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Possible Engagement of Nicotinic Acetylcholine Receptors in Pathophysiology of Brain Ischemia-Induced Cognitive Impairment

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Abstract

Post-stroke disabilities like cognitive impairment impose are complex conditions with great economic burdens on health care systems. For these comorbidities, no effective therapies have been identified yet. Nicotinic acetylcholine receptors (nAChRs) are multifunctional receptors participating in various behavioral and neurobiological functions. During brain ischemia, the increased glutamate accumulation leads to neuronal excitotoxicity as well as mitochondrial dysfunction. These abnormalities then cause the increased levels of oxidants, which play key roles in neuronal death and apoptosis in the infarct zone. Additionally, recall of cytokines and inflammatory factors play a prominent role in the exacerbation of ischemic injury. As well, neurotrophic factors’ insufficiency results in synaptic dysfunction and cognitive impairments in ischemic brain. Of note, nAChRs through various signaling pathways can participate in therapeutic approaches such as cholinergic system’s stimulation, and reduction of excitotoxicity, inflammation, apoptosis, oxidative stress, mitochondrial dysfunction, and autophagy. Moreover, the possible roles of nAChRs in neurogenesis, synaptogenesis, and stimulation of neurotrophic factors expression have been reported previously. On the other hand, the majority of the above-mentioned mechanisms were found to be common in both brain ischemia pathogenesis and cognitive function tuning. Therefore, it seems that nAChRs might be known as key regulators in the control of ischemia pathology, and their modulation could be considered as a new avenue in the multi-target treatment of post-stroke cognitive impairment.

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References

  • Almli CR, Levy TJ, Han BH, Shah AR, Gidday JM, Holtzman DM (2000) BDNF protects against spatial memory deficits following neonatal hypoxia-ischemia. Exp Neurol 166(1):99–114

    Article  CAS  PubMed  Google Scholar 

  • Andrabi SS, Parvez S, Tabassum H (2020) Ischemic stroke and mitochondria: mechanisms and targets. Protoplasma 257(2):335–343

    Article  PubMed  Google Scholar 

  • Arvidsson A, Collin T, Kirik D, Kokaia Z, Lindvall O (2002) Neuronal replacement from endogenous precursors in the adult brain after stroke. Nat Med 8(9):963–970

    Article  CAS  PubMed  Google Scholar 

  • Atif F, Yousuf S, Sayeed I, Ishrat T, Hua F, Stein DG (2013) Combination treatment with progesterone and vitamin D hormone is more effective than monotherapy in ischemic stroke: the role of BDNF/TrkB/Erk1/2 signaling in neuroprotection. Neuropharmacology 67:78–87

    Article  CAS  PubMed  Google Scholar 

  • Azam NF, Stanyard RA, Mat NH, Hassan Z (2018) Cholinergic modulation of hippocampal long-term potentiation in chronic cerebral hypoperfused rats. Neurosci Res Notes 1(1):42–57

    Article  Google Scholar 

  • Bencherif M (2009) Neuronal nicotinic receptors as novel targets for inflammation and neuroprotection: mechanistic considerations and clinical relevance. Acta Pharmacol Sin 30(6):702–714

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bendel O, Bueters T, von Euler M, Ögren SO, Sandin J, von Euler G (2005) Reappearance of hippocampal CA1 neurons after ischemia is associated with recovery of learning and memory. J Cereb Blood Flow Metab 25(12):1586–1595

    Article  CAS  PubMed  Google Scholar 

  • Boitard C, Cavaroc A, Sauvant J, Aubert A, Castanon N, Layé S et al (2014) Impairment of hippocampal-dependent memory induced by juvenile high-fat diet intake is associated with enhanced hippocampal inflammation in rats. Brain Behav Immun 40:9–17

    Article  CAS  PubMed  Google Scholar 

  • Cechetti F, Worm PV, Elsner VR, Bertoldi K, Sanches E, Ben J et al (2012) Forced treadmill exercise prevents oxidative stress and memory deficits following chronic cerebral hypoperfusion in the rat. Neurobiol Learn Mem 97(1):90–96

    Article  CAS  PubMed  Google Scholar 

  • Chamorro Á, Dirnagl U, Urra X, Planas AM (2016) Neuroprotection in acute stroke: targeting excitotoxicity oxidative and nitrosative stress and inflammation. Lancet Neurol 15(8):869–881

    Article  CAS  PubMed  Google Scholar 

  • Chen A, Xiong L-J, Tong Y, Mao M (2013) The neuroprotective roles of BDNF in hypoxic ischemic brain injury. Biomed Rep 1(2):167–176

