Transcriptional activity of genes regulating neurogliogenesis and apoptosis in rats trained in morris water maze: the influence of stress and spatial memory formation

Capa

Citar

Texto integral

Resumo

The formation of new neural networks and the modification of pre-existing synaptic contacts, which underlie learning and memory, largely depend on the activity of genes involved in the regulation of the associated processes of neurogliogenesis and apoptosis. At the same time, the identification of changes in the functioning of the genome specific to cognitive functions requires a simultaneous assessment of the influence of stressful factors as a persistent component of all models of laboratory animal learning. The aim of this study was to compare the expression of genes regulating neurogliogenesis (S100А6, Ascl1), and apoptosis (Apaf1, Bax, Casp3, Bcl2) in animals trained in spatial Morris maze and those subjected to forced swimming in accordance with the training regime. The experiments were conducted on young adult male Wistar rats, distributed into the following groups: Training (trained to find a hidden platform in a water maze for 4 days), Control (swimming in a maze without a platform for 4 days) and Intact (staying in home cages). In tissue samples of the hippocampus, prefrontal cortex, and cerebellum obtained immediately after the end of experiments in the maze, the expression of target genes was determined by real-time polymerase chain reaction. It was found that cognitive activity reduces the expression of pro-apoptotic genes, which increases under stress conditions, and, on the contrary, stimulates the activity of genes regulating neurogliogenesis and synaptogenesis in structures relevant for various stages of memory trace formation. The results obtained, are of interest for understanding molecular mechanisms of stress and cognition as well as for determining the targets of therapy for cognitive disorders.

Sobre autores

A. Ratmirov

Federal Research Center for Innovator and Perspective Biomedical and Pharmaceutical Technologies

Moscow, Russia

M. Gruden

Federal Research Center for Innovator and Perspective Biomedical and Pharmaceutical Technologies

Moscow, Russia

Z. Storozheva

Federal Research Center for Innovator and Perspective Biomedical and Pharmaceutical Technologies

