Secondary Metabolites and Amino Acids in the Neocortex of the Long-Tailed Ground Squirrel Urocitellus undulatus at Different Stages of Hibernation

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

This study is a continuation of our previous research aimed at investigating changes in the pools of amino acids in the myocardium of the ground squirrel during winter torpor. Neurochemical profiles of amino acids and the secondary metabolites (taurine, phosphoserine, and cysteic acid) were explored in the neocortex of the ground squirrel at different stages of torpor: in the beginning of torpor (2–3 days) and during prolonged torpor (9–10 days), as well as during short-term winter arousal (winter activity, euthermia). Reduced excitatory neurotransmitter levels (glutamate by 7% and 14%; aspartate by 25% and 52% in a coordinated manner and the increased level of GABA, the main transmission inhibitor (by 50% and 67%) were observed from the onset of the torpor entry and at the end of the torpor arousal, respectively. Alanine, which was formed in negligible amounts in the neocortex in the summer season, increased at the initial stage of hibernation and after multiday torpor bout (by 98% and 126%, respectively), indicating a partial switch to anaerobic glycolysis. Short-term inter-bout euthermia returned levels of these substances back to normal. The behavior of glutamate and aspartate, the anaplerotic substrates, that supported cycling of the tricarboxylic acid cycle during torpor and winter activity periods was like their responses in the myocardium, though differed quantitatively. The responses of the neuromodulators such as glycine, threonine, and lysine differed radically when compared to their responses in the myocardium. No changes in taurine and phosphoserine pools were detected, but the level of cysteic acid decreased compared to the summer control from 0.51 ± 0.06 μmol/g to 0.07 ± 0.01 μmol/g at the end of torpor, while during winter euthermia it became 2 times lower than the summer level. Our data suggest that metabolic pathways, involving anaplerotic amino acids of the neocortex, are more active than the myocardium during winter torpor, while the pools of neuromodulators that regulate inhibition processes, increase.

About the authors

M. V Karanova

Institute of Cell Biophysics, Russian Academy of Sciences

Email: karanovari@mail.ru
Institutskaya ul. 3, Pushchino, Moscow Region, 142290, Russia