    Article  CAS  PubMed  Google Scholar 

  • Chen W, Sun Y, Liu K, Sun X (2014) Autophagy: a double-edged sword for neuronal survival after cerebral ischemia. Neural Regen Res 9(12):1210–1216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen Z-q, Mou R-t, Feng D-x, Wang Z, Chen G (2017) The role of nitric oxide in stroke. Med Gas Res 7(3):194–203

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cordova CA, Jackson D, Langdon KD, Hewlett KA, Corbett D (2014) Impaired executive function following ischemic stroke in the rat medial prefrontal cortex. Behav Brain Res 258:106–111

    Article  PubMed  Google Scholar 

  • Crişan TO, Plantinga TS, van de Veerdonk FL, Farcaş MF, Stoffels M, Kullberg B-J et al (2011) Inflammasome-independent modulation of cytokine response by autophagy in human cells. PloS one 6(4):e18666

  • Czubak A, Nowakowska E, Kus K, Burda K, Metelska J, Baer-Dubowska W et al (2009) Influences of chronic venlafaxine, olanzapine and nicotine on the hippocampal and cortical concentrations of brain-derived neurotrophic factor (BDNF). Pharmacol Rep 61(6):1017–1023

    Article  CAS  PubMed  Google Scholar 

  • Dajas-Bailador FA, Lima PA, Wonnacott S (2000) The α7 nicotinic acetylcholine receptor subtype mediates nicotine protection against NMDA excitotoxicity in primary hippocampal cultures through a Ca2+ dependent mechanism. Neuropharmacology 39(13):2799–2807

    Article  CAS  PubMed  Google Scholar 

  • Damodaran T, Müller CP, Hassan Z (2019) Chronic cerebral hypoperfusion-induced memory impairment and hippocampal long-term potentiation deficits are improved by cholinergic stimulation in rats. Pharmacol Rep 71(3):443–448

    Article  CAS  PubMed  Google Scholar 

  • das Nair R, Cogger H, Worthington E, Lincoln NB (2016) Cognitive rehabilitation for memory deficits after stroke. Cochrane Database Syst Rev 9:CD002293

  • Dawe GB, Yu H, Gu S, Blackler AN, Matta JA, Siuda ER et al (2019) α7 nicotinic acetylcholine receptor upregulation by anti-apoptotic Bcl-2 proteins. Nat Comm 10(1):1–11

    Article  CAS  Google Scholar 

  • De Jonge W, Ulloa L (2007) The alpha7 nicotinic acetylcholine receptor as a pharmacological target for inflammation. Br J Pharmacol 151(7):915–929

    Article  PubMed  PubMed Central  Google Scholar 

  • Degos V, Maze M, Vacas S, Hirsch J, Guo Y, Shen F et al (2013) Bone fracture exacerbates murine ischemic cerebral injury. Anesthesiology 118(6):1362–1372

    Article  CAS  PubMed  Google Scholar 

  • Duan X, Zhang L, Yu J, Wei W, Liu X, Xu F et al (2018) The effect of different frequencies of electroacupuncture on BDNF and NgF expression in the hippocampal ca3 area of the ischemic hemisphere in cerebral ischemic rats. Neuropsychiatr Dis Treat 14:2689–2696

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egea J, Buendia I, Parada E, Navarro E, León R, Lopez MG (2015) Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection. Biochem Pharmacol 97(4):463–472

    Article  CAS  PubMed  Google Scholar 

  • Fan W, Li X, Huang L, He S, Xie Z, Fu Y et al (2018) S-oxiracetam ameliorates ischemic stroke induced neuronal apoptosis through up-regulating α7 nAChR and PI3K/Akt/GSK3β signal pathway in rats. Neurochem Int 115:50–60

    Article  CAS  PubMed  Google Scholar 

  • Ferchmin PA, Perez D, Eterovic VA, de Vellis J (2003) Nicotinic receptors differentially regulate N-methyl-D-aspartate damage in acute hippocampal slices. J Pharmacol Exp Ther 305(3):1071–1078

    Article  CAS  PubMed  Google Scholar 

  • Forner S, Baglietto-Vargas D, Martini AC, Trujillo-Estrada L, LaFerla FM (2017) Synaptic impairment in Alzheimer’s disease: a dysregulated symphony. Trends Neurosci 40(6):347–357

    Article  CAS  PubMed  Google Scholar 

  • Freedman R, Wetmore C, Stromberg I, Leonard S, Olson L (1993) Alpha-bungarotoxin binding to hippocampal interneurons: immunocytochemical characterization and effects on growth factor expression. J Neurosci 13(5):1965–1975