Email: storozheva_zi@academpharm.ru
Moscow, Russia

Bibliografia

  1. Chang WL, Hen R (2024) Adult Neurogenesis, Context Encoding, and Pattern Separation: A Pathway for Treating Overgeneralization. Adv Neurobiol 38: 163–193. https://doi.org/ 10.1007/978-3-031-62983-9_10
  2. Forrest MP, Parnell E, Penzes P (2018) Dendritic structural plasticity and neuropsychiatric disease. Nat Rev Neurosci 19(4): 215–234. https://doi.org/10.1038/nrn.2018.16
  3. Pumo GM, Kitazawa T, Rijli FM (2022) Epigenetic and Transcriptional Regulation of Spontaneous and Sensory Activity Dependent Programs During Neuronal Circuit Development. Front Neur Circ 16: 911023. https://doi.org/10.3389/fncir.2022.911023
  4. Petanjek Z, Banovac I, Sedmak D, Hladnik A (2023) Dendritic Spines: Synaptogenesis and Synaptic Pruning for the Developmental Organization of Brain Circuits. Advanc Neurobiol 34: 143–221. https://doi.org/10.1007/978-3-031-36159-3_4
  5. Gomazkov OA (2016) Neurogenesis as an organizing function of the adult brain: is there enough evidence? Biol Bull Rev 6(6): 457–472. https://doi.org/ 10.1134/S2079086416060013
  6. Šimončičová E, Henderson Pekarik K, Vecchiarelli HA, Lauro C, Maggi L, Tremblay MÈ (2024) Adult Neurogenesis, Learning and Memory. Advanc Neurobiol 37: 221–242. https://doi.org/10.1007/978-3-031-55529-9_13
  7. Jurkowski MP, Bettio LK, Woo E, Patten A, Yau SY, Gil-Mohapel J (2020) Beyond the Hippocampus and the SVZ: Adult Neurogenesis Throughout the Brain. Front Cell Neurosci 14: 576444. https://doi.org/10.3389/fncel.2020.576444
  8. Chang WL, Hen R (2024) Adult Neurogenesis, Context Encoding, and Pattern Separation: A athway for Treating Overgeneralization. Advanc Neurobiol 38: 163–193. https://doi.org/10.1007/978-3-031-62983-9_10
  9. Gomazkov OA (2019) Astrocytes as the elements of the regulation of higher brain functions. Neurochem J 13(4): 313–319. https://doi.org/10.1134/s1819712419030073
  10. Machado-Santos AR, Loureiro-Campos E, Patrício P, Araújo B, Alves ND, Mateus-Pinheiro A, Correia JS, Morais M, Bessa JM, Sousa N, Rodrigues AJ, Oliveira JF, Pinto L (2022) Beyond New Neurons in the Adult Hippocampus: Imipramine Acts as a Pro-Astrogliogenic Factor and Rescues Cognitive Impairments Induced by Stress Exposure. Cells 11(3): 390. https://doi.org/10.3390/cells11030390
  11. Toda T, Parylak SL, Linker SB, Gage FH (2019) The role of adult hippocampal neurogenesis in brain health and disease. Mol Psychiatry24(1): 67–87. https://doi.org/10.1038/s41380-018-0036-2
  12. Lambertus M, Geiseler S, Morland C (2024) High-intensity interval exercise is more efficient than medium intensity exercise at inducing neurogenesis. J Physiol 602(24): 7027–7042. https://doi.org/10.1113/JP287328
  13. Ghayourbabaei F, Farzin M, Keshavarzi Z, Saburi E, Khodadadegan MA, Hajali V (2025) Anxiety-like behaviors in rats exposed to the single and combined program of running exercise and environmental enrichment. Neuroreport 36(1): 31–38. https://doi.org/10.1097/WNR.0000000000002117
  14. Samoilova EM, Baklaushev VP, Belopasov VV (2021) Transcriptional factors of direct neuronal reprogramming in ontogenesis and ex vivo. Mol Biol 55(5): 645–669. https://doi.org/10.1134/S0026893321040087
  15. Khaspekov LG, Frumkina LE (2023) Molecular mechanisms of astrocyte involvement in synaptogenesis and brain synaptic plasticity. Biochemistry (Moscow) 88(4): 502–514. https://doi.org/10.1134/s0006297923040065
  16. Abashkin DA, Karpov DS, Kurishev AO, Marilovtseva EV, Golimbet VE (2023) ASCL1 Is Involved in the Pathogenesis of Schizophrenia by Regulation of Genes Related to Cell Proliferation, Neuronal Signature Formation, and Neuroplasticity. Int J Mol Sci 24(21): 15746. https://doi.org/10.3390/ijms242115746
  17. Soares DS, Homem CCF, Castro DS (2022) Function of Proneural Genes Ascl1 and Asense in Neurogenesis: How Similar Are They? Front Cell Development Biol 10: 838431. https://doi.org/10.3389/fcell.2022.838431
  18. Yamada J, Jinno S (2014) S100А6 (calcyclin) is a novel marker of neural stem cells and astrocyte precursors in the subgranular zone of the adult mouse hippocampus. Hippocampus 24(1): 89–101. https://doi.org/10.1002/hipo.22207
  19. Kjell J, Fischer-Sternjak J, Thompson AJ, Friess C, Sticco MJ, Salinas F, Cox J, Martinelli DC, Ninkovic J, Franze K, Schiller HB, Götz M (2020) Defining the Adult Neural Stem Cell Niche Proteome Identifies Key Regulators of Adult Neurogenesis. Cell Stem Cell 26(2): 277–293.e8. https://doi.org/10.1016/j.stem.2020.01.002