N. M Zakharovа

Institute of Cell Biophysics, Russian Academy of Sciences

Institutskaya ul. 3, Pushchino, Moscow Region, 142290, Russia

References

  1. Demin N. N., Shortanova T. H., and Emirbekov E. Z. Neurochemistry of hibernation in mammals (Science, Leningrad, 1988).
  2. Drew K. L., Buck C. L., Barnes B. M., Christian S. L., Rasley B. T., and Harris M. B. Central nervous system regulation of hibernation: implications for metabolic suppression and ischemia tolerance. Neurochemistry, 102, 1713–1726 (2007). doi: 10.1111/j.14714159.2007.04675.x
  3. Белоусов А. В. Роль центральной нервной системы в контроле зимней спячки. Успехи физиол. наук, 2, 109–123 (1993).
  4. Giroud S., Habold C., Nespolo R. F., Mejías C., Terrien J., Logan S. M., Henning R. H., and Storey K. B. The Torpid State: Recent Advances in Metabolic Adaptations and Protective Mechanisms. Front. Physiol., 11, 623665 (2021). doi: 10.3389/fphys.2020.623665
  5. Fan T. T., Ni J. J., Dong W. C., An L. Z., Xiang Y., and Cao S. Q. Effect of low temperature on profilins and ADFs transcription and actin cytoskeleton reorganization in Arabidopsis et al., Biol. Plant., 59, 793–796 (2015). doi: 10.1007/s10535-015-0546-6
  6. Mednikova Yu. S., Zakharova N. M., Pasikova N. V., and D. N. Voronkov. Comparative Analysis of Morphofunctional Features of Cortical Neurons in Ground Squirrels and Guinea Pigs under Hypothermia. J. Evol. Biochem. Physiol., 53 (4), 331–339 (2017). doi: 10.1134/S002209301704010X
  7. Largo C., Cuevas P. P., Somjen G. G., Martín del Río R., and Herreras O. The effect of depressing glial function in rat brain in situ on ion homeostasis, synaptic transmission, and neuron survival. J. Neurosci., 16 (3), 1219–1229 (1996). doi: 10.1523/JNEUROSCI.16-03-01219.1996
  8. Zakharova N. M., Voronkov D. N., Khudoerkov R. M., Pasikova N. V., and Mednikova Yu. S. Glia–Neuron Interactions in the Sensory-Motor Cortex of WarmBlooded Animals (Guinea Pigs and Ground Squirrels) with Different Habitat Conditions and the M-Cholinergic Reaction of the Brain. Biophysics, 63 (2), 207–214 (2018). DOI: 10.1134/ S0006350918020264
  9. Schwartz C., Hampton M., and Andrews M. T. Seasonal and Regional Differences in Gene Expression in the Brain of a Hibernating Mammal. PLoS One, 8 (3), e58427 (2013) doi: 10.1371/journal.pone.0058427
  10. Chen J., Yuan L., Sun M., Zhan L., and Zhan S.. Screening of hibernation-related genes in the brain of Rhinolophus ferrumequinum during hibernation. Comp. Biochem. Physiol. B, Biochem. Mol. Biol., 149 (2), 388–393 (2008). doi: 10.1016/j.cbpb.2007.10.011
  11. Wu G. Amino acids: metabolism, functions, and nutrition. Amino Acids, 37 (1), 1–17 (2009). doi: 10.1007/s00726-009-0269-0
  12. Karanova M. V. and Zakharova N. M. Adaptive Modification of Amino Acid Pools in the Myocardium of a Long-Tailed Ground Squirrel Urocitellus undulatus at Different Stages of Hibernation. J. Evol. Biochem. Physiol., 59 (4), 1027–1036 (2023). doi: 10.1134/S0022093023040038
  13. Karanova M. V. and Zakharova N. M. Pools of Amino Acids of Skeletal Muscle in Yakutian Ground Squirrel Urocitellus undulatus during Different Hibernation Stages. Biophysics, 67 (2), 288–293 (2022). doi: 10.1134/S0006350922020105
  14. Al-Badry K. S. and Taha H. M. Hibernation hypothermia and metabolism in hedgehogs--changes in free amino acids and related compounds. Comp. Biochem. Physiol., 72 (3), 541–547 (1982). doi: 10.1016/0300-9629(82)90120-7
  15. Raheem K. A. and el Mosallamy N. Metabolism of hibernating reptiles. Changes of free amino acids in blood, liver and brain. Comp. Biochem. Physiol. B, Biochem. Mol. Biol., 64 (3), 305–308 (1979). doi: 10.1016/0305-0491(79)90149-4
  16. Forreider B., Pozivilko D., Kawaji Q., GUNK X, and Ding Y. Hibernation-like neuroprotection in stroke by attenuating brain metabolic dysfunction. Prog Neurobiol. 157, 174–187 (2017). doi: 10.1016/j.pneurobio.2016.03.002
  17. Emirbekov E. Z. and Meilanov I. S. Neurochemical changes during hibernation (Pushchino, 1992).
  18. Henry P. G., UNKseth K. R., Tkac I., Drewes L. R., Andrews M. T., and Gruetter R. Brain energy metabolism and neurotransmission at near-freezing temperatures: in vivo (1)H MRS study of a hibernating mammal. J. Neurochem., 101, 1505–1515 (2007). doi: 10.1111/j.1471-4159.2007.04514.x