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garrido R, Mattson MP, Hennig B, Toborek M (2001) Nicotine protects against arachidonic-acid-induced caspase activation cytochrome c release and apoptosis of cultured spinal cord neurons. J Neurochem 76(5):1395–1403

    Article  CAS  PubMed  Google Scholar 

  • Gergalova G, Lykhmus O, Kalashnyk O, Koval L, Chernyshov V, Kryukova E et al (2012) Mitochondria express α7 nicotinic acetylcholine receptors to regulate Ca 2+ accumulation and cytochrome c release: study on isolated mitochondria. PloS one 7(2):e31361

  • Gergalova G, Lykhmus O, Komisarenko S, Skok M (2014) α7 nicotinic acetylcholine receptors control cytochrome c release from isolated mitochondria through kinase-mediated pathways. Int J Biochem Cell Biol 49:26–31

    Article  CAS  PubMed  Google Scholar 

  • Gould TJ, Wilkinson DS, Yildirim E, Poole RL, Leach PT, Simmons SJ (2014) Nicotine shifts the temporal activation of hippocampal protein kinase A and extracellular signal-regulated kinase 1/2 to enhance long-term but not short-erm, hippocampus-dependent memory. Neurobiol Learn Mem 109:151–159

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guan Y-Z, Jin X-D, Guan L-X, Yan H-C, Wang P, Gong Z et al (2015) Nicotine inhibits microglial proliferation and is neuroprotective in global ischemia rats. Mol Neurobiol 51(3):1480–1488

    Article  CAS  PubMed  Google Scholar 

  • Guan Z-z (2008) Cross-talk between oxidative stress and modifications of cholinergic and glutaminergic receptors in the pathogenesis of Alzheimer’s disease. Acta Pharmacol Sin 29(7):773–780

    Article  CAS  PubMed  Google Scholar 

  • Guan Z-Z, Yu W-F, Nordberg A (2003) Dual effects of nicotine on oxidative stress and neuroprotection in PC12 cells. Neurochem Int 43(3):243–249

    Article  CAS  PubMed  Google Scholar 

  • Guo F, Lou J, Han X, Deng Y, Huang X (2017) Repetitive transcranial magnetic stimulation ameliorates cognitive impairment by enhancing neurogenesis and suppressing apoptosis in the hippocampus in rats with ischemic stroke. Front Physiol 8:559

    Article  PubMed  PubMed Central  Google Scholar 

  • Han T, Wang Q, Lai R, Zhang D, Diao Y, Yin Y (2020) Nicotine induced neurocognitive protection and anti-inflammation effect by activating α4β2 nAChRs in ischemic rats. Nicotine Tob Res 22:919–924

    Article  CAS  PubMed  Google Scholar 

  • Han Z, Li L, Wang L, Degos V, Maze M, Su H (2014a) Alpha-7 nicotinic acetylcholine receptor agonist treatment reduces neuroinflammation oxidative stress and brain injury in mice with ischemic stroke and bone fracture. J Neurochem 131(4):498–508

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han Z, Shen F, He Y, Degos V, Camus M, Maze M et al (2014b) Activation of α-7 nicotinic acetylcholine receptor reduces ischemic stroke injury through reduction of pro-inflammatory macrophages and oxidative stress. PloS one 9(8):e105711

  • Hejmadi M, Dajas-Bailador F, Barns S, Jones B, Wonnacott S (2003) Neuroprotection by nicotine against hypoxia-induced apoptosis in cortical cultures involves activation of multiple nicotinic acetylcholine receptor subtypes. Mol Cell Neurosci 24(3):779–786

    Article  CAS  PubMed  Google Scholar 

  • Heusch WL, Maneckjee R (1998) Signalling pathways involved in nicotine regulation of apoptosis of human lung cancer cells. Carcinogenesis 19(4):551–556

    Article  CAS  PubMed  Google Scholar 

  • Hofgren C, Björkdahl A, Esbjörnsson E, Stibrant-Sunnerhagen K (2007) Recovery after stroke: cognition, ADL function and return to work. Acta Neurol Scand 115(2):73–80

    Article  CAS  PubMed  Google Scholar 

  • Hota SK, Barhwal K, Ray K, Singh SB, Ilavazhagan G (2008) Ceftriaxone rescues hippocampal neurons from excitotoxicity and enhances memory retrieval in chronic hypobaric hypoxia. Neurobiol Learn Mem 89(4):522–532

    Article  CAS  PubMed  Google Scholar 

  • Hu Y, Chen W, Wu L, Jiang L, Liang N, Tan L et al (2019) TGF-β1 restores hippocampal synaptic plasticity and memory in Alzheimer model via the PI3K/Akt/Wnt/β-catenin signaling pathway. J Mol Neurosci 67(1):142–149