  20. Leśniak W, Filipek A (2023) S100А6 Protein-Expression and Function in Norm and Pathology. Int J Mol Sci 24(2): 1341. https://doi.org/10.3390/ijms24021341
  21. Gu Q, Duan K, Petralia RS, Wang YX, Li Z (2022) BAX regulates dendritic spine development via mitochondrial fusion. Neurosci Res 182: 25–31. https://doi.org/10.1016/j.neures.2022.06.002
  22. Li Z, Sheng M (2012) Caspases in synaptic plasticity. Mol Brain 5: 15. https://doi.org/10.1186/1756-6606-5-15
  23. Kudryashova IV, Kudryashov IE, Gulyaeva NV (2006) Long-term potentiation in the hippocampus in conditions of inhibition of caspase-3: analysis of facilitation in paired-pulse stimulation. Neurosci Behav Physiol 36(8): 817–824. https://doi.org/10.1007/s11055-006-0092-y
  24. Jiang W, Chen L, Zheng S (2021) Global Reprogramming of Apoptosis-Related Genes during Brain Development. Cells 10(11): 2901. https://doi.org/10.3390/cells10112901
  25. Aguilar-Valles A, Sánchez E, de Gortari P, Balderas I, Ramírez-Amaya V, Bermúdez-Rattoni F, Joseph-Bravo P (2005) Analysis of the stress response in rats trained in the water-maze: differential expression of corticotropin-releasing hormone, CRH-R1, glucocorticoid receptors and brain-derived neurotrophic factor in limbic regions. Neuroendocrinology 82(5-6): 306–319. https://doi.org/10.1159/000093129
  26. Carter SD, Mifsud KR, Reul JM (2015) Distinct epigenetic and gene expression changes in rat hippocampal neurons after Morris water maze training. Front Behav Neurosci 9: 156. https://doi.org/10.3389/fnbeh.2015.00156
  27. Gruden MA, Storozheva ZI, Sewell RD, Kolobov VV, Sherstnev VV (2013) Distinct functional brain regional integration of Casp3, Ascl1 and S100А6 gene expression in spatial memory. Behav Brain Res 252: 230–238. https://doi.org/10.1016/j.bbr.2013.06.024
  28. Terry AV, Jr (2009) Spatial Navigation (Water Maze) Tasks. In: Buccafusco (Ed), Methods of Behavior Analysis in Neuroscience. CRC Press/Taylor & Francis.
  29. Paxinos G, Watson C (2007) The Rat Brain in Stereotaxic Coordinates. 6th Edition. Acad Press. San Diego.
  30. Schmittgen TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative C(T) method. Nature Protocol 3(6): 1101–1108. https://doi.org/10.1038/nprot.2008.73
  31. Pei H, Shen H, Bi J, He Z, Zhai L (2024) Gastrodin improves nerve cell injury and behaviors of depressed mice through Caspase-3-mediated apoptosis. CNS Neurosci Therap 30(3): e14444. https://doi.org/10.1111/cns.14444
  32. Parul MA, Singh S, Singh S, Tiwari V, Chaturvedi S, Wahajuddin M, Palit G, Shukla S (2021) Chronic unpredictable stress negatively regulates hippocampal neurogenesis and promote anxious depression-like behavior via upregulating apoptosis and inflammatory signals in adult rats. Brain Res Bull 172: 164–179. https://doi.org/10.1016/j.brainresbull.2021.04.017
  33. Li Y, Han F, Shi Y (2013) Increased neuronal apoptosis in medial prefrontal cortex is accompanied with changes of Bcl-2 and Bax in a rat model of post-traumatic stress disorder. J Mol Neurosci 51(1): 127–137. https://doi.org/10.1007/s12031-013-9965-z
  34. Li X, Han F, Liu D, Shi Y (2010) Changes of Bax, Bcl-2 and apoptosis in hippocampus in the rat model of post-traumatic stress disorder. Neurol Res 32(6): 579–586. https://doi.org/10.1179/016164110X12556180206194
  35. Ahmadian N, Mahmoudi J, Talebi M, Molavi L, Sadigh-Eteghad S, Rostrup E, Ziaee M (2018) Sleep deprivation disrupts striatal anti-apoptotic responses in 6-hydroxy dopamine-lesioned parkinsonian rats. Iran J Basic Med Sci 21(12): 1289–1296. https://doi.org/10.22038/ijbms.2018.28546.6919
  36. Niu Q, Yang Y, Zhang Q, Niu P, He S, Di Gioacchino M, Conti P, Boscolo P (2007) The relationship between Bcl-gene expression and learning and memory impairment in chronic aluminum-exposed rats. Neurotox Res 12(3): 163–169. https://doi.org/10.1007/BF03033913
  37. Miguel-Hidalgo JJ, Paul IA, Wanzo V, Banerjee PK (2012) Memantine prevents cognitive impairment and reduces Bcl-2 and caspase 8 immunoreactivity in rats injected with amyloid β1-40. Eur J Pharmacol 692(1–3): 38–45. https://doi.org/10.1016/j.ejphar.2012.07.032
  38. Harrison FE, Hosseini AH, McDonald MP (2009) Endogenous anxiety and stress responses in water maze and Barnes maze spatial memory tasks. Behav Brain Res 198(1): 247–251. https://doi.org/10.1016/j.bbr.2008.10.015
