat postural muscle under short-term simulated gravitational unloading. Front Physiol 10:1252. https://doi.org/10.3389/fphys.2019.01252
Van Ombergen A, Demertzi A, Tomilovskaya E, Jeurissen B, Sijbers J, Kozlovskaya IB, Parizel PM, Van de Heyning PH, Sunaert S, Laureys S, Wuyts FL (2017a) The effect of spaceflight and microgravity on the human brain. J Neurol 264(Suppl 1):18–22. https://doi.org/10.1007/s00415-017-8427-x
Van Ombergen A, Laureys S, Sunaert S, Tomilovskaya E, Parizel PM, Wuyts FL (2017b) Spaceflight-induced neuroplasticity in humans as measured by MRI: what do we know so far? NPJ Microgravity 3:2. https://doi.org/10.1038/s41526-016-0010-8
Vecchio LM, Meng Y, Xhima K, Lipsman N, Hamani C, Aubert I (2018) The neuroprotective effects of exercise: maintaining a healthy brain throughout aging. Brain Plast 4(1):17–52. https://doi.org/10.3233/BPL-180069
Waltereit R, Weller M (2003) Signaling from cAMP/PKA to MAPK and synaptic plasticity. Mol Neurobiol 27(1):99–106. https://doi.org/10.1385/MN:27:1:99
Wang Y, Iqbal J, Liu Y, Su R, Lu S, Peng G, Zhang Y, Qing H, Deng Y (2015) Effects of simulated microgravity on the expression of presynaptic proteins distorting the GABA/glutamate equilibrium–a proteomics approach. Proteomics 15(22):3883–3891. https://doi.org/10.1002/pmic.201500302
Wang T, Chen H, Lv K, Ji G, Zhang Y, Wang Y, Li Y, Qu L (2017) iTRAQ-based proteomics analysis of hippocampus in spatial memory deficiency rats induced by simulated microgravity. J Proteomics 160:64–73. https://doi.org/10.1016/j.jprot.2017.03.013
Wilson NR, Kang J, Hueske EV, Leung T, Varoqui H, Murnick JG, Erickson JD, Liu G (2005) Presynaptic regulation of quantal size by the vesicular glutamate transporter VGLUT1. J Neurosci 25(26):6221–6234. https://doi.org/10.1523/JNEUROSCI.3003-04.2005
Wise KC, Manna SK, Yamauchi K, Ramesh V, Wilson BL, Thomas RL, Sarkar S, Kulkarni AD, Pellis NR, Ramesh GT (2005) Activation of nuclear transcription factor-kappaB in mouse brain induced by a simulated microgravity environment. In vitro Cell Dev Biol Anim 41(3–4):118–123. https://doi.org/10.1290/0501006.1
Yasuhara T, Hara K, Maki M, Matsukawa N, Fujino H, Date I, Borlongan CV (2007) Lack of exercise, via hindlimb suspension, impedes endogenous neurogenesis. Neuroscience 149(1):182–191. https://doi.org/10.1016/j.neuroscience.2007.07.045
Acknowledgements
We are grateful to Dr. Pavel Musienko for critical discussion of the data and the manuscript. Part of the analysis was done at Research Resource Center #441590 at Sechenov Institute of Evolutionary Physiology and Biochemistry.
Funding
This study was supported by grants from RFBR 20-015-00062 (MVG), 17-29-01029-ofi_m (BSS), and 17-29-01034-ofi_m (NSM) and by Russian Government program.
Author information
Authors and Affiliations
Contributions
ASB performed experiments, analyzed the data, and revising manuscript. SAT and NSM performed animal experiments. SDN and AAN performed immunohistochemical staining and data analysis. BSS designed the experiments and revised manuscript. MVG conceived the study, designed the experiments, and wrote the manuscript. All authors discussed and commented on the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
Below is the link to the electronic supplementary material.
10571_2020_922_MOESM1_ESM.pdf
Online Resource 1. Neither hindlimb unloading nor dynamic foot stimulation altered GABA expression in the hippocampus. a-c – GAD67 immunostaining of the hippocampus of control rats (a), the rats of DFS group (b) and after 3-day HU (c). DGg – granular layer of the dentate gyrus; DGm – molecular layer of the dentate gyrus; h – the hilus. d, e – western blot analysis of GAD67 expression: d – representative images of western blots of GAD67 and GAPDH; e – analysis of GAD67 expression in the hippocampus by calculation of the ration between GAD67 and GAPDH. n=8 (number of animals) for each group. f – qRT-PCR analysis demonstrated that GAD65 mRNA and GAD67 mRNA levels in the hippocampus of DFS and HU rats were not changed. n=6 for each group. c – control, DFS – the rats with dynamic foot stimulation during 3-day hindlimb unloading; HU – 3-day hindlimb unloading. Data are shown as median with interquartile range. (PDF 4065 kb)
10571_2020_922_MOESM2_ESM.pdf
Online Resource 2. Ponceau S staining of western blot membranes. After protein transfer, the nitrocellulose membranes were stained with Ponceau S and optical density of the selected zones for SNAP-25 and VAMP-2 (a), and for syntaxin 1 (b) analysis were calculated for analysis of SNAP-25, VAMP-2 and for syntaxin 1 expression. (PDF 3301 kb)
10571_2020_922_MOESM3_ESM.pdf
Online Resource 3. PKA activity do not change after hindlimb unloading or dynamic foot stimulation. a, b – western blot analysis of pPKA substrate phosphorylation (a) with Ponceau S staining as a standard (b). c – the result of PKA substrate phosphorylation. c – control, DFS – the rats with dynamic foot stimulation during 3-day hindlimb unloading; HU – 3-day hindlimb unloading. Data are shown as median with interquartile range. (PDF 2522 kb)
Rights and permissions
About this article
Cite this article
Berezovskaya, A.S., Tyganov, S.A., Nikolaeva, S.D. et al. Dynamic Foot Stimulations During Short-Term Hindlimb Unloading Prevent Dysregulation of the Neurotransmission in the Hippocampus of Rats. Cell Mol Neurobiol 41, 1549–1561 (2021). https://doi.org/10.1007/s10571-020-00922-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10571-020-00922-2