    Article  CAS  PubMed  Google Scholar 

  • Huo T-g, Li W-k, Zhang Y-h, Yuan J, Gao L-y, Yuan Y et al (2015) Excitotoxicity induced by realgar in the rat hippocampus: the involvement of learning memory injury dysfunction of glutamate metabolism and NMDA receptors. Mol Neurobiol 51(3):980–994

    Article  CAS  PubMed  Google Scholar 

  • Janis LS, Glasier MM, Stein DG (1997) Effects of a single intraseptal injection of NGF on spatial learning in the water maze. Physiol Behav 62(1):69–76

    Article  CAS  PubMed  Google Scholar 

  • Ji D, Dani JA (2000) Inhibition and disinhibition of pyramidal neurons by activation of nicotinic receptors on hippocampal interneurons. J Neurophysiol 83(5):2682–2690

    Article  CAS  PubMed  Google Scholar 

  • Jiang Y, Li L, Liu B, Zhang Y, Chen Q, Li C (2014) Vagus nerve stimulation attenuates cerebral ischemia and reperfusion injury via endogenous cholinergic pathway in rat. PLoS One 9(7):e102342

  • Kalaria RN, Ballard C (2001) Stroke and cognition. Curr Atheroscler Rep 3(4):334–339

    Article  CAS  PubMed  Google Scholar 

  • Kita Y, Ago Y, Higashino K, Asada K, Takano E, Takuma K et al (2014) Galantamine promotes adult hippocampal neurogenesis via M1 muscarinic and α 7 nicotinic receptors in mice. Int J Neuropsychopharmacol 17(12):1957–1968

    Article  CAS  PubMed  Google Scholar 

  • Kitamura T, Inokuchi K (2014) Role of adult neurogenesis in hippocampal-cortical memory consolidation. Mol Brain 7(1):1–8

    Article  Google Scholar 

  • Ko I-G, Shin M-S, Kim B-K, Kim S-E, Sung Y-H, Kim T-S et al (2009) Tadalafil improves short-term memory by suppressing ischemia-induced apoptosis of hippocampal neuronal cells in gerbils. Pharmacol Biochem Behav 91(4):629–635

    Article  CAS  PubMed  Google Scholar 

  • Ko C-H, Huang C-P, Lin Y-W, Hsieh C-L (2018) Paeoniflorin has anti-inflammation and neurogenesis functions through nicotinic acetylcholine receptors in cerebral ischemia-reperfusion injury rats. Iran J Basic Med Sci 21(11):1174

    PubMed  PubMed Central  Google Scholar 

  • Li Y, King MA, Meyer EM (2000) α7 nicotinic receptor-mediated protection against ethanol-induced oxidative stress and cytotoxicity in PC12 cells. Brain Res 861(1):165–167

    Article  CAS  PubMed  Google Scholar 

  • Li WL, Cai HH, Wang B, Chen L, Zhou QG, Luo CX et al (2009) Chronic fluoxetine treatment improves ischemia-induced spatial cognitive deficits through increasing hippocampal neurogenesis after stroke. J Neurosci Res 87(1):112–122

    Article  CAS  PubMed  Google Scholar 

  • Li Z, Wang J, Zhao C, Ren K, Xia Z, Yu H et al (2016) Acute blockage of notch signaling by DAPT induces neuroprotection and neurogenesis in the neonatal rat brain after stroke. Transl Stroke Res 7(2):132–140

    Article  CAS  PubMed  Google Scholar 

  • Liu Q, Zhao B (2004) Nicotine attenuates β-amyloid peptide-induced neurotoxicity, free radical and calcium accumulation in hippocampal neuronal cultures. Br J Pharmacol 141(4):746–754

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu Z, Fan Y, Won SJ, Neumann M, Hu D, Zhou L et al (2007) Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia. Stroke 38(1):146–152

    Article  CAS  PubMed  Google Scholar 

  • Liu Y, Zeng X, Hui Y, Zhu C, Wu J, Taylor DH et al (2015a) Activation of α7 nicotinic acetylcholine receptors protects astrocytes against oxidative stress-induced apoptosis: implications for Parkinson’s disease. Neuropharmacology 91:87–96

    Article  CAS  PubMed  Google Scholar 

  • Liu P, Zhao H, Wang R, Wang P, Tao Z, Gao L et al (2015b) MicroRNA-424 protects against focal cerebral ischemia and reperfusion injury in mice by suppressing oxidative stress. Stroke 46(2):513–519