  39. Crawford LE, Knouse LE, Kent M, Vavra D, Harding O, LeServe D, Fox N, Hu X, Li P, Glory C, Lambert KG (2020) Enriched environment exposure accelerates rodent driving skills. Behav Brain Res 378: 112309. https://doi.org/10.1016/j.bbr.2019.112309
  40. Karishma KK, Herbert J (2002) Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents corticosterone-induced suppression. Eur J Neurosci 16(3): 445–453. https://doi.org/10.1046/j.1460-9568.2002.02099.x
  41. Györffy BA, Kun J, Török G, Bulyáki É, Borhegyi Z, Gulyássy P, Kis V, Szocsics P, Micsonai A, Matkó J, Drahos L, Juhász G, Kékesi KA, Kardos J (2018) Local apoptotic-like mechanisms underlie complement-mediated synaptic pruning. Proceed Natl Acad Sci U S A 115(24): 6303–6308. https://doi.org/10.1073/pnas.1722613115
  42. Gu Q, Jiao S, Duan K, Wang YX, Petralia RS, Li Z (2021) The BAD-BAX-Caspase-3 Cascade Modulates Synaptic Vesicle Pools via Autophagy. J Neurosci 41(6): 1174–1190. https://doi.org/10.1523/JNEUROSCI.0969-20.2020
  43. De Bastiani MA, Bellaver B, Carello-Collar G, Zimmermann M, Kunach P, Lima-Filho RAS, Forner S, Martini AC, Pascoal TA, Lourenco MV, Rosa-Neto P, Zimmer ER (2023) Cross-species comparative hippocampal transcriptomics in Alzheimer's disease. iScience 27(1): 108671. https://doi.org/10.1016/j.isci.2023.108671
  44. Filipek A, Leśniak W (2020) S100А6 and Its Brain Ligands in Neurodegenerative Disorders. Int J Mol Sci 21(11): 3979. https://doi.org/10.3390/ijms21113979
  45. Bartkowska K, Swiatek I, Aniszewska A, Jurewicz E, Turlejski K, Filipek A, Djavadian RL (2017) Stress-Dependent Changes in the CacyBP/SIP Interacting Protein S100А6 in the Mouse Brain. PloS One 12(1): e0169760. https://doi.org/10.1371/journal.pone.0169760
  46. Tian ZY, Wang CY, Wang T, Li YC, Wang ZY (2019) Glial S100А6 Degrades β-amyloid Aggregation through Targeting Competition with Zinc Ions. Aging Disease 10(4): 756–769. https://doi.org/10.14336/AD.2018.0912
  47. Fang B, Liang M, Yang G, Ye Y, Xu H, He X, Huang JH (2014) Expression of S100А6 in rat hippocampus after traumatic brain injury due to lateral head acceleration. Int J Mol Sci 15(4): 6378–6390. https://doi.org/10.3390/ijms15046378
  48. McEwen BS (2001) Plasticity of the hippocampus: adaptation to chronic stress and allostatic load. Ann New York Acad Sci 933: 265–277. https://doi.org/10.1111/j.1749-6632.2001.tb05830.x
  49. Jung S, Choe S, Woo H, Jeong H, An HK, Moon H, Ryu HY, Yeo BK, Lee YW, Choi H, Mun JY, Sun W, Choe HK, Kim EK, Yu SW (2020) Autophagic death of neural stem cells mediates chronic stress-induced decline of adult hippocampal neurogenesis and cognitive deficits. Autophagy16(3): 512–530. https://doi.org/10.1080/15548627.2019.1630222
  50. Uda M, Ishido M, Kami K (2007) Features and a possible role of Mash1-immunoreactive cells in the dentate gyrus of the hippocampus in the adult rat. Brain Res 1171: 9–17. https://doi.org/10.1016/j.brainres.2007.06.099
  51. Oproescu AM, Han S, Schuurmans C (2021) New Insights Into the Intricacies of Proneural Gene Regulation in the Embryonic and Adult Cerebral Cortex. Front Mol Neurosci 14: 642016. https://doi.org/10.3389/fnmol.2021.642016
  52. Zhang RL, Chopp M, Roberts C, Jia L, Wei M, Lu M, Wang X, Pourabdollah S, Zhang ZG (2011) Ascl1 lineage cells contribute to ischemia-induced neurogenesis and oligodendrogenesis. J Cerebr Blood Flow Metabol 31(2): 614–625. https://doi.org/10.1038/jcbfm.2010.134
  53. Faiz M, Sachewsky N, Gascón S, Bang KW, Morshead CM, Nagy A (2015) Adult Neural Stem Cells from the Subventricular Zone Give Rise to Reactive Astrocytes in the Cortex after Stroke. Cell Stem Cell 17(5): 624–634. https://doi.org/10.1016/j.stem.2015.08.002
  54. Su X, Guan W, Yu YC, Fu Y (2014) Cerebellar stem cells do not produce neurons and astrocytes in adult mouse. Biochem Biophys Res Communicat 450(1): 378–383. https://doi.org/10.1016/j.bbrc.2014.05.131
  55. Rusanescu G, Mao J (2017) Peripheral nerve injury induces adult brain neurogenesis and remodelling. J Cell Mol Med 21(2): 299–314. https://doi.org/10.1111/jcmm.12965
  56. Storozheva ZI, Zakharova EI, Proshin AT (2021) Evaluation of the Activity of Choline Acetyltransferase From Different Synaptosomal Fractions at the Distinct Stages of Spatial Learning in the Morris Water Maze. Front Behav Neurosci 15: 755373. https://doi.org/10.3389/fnbeh.2021.755373

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar

Declaração de direitos autorais © Russian Academy of Sciences, 2025