  19. Osborne P. G. and Hashimoto M. Mammalian cerebral metabolism and amino acids neurotransmission during hibernation. J. Neurochem., 106,1888–1899 (2008). doi: 10.1111/j.1471-4159.2008.05543.x
  20. Spackman D., Stein W., and Moore S. Automatic Recording Apparatus for Use in Chromatography of Amino Acids. Anal. Chem., 30, 1190-1206 (1958).
  21. Ezza H. S. A. and Khadrawy Y. A., Glutamate Excitotoxicity and Neurodegeneration. J. Mol. Genet. Med., 8, 141 (2014). doi: 10.4172/1747-0862.1000141
  22. Andersen J. V., Markussen K. H., Jakobsen E., Schousboe A., Waagepetersen H. S., Rosenberg P. A., and Aldana B. I. Glutamate Metabolism and Recycling at the Excitatory Synapse in Health and Neurodegeneration. Neuropharm., 196, 108719 (2021). doi: 10.1016/j.neuropharm.2021.108719
  23. Watford M. Glutamine and Glutamate: Nonessential or Essential Amino Acids? Anim. Nutr., 1, 119–122 (2015). doi: 10.1016/j.aninu.2015.08.008
  24. Grynberg A. and Demaison L. Fatty Acid Oxidation in the Heart. J. Cardiovasc. Pharmacol. 28 (1), 11–17 (1996). doi: 10.1097/00005344-199600003-00003
  25. Zhang S., Lachance B. B., Mattson M. P., and Jia X.. Glucose metabolic crosstalk and regulation in brain function and diseases. Progr. Neurobiol., 204, 102089 (2021). doi: 10.1016/j.pneurobio.2021.10208
  26. Salceda R. Glycine neurotransmission: Its role in development. Front. Neurosci., 16, 947563 (2022). doi: 10.3389/fnins.2022.947563
  27. Karanova M. V. Impact of Seasonal Temperature Decrease and Cold Shock on the Composition of Free Amino Acids and Phosphomonoethers in Various Organs of Amur Sleeper Perccottus glenii (Eleotridae). J. Ichthyol., 58 (4), 570–579 (2018). doi: 10.1134/S0032945218040069
  28. Karanova M. V. Secondary Metabolites and Aspartic Acid in the Brain of the Frog Rana temporaria as LowTemperature Adaptogens. J. Evol. Biochem. Phys., 56, 218–223 (2020). doi: 10.1134/S0022093020030047
  29. R. Marion, V. Horn, M. Sild, and Ruthazer E. S. Dserine as a gliotransmitter and its roles in brain development and disease. Front. Cell. Neurosci., 7 , 39 (2013). doi: 10.3389/fncel.2013.00039
  30. Lionetti V., Stanley W. C., and Recchia F. A. Modulating fatty acid oxidation in heart failure. Cardiovasc. Res., 90 (2), 202–209 (2011). doi: 10.1093/cvr/cvr038
  31. Benarroch E. E. Brain glucose transporters: Implications for neurologic disease. Neurol., 82 (15), 1374–1379 (2014). doi: 10.1212/WNL.0000000000000328
  32. Andrews M. T., UNKseth K. R., Drewes L. R., and Henry P. G. Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor. Am. J. Physiol. Regul. Integr. Comp. Physiol., 296 (2), R383–R 393 (2009). doi: 10.1152/ajpregu.90795.2008
  33. Watanabe M., Maemura K., Kanbara K., Tamayama T., and Hayasaki H. GABA and GABA Receptors in the Central Nervous System and Other Organs. Int. Rev. Cytol., 213, 1–47 (2002). doi: 10.1016/S0074-7696 (02)13011-7
  34. Andersen J. V. and Schousboe A. Milestone Review: Metabolic dynamics of glutamate and GABA mediated neurotransmission The essential roles of astrocytes. J. Neurochem., 166 (2), 109–137 (2023). doi: 10.1111/jnc.15811
  35. Petroff O. A. C. GABA and Glutamate in the Human Brain. Neuroscientist, 8 (6), 562–573 (2002). doi: 10.1177/107385840223851
  36. Popov V. A., Semenov D. V., Amakhin N. P., Veselkin N. P. Interaction of glutamate and GABA receptors in the receptors of the central nervous system. UNK. J. Physiol., 102 (5), 529–539 (2016).
  37. Nilsson G. E. and Lutz P. L. Role of GABA in hypoxia tolerance, metabolic depression and hibernation—possible links to neurotransmitter evolution. Comp. Biochem. Physiol. Part C. Comp. Pharmacol., 105 (3), 329–336 (1993). doi: 10.1016/0742-8413 (93)90069
  38. Pellerin L. and Magistretti P. J., Glutamate uptake into astrocytes stimulates aerobic glycolysis: a mechanism coupling neuronal activity to glucose utilization. Proc. Natl. Acad. Sci. USA, 91 (22), 10625–10629 (1994). doi: 10.1073/pnas.91.22.10625
  39. Turinsky J., Mukherji B. and Slоviter H. A.. Effects of induced hypothermia on amino acids and glycogen inrat brain. J. Neurochem., 18, 233–235 (1971). doi: 10.1111/j.1471-4159.1971.tb00561.x
  40. Drew K., Harris M., LaManna J., Smith M., Zhu X., and Ma Y. Hypoxia tolerance in mammalian heterotherms J. Exp. Biol., 207, 3155–3162 (2004). doi: 10.1242/jeb.01114