    Article  CAS  PubMed  Google Scholar 

  • Liu W-J, Jiang H-F, Rehman FU, Zhang J-W, Chang Y, Jing L et al (2017) Lycium barbarum polysaccharides decrease hyperglycemia-aggravated ischemic brain injury through maintaining mitochondrial fission and fusion balance. Int J Biol Sci 13(7):901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liu H, Zhong L, Zhang Y, Liu X, Li J (2018) Rutin attenuates cerebral ischemia–reperfusion injury in ovariectomized rats via estrogen-receptor-mediated BDNF–TrkB and NGF–TrkA signaling. Biochem Cell Biol 96(5):672–681

    Article  CAS  PubMed  Google Scholar 

  • Livingston-Thomas JM, Jeffers MS, Nguemeni C, Shoichet MS, Morshead CM, Corbett D (2015) Assessing cognitive function following medial prefrontal stroke in the rat. Behav Brain Res 294:102–110

    Article  PubMed  Google Scholar 

  • Lo EH (2009) T time in the brain. Nat Med 15(8):844

    Article  CAS  PubMed  Google Scholar 

  • Lu L, Guo L, Gauba E, Tian J, Wang L, Tandon N et al (2015) Transient cerebral ischemia promotes brain mitochondrial dysfunction and exacerbates cognitive impairments in young 5xFAD mice. PloS one 10(12):e0144068

  • Lu Y, Jiang L, Li W, Qu M, Song Y, He X et al (2017) Optogenetic inhibition of striatal neuronal activity improves the survival of transplanted neural stem cells and neurological outcomes after ischemic stroke in mice. Stem Cells Int 2017:1–11

    CAS  Google Scholar 

  • Lykhmus O, Gergalova G, Koval L, Zhmak M, Komisarenko S, Skok M (2014) Mitochondria express several nicotinic acetylcholine receptor subtypes to control various pathways of apoptosis induction. Int J Biochem Cell Biol 53:246–252

    Article  CAS  PubMed  Google Scholar 

  • Majdi A, Kamari F, Vafaee MS, Sadigh-Eteghad S (2017) Revisiting nicotine’s role in the ageing brain and cognitive impairment. Rev Neurosci 28(7):767–781

    Article  CAS  PubMed  Google Scholar 

  • Majdi A, Kamari F, Sadigh-Eteghad S, Gjedde A (2018) Molecular insights into memory-enhancing metabolites of nicotine in brain: a systematic review. Front Neurosci 12:1–11

    Google Scholar 

  • Malenka RC, Nicoll RA (1999) Long-term potentiation—a decade of progress? Science 285(5435):1870–1874

    Article  CAS  PubMed  Google Scholar 

  • Marzolini S, Oh P, McIlroy W, Brooks D (2013) The effects of an aerobic and resistance exercise training program on cognition following stroke. Neurorehabil Neural Repair 27(5):392–402

    Article  PubMed  Google Scholar 

  • Mazereeuw G, Herrmann N, Andreazza AC, Scola G, Ma DW, Oh PI et al (2017) Baseline oxidative stress is associated with memory changes in omega-3 fatty acid treated coronary artery disease patients. Cardiovasc Psychiatry Neurol 2017:1–7

    Article  Google Scholar 

  • McKay BE, Placzek AN, Dani JA (2007) Regulation of synaptic transmission and plasticity by neuronal nicotinic acetylcholine receptors. Biochem Pharmacol 74(8):1120–1133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Min D, Mao X, Wu K, Cao Y, Guo F, Zhu S et al (2012) Donepezil attenuates hippocampal neuronal damage and cognitive deficits after global cerebral ischemia in gerbils. Neurosci Lett 510(1):29–33

    Article  CAS  PubMed  Google Scholar 

  • Mitsis EM, Cosgrove KP, Staley JK, Bois F, Frohlich EB, Tamagnan GD et al (2009) Age-related decline in nicotinic receptor availability with [123I] 5-IA-85380 SPECT. Neurobiol Aging 30(9):1490–1497

    Article  CAS  PubMed  Google Scholar 

  • Nakauchi S, Sumikawa K (2012) Endogenously released ACh and exogenous nicotine differentially facilitate long-term potentiation induction in the hippocampal CA1 region of mice. Eur J Neurosci 35(9):1381–1395

    Article  PubMed  Google Scholar 

  • Narla S, Klejbor I, Birkaya B, Lee Y-W, Morys J, Stachowiak EK et al (2013a) α7 nicotinic receptor agonist reactivates neurogenesis in adult brain. Biochem Pharmacol 86(8):1099–1104

    Article  CAS  PubMed  Google Scholar 

  • Narla ST, Klejbor I, Birkaya B, Lee Y-W, Morys J, Stachowiak EK et al (2013b) Activation of developmental nuclear fibroblast growth factor receptor 1 signaling and neurogenesis in adult brain by α7 nicotinic receptor agonist. Stem Cells Transl Med 2(10):776–788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nikiforuk A, Litwa E, Krawczyk M, Popik P, Arias H (2020) Desformylflustrabromine a positive allosteric modulator of α4β2-containing nicotinic acetylcholine receptors enhances cognition in rats. Pharmacol Rep 72(3):589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nishiyama J, Yuzaki M (2010) Excitotoxicity and autophagy: Lurcher may not be a model of “autophagic cell death.” Autophagy 6(4):568–570

    Article  PubMed  Google Scholar 

  • Otto SL, Yakel JL (2019) The α7 nicotinic acetylcholine receptors regulate hippocampal adult-neurogenesis in a sexually dimorphic fashion. Brain Struct Funct 224(2):829–846

    Article  PubMed  Google Scholar 

  • Paez-Gonzalez P, Asrican B, Rodriguez E, Kuo CT (2014) Identification of distinct ChAT+ neurons and activity-dependent control of postnatal SVZ neurogenesis. Nat Neurosci 17(7):934–942

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Patki G, Solanki N, Atrooz F, Allam F, Salim S (2013) Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress. Brain Res 1539:73–86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Picciotto MR, Zoli M (2002) Nicotinic receptors in aging and dementia. J Neurobiol 53(4):641–655

    Article  CAS  PubMed  Google Scholar 

  • Potasiewicz A, Golebiowska J, Popik P, Nikiforuk A (2019) Procognitive effects of varenicline in the animal model of schizophrenia depend on α4β2-and α7-nicotinic acetylcholine receptors. J Psychopharmacol 33(1):62–73

    Article  CAS  Google Scholar 

  • Pratt BM, McPherson JM (1997) TGF-β in the central nervous system: potential roles in ischemic injury and neurodegenerative diseases. Cytokine Growth Factor Rev 8(4):267–292

    Article  CAS  PubMed  Google Scholar 

  • Raber J, Fan Y, Matsumori Y, Liu Z, Weinstein PR, Fike JR et al (2004) Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits. Ann Neurol 55(3):381–389

    Article  PubMed  Google Scholar 

  • Rama R, García JC (2016) Excitotoxicity and oxidative stress in acute stroke. Ischemic Stroke-Updates Intech 17–42

  • Ray R, Rai S, Katyal A (2014) Cholinergic receptor blockade by scopolamine and mecamylamine exacerbates global cerebral ischemia induced memory dysfunction in C57BL/6J mice. Nitric Oxide 43:62–73

    Article  CAS  PubMed  Google Scholar 

  • Roberts JP, Stokoe SA, Sathler MF, Nichols RA, Kim S (2021) Selective coactivation of α7-and α4β2-nicotinic acetylcholine receptors reverses beta-amyloid–induced synaptic dysfunction. J Biol Chem 296:100402

  • Schilling M, Besselmann M, Müller M, Strecker JK, Ringelstein EB, Kiefer R (2005) Predominant phagocytic activity of resident microglia over hematogenous macrophages following transient focal cerebral ischemia: an investigation using green fluorescent protein transgenic bone marrow chimeric mice. Exp Neurol 196(2):290–297

    Article  CAS  PubMed  Google Scholar 

  • Schurr A (2002) Lactate, glucose and energy metabolism in the ischemic brain. Int J Mol Med 10(2):131–136

    CAS  PubMed  Google Scholar 

  • Shabani Z, Mahmoudi J, Farajdokht F, Sadigh-Eteghad S (2020) An overview of nicotinic cholinergic system signaling in neurogenesis. Arch Med Res 51:287–296

    Article  CAS  PubMed  Google Scholar 

  • Shao B-Z, Ke P, Xu Z-Q, Wei W, Cheng M-H, Han B-Z et al (2017) Autophagy plays an important role in anti-inflammatory mechanisms stimulated by alpha7 nicotinic acetylcholine receptor. Front Immunol 8:553

    Article  PubMed  PubMed Central  Google Scholar 

  • Shen H, Kihara T, Hongo H, Wu X, Kem W, Shimohama S et al (2010) Neuroprotection by donepezil against glutamate excitotoxicity involves stimulation of α7 nicotinic receptors and internalization of NMDA receptors. Br J Pharmacol 161(1):127–139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimazu K, Zhao M, Sakata K, Akbarian S, Bates B, Jaenisch R et al (2006) NT-3 facilitates hippocampal plasticity and learning and memory by regulating neurogenesis. Learn Mem 13(3):307–315

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shimohama S, Greenwald D, Shafron D, Akaika A, Maeda T, Kaneko S et al (1998) Nicotinic α7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage. Brain Res 779(1–2):359–363

    Article  CAS  PubMed  Google Scholar 

  • Skaper SD (2018) Neurotrophic factors: an overview. Neurotrophic Factors 1–17

  • Skok M, Gergalova G, Lykhmus O, Kalashnyk O, Koval L, Uspenska K (2016) Nicotinic acetylcholine receptors in mitochondria: subunit composition function and signaling. Neurotransmitter 3

  • Son J-H, Winzer-Serhan UH (2009) Chronic neonatal nicotine exposure increases mRNA expression of neurotrophic factors in the postnatal rat hippocampus. Brain Res 1278:1–14

    Article  CAS  PubMed  Google Scholar 

  • Soto-Otero R, Méndez-Álvarez E, Hermida-Ameijeiras Á, López-Real AM, Labandeira-Garcı́a JL (2002) Effects of (−)-nicotine and (−)-cotinine on 6-hydroxydopamine-induced oxidative stress and neurotoxicity: relevance for Parkinson’s disease. Biochem Pharmacol 64(1):125–135

    Article  CAS  PubMed  Google Scholar 

  • Stradecki-Cohan HM, Cohan CH, Raval AP, Dave KR, Reginensi D, Gittens RA et al (2017) Cognitive deficits after cerebral ischemia and underlying dysfunctional plasticity: potential targets for recovery of cognition. J Alzheimers Dis 60(s1):S87–S105

    Article  PubMed  Google Scholar 

  • Su S-Y, Cheng C-Y, Tsai T-H, Hsieh C-L (2012) Paeonol protects memory after ischemic stroke via inhibiting β-secretase and apoptosis. Evid Based Complement Alternat Med 2012:1–11

    Google Scholar 

  • Suárez-Pereira I, Carrión ÁM (2015) Updating stored memory requires adult hippocampal neurogenesis. Sci Rep 5:13993

    Article  PubMed  PubMed Central  Google Scholar 

  • Tang EY, Amiesimaka O, Harrison SL, Green E, Price C, Robinson L et al (2018) Longitudinal effect of stroke on cognition: a systematic review. J Am Heart Assoc 7(2):e006443

  • Terry AV Jr, Callahan PM (2019) Nicotinic acetylcholine receptor ligands, cognitive function, and preclinical approaches to drug discovery. Nicotine Tob Res 21(3):383–394

    Article  PubMed  Google Scholar 

  • Tizabi Y, Manaye KF, Taylor RE (2005) Nicotine blocks ethanol-induced apoptosis in primary cultures of rat cerebral cortical and cerebellar granule cells. Neurotox Res 7(4):319

    Article  CAS  PubMed  Google Scholar 

  • Toescu EC, Verkhratsky A, Landfield PW (2004) Ca2+ regulation and gene expression in normal brain aging. Trends Neurosci 27(10):614–620

    Article  CAS  PubMed  Google Scholar 

  • Tortora M, Corsini S, Nistri A (2017) Nicotinic receptors modulate the onset of reactive oxygen species production and mitochondrial dysfunction evoked by glutamate uptake block in the rat hypoglossal nucleus. Neurosci Lett 639:43–48

    Article  CAS  PubMed  Google Scholar 

  • Townsend M, Whyment A, Walczak J-S, Jeggo R, van den Top M, Flood DG et al (2016) α7-nAChR agonist enhances neural plasticity in the hippocampus via a GABAergic circuit. J Neurophysiol 116(6):2663–2675

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G et al (2008) Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J 27(2):433–446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Verma R, Harris NM, Friedler BD, Crapser J, Patel AR, Venna V et al (2016) Reversal of the detrimental effects of post-stroke social isolation by pair-housing is mediated by activation of BDNF-MAPK/ERK in aged mice. Sci Rep 6(1):1–13

    Article  Google Scholar 

  • Wang Y, Wu C, Han B, Xu F, Mao M, Guo X et al (2016) Dexmedetomidine attenuates repeated propofol exposure-induced hippocampal apoptosis, PI3K/Akt/Gsk-3β signaling disruption, and juvenile cognitive deficits in neonatal rats. Mol Med Rep 14(1):769–775

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang J, Fu X, Zhang D, Yu L, Li N, Lu Z et al (2017a) ChAT-positive neurons participate in subventricular zone neurogenesis after middle cerebral artery occlusion in mice. Behav Brain Res 316:145–151

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Lu Z, Fu X, Zhang D, Yu L, Li N et al (2017b) Alpha-7 nicotinic receptor signaling pathway participates in the neurogenesis induced by ChAT-positive neurons in the subventricular zone. Transl Stroke Res 8(5):484–493

    Article  CAS  Google Scholar 

  • Wang J, Zhang S, Ma H, Yang S, Liu Z, Wu X et al (2017c) Chronic intermittent hypobaric hypoxia pretreatment ameliorates ischemia-induced cognitive dysfunction through activation of ERK1/2-CREB-BDNF pathway in anesthetized mice. Neurochem Res 42(2):501–512

    Article  CAS  PubMed  Google Scholar 

  • Ward R, Valenzuela JP, Li W, Dong G, Fagan SC, Ergul A (2018) Poststroke cognitive impairment and hippocampal neurovascular remodeling: the impact of diabetes and sex. Am J Physiol Heart Circ Physiol 315(5):H1402–H1413

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu B, Zhu L, Chu J, Ma Z, Fu Q, Wei W et al (2019) Esculetin improves cognitive impairments induced by transient cerebral ischaemia and reperfusion in mice via regulation of mitochondrial fragmentation and mitophagy. Behav Brain Res 372:112007

  • Yabuki Y, Fukunaga K (2013) Oral administration of glutathione improves memory deficits following transient brain ischemia by reducing brain oxidative stress. Neuroscience 250:394–407

    Article  CAS  PubMed  Google Scholar 

  • Yang J-L, Mukda S, Chen S-D (2018) Diverse roles of mitochondria in ischemic stroke. Redox Biol 16:263–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yu W, Mechawar N, Krantic S, Quirion R (2011) α7 Nicotinic receptor activation reduces β-amyloid-induced apoptosis by inhibiting caspase-independent death through phosphatidylinositol 3-kinase signaling. J Neurochem 119(4):848–858

    Article  CAS  PubMed  Google Scholar 

  • Yu Y, Feng L, Li J, Lan X, Lixiang A, Lv X et al (2017) The alteration of autophagy and apoptosis in the hippocampus of rats with natural aging-dependent cognitive deficits. Behav Brain Res 334:155–162

    Article  CAS  PubMed  Google Scholar 

  • Yuan M, Zhang X-X, Fu X-C, Bi X (2020) Enriched environment alleviates post-stroke cognitive impairment through enhancing α7-nAChR expression in rats. Arq Neuro-Psiquiatr 78(10):603–610

    Article  Google Scholar 

  • Zhang W, Cheng J, Vagnerova K, Ivashkova Y, Young J, Cornea A et al (2014) Effects of androgens on early post-ischemic neurogenesis in mice. Transl Stroke Res 5(2):301–311

    Article  CAS  PubMed  Google Scholar 

  • Zhang Y, Yu P, Liu H, Yao H, Yao S, Yuan S et al (2019) Hyperforin improves post-stroke social isolationinduced exaggeration of PSD and PSA via TGF-β. Int J Mol Med 43(1):413–425

    PubMed  Google Scholar 

  • Zheng L, Ding J, Wang J, Zhou C, Zhang W (2016) Effects and mechanism of action of inducible nitric oxide synthase on apoptosis in a rat model of cerebral ischemia-reperfusion injury. Anat Rec 299(2):246–255

    Article  CAS  Google Scholar 

  • Zhou S, Qiao B, Chu X, Kong Q (2018) Oxymatrine attenuates cognitive deficits through SIRT1-mediated autophagy in ischemic stroke. J Neuroimmunol 323:136–142

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors would like to thank NSRC and TUOMS for supporting this research.

Funding

Research reported in this publication was supported by a grant received from Neurosciences Research Center, Tabriz University of Medical Sciences (award number 64417).

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Authors and Affiliations

  1. Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Fatemehsadat Seyedaghamiri, Javad Mahmoudi, Leila Hosseini, Saeed Sadigh-Eteghad & Mehdi Farhoudi

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  1. Fatemehsadat Seyedaghamiri
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  2. Javad Mahmoudi
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  3. Leila Hosseini
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  4. Saeed Sadigh-Eteghad
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  5. Mehdi Farhoudi
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All authors have contributed to writing the manuscript, conceiving the idea, designing the study, and editing the manuscript.

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Correspondence to Saeed Sadigh-Eteghad or Mehdi Farhoudi.

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Seyedaghamiri, F., Mahmoudi, J., Hosseini, L. et al. Possible Engagement of Nicotinic Acetylcholine Receptors in Pathophysiology of Brain Ischemia-Induced Cognitive Impairment. J Mol Neurosci 72, 642–652 (2022). https://doi.org/10.1007/s12031-021-01917-4

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