  41. Dave K. R., Christian S. L., Perez-Pinzon M. A., and Drew K. L. Neuroprotection: lessons from hibernators Comp. Biochem. Physiol. B. Biochem. Mol. Biol., 162 (1–3), 1–9 (2012). doi: 10.1016/j.cbpb.2012.01.008
  42. Frerichs K. U. and Hallenbeck J. M.. Hibernation in ground squirrels induces state and species-specific tolerance to hypoxia and aglycemia: an in vitro study in hippocampal slices. J. Cereb. Blood Flow Metab., 18, 168-175 (1998). doi: 10.1097/00004647-199802000-00007
  43. Bekshokov K. S., Emirbekov E. Z. and Emirbekova A. A. Severo-Kavkazskij region. Estestvennye nauki. Prilozhenie, S6, 42(2004).
  44. Langosch D., Becker C. M., and Betz H. The inhibitory glycine receptor: A ligand-gated chloride channel of the central nervous system. Eur. J. Biochem., 194, 1–8 (1990). doi: 10.1111/j.1432-1033.1990.tb19419.x
  45. Lynch J. W. Molecular Structure and Function of the Glycine Receptor Chloride Channel. Physiol. Rev., 84, 1051–1095 (2004). doi: 10.1152/physrev.00042.2003
  46. Bonhaus D. W., Burge B. C., and McNamara J. O. Biochemical evidence that glycine allosterically regulates an NMDA receptor-coupled ion channel. Eur. J. Pharmacol., 142 (3), 489–490 (1987). doi: 10.1016/0014-2999(87)90096-3
  47. Kurbat M. N. and Lelevich V. V. Metabolism of Amino Acids in the Brain. Neurochem. J., 3 (1), 23–28 (2009).
  48. Reis D. J., Golanov E. V., Galea E., and Feinstein D. L. Central neurogenic neuroprotection: central neural systems that protect the brain from hypoxia and ischemia. Ann. NY. Acad. Sci., 835, 168–186 (1997). doi: 10.1111/j.1749-6632.1997.tb48628.x
  49. Ma Y. L., Zhu X., Rivera P. M., Tøien Ø., Barnes B. M., LaManna J. C., Smith M. A., and Drew K. L. Absence of cellular stress in brain after hypoxia induced by arousal from hibernation in Arctic ground squirrels. Am. J. Physiol. Regul. Integr. Comp. Physiol., 289, R1297–R1306 (2005). doi: 10.1152/ajpregu.00260.2005
  50. Hirabayashi Y. and Furuya S. Roles of l-serine and sphingolipid synthesis in brain development and neuronal survival. Progr. Lipid Res., 47 (3), 188–203 (2008). doi: 10.1016/j.plipres.2008.01.003
  51. Murtas G., G. Marcone L., Sacchi S., and Pollegioni L. L-serine synthesis via the phosphorylated pathway in humans. Cell Mol. Life. Sci., 77 (24), 5131–5148 (2020). doi: 10.1007/s00018-020-03574-z
  52. T Maher. J. and Wurtman R. J. L-Threonine administration increases glycine concentrations in the rat central nervous system. Life Sci., 26, 1283–1286 (1980). doi: 10.1016/0024-3205(80)90086-7
  53. Dalangin R., Kim A. and Campbell R. E. The role of amino acids in neurotransmission and f luorescent tools for their detection. Int. J. Mol. Sci., 21 (17), 6197 (2020). doi: 10.3390/ijms21176197
  54. Severyanova L. A., Lazarenko V. A., Plotnikov D. V., Dolgintsev M. E., and Kriukov A. A. L-Lysine as the Molecule Influencing Selective Brain Activity in PainInduced Behavior of Rats. Int. J. Mol. Sci., 20 (8), 1899 (2019). doi: 10.3390/ijms20081899
  55. Karanova M. V. Influence of low temperature on the evolution of amino acid pools adaptive modifications in poikilothermal animals. Int. J. Biochem. Biophys., 1 (2), 33–40 (2013). doi: 10.13189/ijbb.2013.010202
  56. Klunk W. E., McClure R. J., and Pettegrew J. W. Possible roles of L-phosphoserine in the pathogenesis of Alzheimer's disease. Mol. Chem. Neuropathol., 15 (1), 51–73 (1991). doi: 10.1007/BF03161056
  57. Oja S. S. and Saransaari P. Significance of Taurine in the Brain. Adv. Exp. Med. Biol., 975 (1), 89–94 (2017). doi: 10.1007/978-94-024-1079-2_8
  58. El Idrissi A. and Trenkner E. Taurine as a Modulator of Excitatory and Inhibitory Neurotransmission. Neurochem. Res., 29, 189–197 (2004). doi: 10.1023/b:nere.0000010448.17740.6e
  59. Hilgier W., Oja S. S., Saransaari P., and Albrecht J. Taurine prevents ammonia-induced accumulation of cyclic GMP in rat striatum by interaction with GABAA and glycine receptors. Brain Res., 1043 (1–2), 242–246 (2005). doi: 10.1016/j.brainres.2005.02.066
  60. Iwata H., Yamagami S., and Baba A. Cysteine Sulfinic Acid in the Central Nervous System: Specific Binding of [35S] Cysteic Acid to Cortical Synaptic MembranesAn Investigation of Possible Binding Sites for Cysteine Sulfinic Acid. J. Neurochem., 38 (5), 1275–1279 (1982). doi: 10.1111/j.1471-4159.1982.tb07901.x

Copyright (c) 2024 Russian Academy of Sciences

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies