Skip to main content
SpringerLink
Log in

Regulation of Neurogenesis by Organic Cation Transporters: Potential Therapeutic Implications

  • Chapter
  • First Online:
Organic Cation Transporters in the Central Nervous System

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 266))

Abstract

Neurogenesis is the process by which new neurons are generated from neural stem cells (NSCs), which are cells that have the ability to proliferate and differentiate into neurons, astrocytes, and oligodendrocytes. The process is essential for homeostatic tissue regeneration and the coordination of neural plasticity throughout life, as neurons cannot regenerate once injured. Therefore, defects in neurogenesis are related to the onset and exacerbation of several neuropsychiatric disorders, and therefore, the regulation of neurogenesis is considered to be a novel strategy for treatment. Neurogenesis is regulated not only by NSCs themselves, but also by the functional microenvironment surrounding the NSCs, known as the “neurogenic niche.” The neurogenic niche consists of several types of neural cells, including neurons, glial cells, and vascular cells. To allow communication with these cells, transporters may be involved in the secretion and uptake of substrates that are essential for signal transduction. This chapter will focus on the involvement of polyspecific solute carriers transporting organic cations in the possible regulation of neurogenesis by controlling the concentration of several organic cation substrates in NSCs and the neurogenic niche. The potential therapeutic implications of neurogenesis regulation by these transporters will also be discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abe H, Jitsuki S, Nakajima W et al (2018) CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage. Science 360:50–57

    Article  CAS  PubMed  Google Scholar 

  • Ahmed S, Mahmood Z, Javed A et al (2017) Effect of metformin on adult hippocampal neurogenesis: comparison with donepezil and links to cognition. J Mol Neurosci 62:88–98

    Article  CAS  PubMed  Google Scholar 

  • Alam MJ, Kitamura T, Saitoh Y et al (2018) Adult neurogenesis conserves hippocampal memory capacity. J Neurosci 38:6854–6863

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Athanassakis I, Zarifi I, Evangeliou A, Vassiliadis S (2002) L-Carnitine accelerates the in vitro regeneration of neural network from adult murine brain cells. Brain Res 932:70–78

    Article  CAS  PubMed  Google Scholar 

  • Backhouse B, Barochovsky O, Malik C et al (1982) Effects of haloperidol on cell proliferation in the early postnatal rat brain. Neuropathol Appl Neurobiol 8:109–116

    Article  CAS  PubMed  Google Scholar 

  • Bacq A, Balasse L, Biala G et al (2012) Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response. Mol Psychiatry 17:926–939

    Article  CAS  PubMed  Google Scholar 

  • Baganz NL, Horton RE, Calderon AS et al (2008) Organic cation transporter 3: keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice. Proc Natl Acad Sci U S A 105:18976–18981

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Banasr M, Hery M, Printemps R, Daszuta A (2004) Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharmacology 29:450–460

    Article  CAS  PubMed  Google Scholar 

  • Bátiz LF, Castro MA, Burgos PV et al (2016) Exosomes as novel regulators of adult neurogenic niches. Front Cell Neurosci 9:501

    Article  PubMed  PubMed Central  Google Scholar 

  • Benninghoff J, Van Der Ven A, Schloesser RJ et al (2012) The complex role of the serotonin transporter in adult neurogenesis and neuroplasticity. A critical review. World J Biol Psychiatry 13:240–247

    Article  PubMed  Google Scholar 

  • Bonzano S, Crisci I, Podlesny-Drabiniok A et al (2018) Neuron-Astroglia cell fate decision in the adult mouse hippocampal neurogenic niche is cell-intrinsically controlled by COUP-TFI in vivo. Cell Rep 24:329–341

    Article  CAS  PubMed  Google Scholar 

  • Brazel CY, Rao MS (2004) Aging and neuronal replacement. Ageing Res Rev 3:465–483

    Article  PubMed  Google Scholar 

  • Busch AE, Karbach U, Miska D et al (1998) Human neurons express the polyspecific cation transporter hOCT2, which translocates monoamine neurotransmitters, amantadine, and memantine. Mol Pharmacol 54:342–352

    Article  CAS  PubMed  Google Scholar 

  • Cameron HA, McEwen BS, Gould E (1995) Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus. J Neurosci 15:4687–4692

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Campbell JM, Stephenson MD, de Courten B et al (2018) Metformin use associated with reduced risk of dementia in patients with diabetes: a systematic review and meta-analysis. J Alzheimers Dis 65:1225–1236

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheah IK, Feng L, Tang RMY et al (2016) Ergothioneine levels in an elderly population decrease with age and incidence of cognitive decline; a risk factor for neurodegeneration? Biochem Biophys Res Commun 478:162–167

    Article  CAS  PubMed  Google Scholar 

  • Clarke M, Razmjou S, Prowse N et al (2017) Ketamine modulates hippocampal neurogenesis and pro-inflammatory cytokines but not stressor induced neurochemical changes. Neuropharmacology 112:210–220

    Article  CAS  PubMed  Google Scholar 

  • Cope EC, Gould E (2019) Adult neurogenesis, glia, and the extracellular matrix. Cell Stem Cell 24:690–705

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Couroussé T, Gautron S (2015) Role of organic cation transporters (OCTs) in the brain. Pharmacol Ther 146:94–103

    Article  PubMed  Google Scholar 

  • Cuccurazzu B, Bortolotto V, Valente MM et al (2013) Upregulation of mGlu2 receptors via NF-κB p65 acetylation is involved in the proneurogenic and antidepressant effects of acetyl-L-carnitine. Neuropsychopharmacology 38:2220–2230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daws LC (2009) Unfaithful neurotransmitter transporters: focus on serotonin uptake and implications for antidepressant efficacy. Pharmacol Ther 121:89–99

    Article  CAS  PubMed  Google Scholar 

  • Eisch AJ, Petrik D (2012) Depression and hippocampal neurogenesis: a road to remission? Science 338:72–75

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Engel K, Zhou M, Wang J (2004) Identification and characterization of a novel monoamine transporter in the human brain. J Biol Chem 279:50042–50049

    Article  CAS  PubMed  Google Scholar 

  • Fathi E, Farahzadi R, Charoudeh HN (2017) L-carnitine contributes to enhancement of neurogenesis from mesenchymal stem cells through Wnt/β-catenin and PKA pathway. Exp Biol Med 242:482–486

    Article  CAS  Google Scholar 

  • Fava M, Johe K, Ereshefsky L et al (2016) A phase 1B, randomized, double blind, placebo controlled, multiple-dose escalation study of NSI-189 phosphate, a neurogenic compound, in depressed patients. Mol Psychiatry 21:1372–1380

    Article  CAS  PubMed  Google Scholar 

  • Frigeni M, Balakrishnan B, Yin X et al (2017) Functional and molecular studies in primary carnitine deficiency. Hum Mutat 38:1684–1699

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fukushima T, Nakamura A, Iwakami N et al (2011) T-817MA, a neuroprotective agent, attenuates the motor and cognitive impairments associated with neuronal degeneration in P301L tau transgenic mice. Biochem Biophys Res Commun 407:730–734

    Article  CAS  PubMed  Google Scholar 

  • Gasser PJ, Hurley MM, Chan J et al (2017) Organic cation transporter 3 (OCT3) is localized to intracellular and surface membranes in select glial and neuronal cells within the basolateral amygdaloid complex of both rats and mice. Brain Struct Funct 222:1913–1928

    Article  CAS  PubMed  Google Scholar 

  • Guo M, Mi J, Jiang QM et al (2014) Metformin may produce antidepressant effects through improvement of cognitive function among depressed patients with diabetes mellitus. Clin Exp Pharmacol Physiol 41:650–656

    CAS  PubMed  Google Scholar 

  • Gur TL, Conti AC, Holden J et al (2007) cAMP response element-binding protein deficiency allows for increased neurogenesis and a rapid onset of antidepressant response. J Neurosci 27:7860–7868

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Han X, Tong J, Zhang J et al (2011) Imipramine treatment improves cognitive outcome associated with enhanced hippocampal neurogenesis after traumatic brain injury in mice. J Neurotrauma 28:995–1007

    Article  PubMed  PubMed Central  Google Scholar 

  • Hatano T, Saiki S, Okuzumi A et al (2016) Identification of novel biomarkers for Parkinson’s disease by Metabolomic technologies. J Neurol Neurosurg Psychiatry 87:295–301

    Article  PubMed  Google Scholar 

  • Herculano-Houzel S, Mota B, Lent R (2006) Cellular scaling rules for rodent brains. Proc Natl Acad Sci U S A 103:12138–12143

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Höglinger GU, Rizk P, Muriel MP et al (2004) Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci 7:726–735

    Article  PubMed  Google Scholar 

  • Horton RE, Apple DM, Owens WA et al (2013) Decynium-22 enhances SSRI-induced antidepressant-like effects in mice: uncovering novel targets to treat depression. J Neurosci 33:10534–10543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Inazu M, Takeda H, Maehara K et al (2006) Functional expression of the organic cation/carnitine transporter 2 in rat astrocytes. J Neurochem 97:424–434

    Article  CAS  PubMed  Google Scholar 

  • Ishimoto T, Nakamichi N, Hosotani H et al (2014) Organic cation transporter-mediated ergothioneine uptake in mouse neural progenitor cells suppresses proliferation and promotes differentiation into neurons. PLoS One 9:e89434

    Article  PubMed  PubMed Central  Google Scholar 

  • Ishimoto T, Nakamichi N, Nishijima H et al (2018) Carnitine/organic cation transporter OCTN1 negatively regulates activation in murine cultured microglial cells. Neurochem Res 43:107–119

    Article  Google Scholar 

  • Ishimoto T, Masuo Y, Kato Y, Nakamichi N (2019) Ergothioneine-induced neuronal differentiation is mediated through activation of S6K1 and neurotrophin 4/5-TrkB signaling in murine neural stem cells. Cell Signal 53:269–280

    Article  CAS  PubMed  Google Scholar 

  • Januszewicz E, Bekisz M, Mozrzymas JW, Nałecz KA (2010) High affinity carnitine transporters from OCTN family in neural cells. Neurochem Res 35:743–748

    Article  CAS  PubMed  Google Scholar 

  • Jha S, Rajendran R, Davda J, Vaidya VA (2006) Selective serotonin depletion does not regulate hippocampal neurogenesis in the adult rat brain: differential effects of p-chlorophenylalanine and 5,7-dihydroxytryptamine. Brain Res 1075:48–59

    Article  CAS  PubMed  Google Scholar 

  • Johansson CB, Momma S, Clarke DL et al (1999) Identification of a neural stem cell in the adult mammalian central nervous system. Cell 96:25–34

    Article  CAS  PubMed  Google Scholar 

  • Kato Y, Kubo Y, Iwata D et al (2010) Gene knockout and metabolome analysis of carnitine/organic cation transporter OCTN1. Pharm Res 27:832–840

    Article  CAS  PubMed  Google Scholar 

  • Keiser M, Hasan M, Oswald S (2018) Affinity of ketamine to clinically relevant transporters. Mol Pharm 15:326–331

    Article  CAS  PubMed  Google Scholar 

  • Kido Y, Tamai I, Ohnari A et al (2001) Functional relevance of carnitine transporter OCTN2 to brain distribution of L-camitine and acetyl-L-carnitine across the blood-brain barrier. J Neurochem 79:959–969

    Article  CAS  PubMed  Google Scholar 

  • Kim DK, Tolliver TJ, Huang SJ et al (2005) Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter. Neuropharmacology 49:798–810

    Article  CAS  PubMed  Google Scholar 

  • Kim HJ, Shaker MR, Cho B et al (2015) Dynamin-related protein 1 controls the migration and neuronal differentiation of subventricular zone-derived neural progenitor cells. Sci Rep 5:15962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kimura S, Amemiya F (1990) Brain and liver pathology in a patient with carnitine deficiency. Brain Dev 12:436–439

    Article  CAS  PubMed  Google Scholar 

  • Klempin F, Babu H, De Pietri TD et al (2010) Oppositional effects of serotonin receptors 5-HT1a, 2, and 2c in the regulation of adult hippocampal neurogenesis. Front Mol Neurosci 3:14

    PubMed  PubMed Central  Google Scholar 

  • Knoth R, Singec I, Ditter M et al (2010) Murine features of neurogenesis in the human hippocampus across the lifespan from 0 to 100 years. PLoS One 5:e8809

    Article  PubMed  PubMed Central  Google Scholar 

  • Kohl Z, Winner B, Ubhi K et al (2012) Fluoxetine rescues impaired hippocampal neurogenesis in a transgenic A53T synuclein mouse model. Eur J Neurosci 35:10–19

    Article  PubMed  PubMed Central  Google Scholar 

  • Kraus C, Rabl U, Vanicek T et al (2017) Administration of ketamine for unipolar and bipolar depression. Int J Psychiatry Clin Pract 21:2–12

    Article  CAS  PubMed  Google Scholar 

  • Kumar A, Pareek V, Faiq MA et al (2019) Adult neurogenesis in humans: a review of basic concepts, history, current research, and clinical implications. Innov Clin Neurosci 16:30–37

    CAS  PubMed  PubMed Central  Google Scholar 

  • LaDage LD (2015) Environmental change, the stress response, and neurogenesis. Integr Comp Biol 59:243–250

    Google Scholar 

  • Lamhonwah AM, Hawkins CE, Tam C et al (2008) Expression patterns of the organic cation/carnitine transporter family in adult murine brain. Brain Dev 30:31–42

    Article  PubMed  Google Scholar 

  • Le Grand JN, Gonzalez-Cano L, Pavlou MA, Schwamborn JC (2015) Neural stem cells in Parkinson’s disease: a role for neurogenesis defects in onset and progression. Cell Mol Life Sci 72:773–797

    Article  PubMed  Google Scholar 

  • Lehtinen MK, Zappaterra MW, Chen X et al (2011) The cerebrospinal fluid provides a proliferative niche for neural progenitor cells. Neuron 69:893–905

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Luikart BW, Birnbaum S et al (2008) TrkB regulates hippocampal neurogenesis and governs sensitivity to antidepressive treatment. Neuron 59:399–412

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li B, Gu L, Hertz L, Peng L et al (2013) Expression of nucleoside transporter in freshly isolated neurons and astrocytes from mouse brain. Neurochem Res 38:2351–2358

    Article  CAS  PubMed  Google Scholar 

  • Lin R, Cai J, Kenyon L et al (2019) Systemic factors trigger vasculature cells to drive notch signaling and neurogenesis in neural stem cells in the adult brain. Stem Cells 37:395–406

    Article  PubMed  Google Scholar 

  • Maekawa M, Namba T, Suzuki E et al (2009) NMDA receptor antagonist memantine promotes cell proliferation and production of mature granule neurons in the adult hippocampus. Neurosci Res 63:259–266

    Article  CAS  PubMed  Google Scholar 

  • Malynn S, Campos-Torres A, Moynagh P, Haase J (2013) The pro-inflammatory cytokine TNF-α regulates the activity and expression of the serotonin transporter (SERT) in astrocytes. Neurochem Res 38:694–704

    Article  CAS  PubMed  Google Scholar 

  • Masuda T, Nakagawa S, Boku S et al (2012) Noradrenaline increases neural precursor cells derived from adult rat dentate gyrus through beta2 receptor. Prog Neuro-Psychopharmacol Biol Psychiatry 36:44–51

    Article  CAS  Google Scholar 

  • Matsui TK, Mori E (2018) Microglia support neural stem cell maintenance and growth. Biochem Biophys Res Commun 503:1880–1884

    Article  CAS  PubMed  Google Scholar 

  • Matsui T, Nakata T, Kobayashi Y (2016) Localization of organic cation transporter 2 (OCT2) in monoaminergic and cholinergic axon terminals of the mouse brain. Neurosci Lett 633:118–124

    Article  CAS  PubMed  Google Scholar 

  • Matthaeus F, Schloss P, Lau T (2015) Differential uptake mechanisms of fluorescent substrates into stem-cell-derived serotonergic neurons. ACS Chem Nerosci 6:1906–1912

    Article  CAS  Google Scholar 

  • Ming G-l, Song H (2011) Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 70:687–702

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morris ME, Rodriguez-Cruz V, Felmlee MA (2017) SLC and ABC transporters: expression, localization, and species differences at the blood-brain and the blood-cerebrospinal fluid barriers. AAPS J 19:1317–1331

    Article  PubMed  Google Scholar 

  • Molina-Hernndez A, Velasco I (2008) Histamine induces neural stem cell proliferation and neuronal differentiation by activation of distinct histamine receptors. J Neurochem 106:706–717

    Article  Google Scholar 

  • Mosher KI, Andres RH, Fukuhara T et al (2012) Neural progenitor cells regulate microglia functions and activity. Nat Neurosci 15:1485–1487

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Naganuma F, Yoshikawa T, Nakamura T et al (2014) Predominant role of plasma membrane monoamine transporters in monoamine transport in 1321N1, a human astrocytoma-derived cell line. J Neurochem 129:591–601

    Article  CAS  PubMed  Google Scholar 

  • Nakamichi N, Taguchi T, Hosotani H et al (2012) Functional expression of carnitine/organic cation transporter OCTN1 in mouse brain neurons: possible involvement in neuronal differentiation. Neurochem Int 61:1121–1132

    Article  CAS  PubMed  Google Scholar 

  • Nakamichi N, Nakayama K, Ishimoto T et al (2016) Food-derived hydrophilic antioxidant ergothioneine is distributed to the brain and exerts antidepressant effect in mice. Brain Behav 6:e00477

    Article  PubMed  PubMed Central  Google Scholar 

  • Nakamichi N, Nakao S, Nishiyama M et al (2020) Oral administration of the food derived hydrophilic antioxidant ergothioneine enhances object recognition memory in mice. Curr Mol Pharmacol 14:220–233

    Google Scholar 

  • Nakano C, Takashima S, Takeshita K (1989) Carnitine concentration during the development of human tissues. Early Hum Dev 19:21–27

    Article  CAS  PubMed  Google Scholar 

  • Nakata T, Matsui T, Kobayashi K et al (2013) Organic cation transporter 2 (SLC22A2), a low-affinity and high-capacity choline transporter, is preferentially enriched on synaptic vesicles in cholinergic neurons. Neuroscience 252:212–221

    Article  CAS  PubMed  Google Scholar 

  • Ng TP, Feng L, Yap KB et al (2014) Long-term metformin usage and cognitive function among older adults with diabetes. J Alzheimers Dis 41:61–68

    Article  CAS  PubMed  Google Scholar 

  • O’Donovan SM, Sullivan C, Koene R et al (2018) Cell-subtype-specific changes in adenosine pathways in schizophrenia. Neuropsychopharmacology 43:1667–1674

    Article  PubMed  PubMed Central  Google Scholar 

  • Ohashi R, Tamai I, Yabuuchi H et al (1999) Na+-dependent carnitine transport by organic cation transporter (OCTN2): its pharmacological and toxicological relevance. J Pharmacol Exp Ther 291:778–784

    CAS  PubMed  Google Scholar 

  • Osman AM, Rodhe J, Shen X et al (2019) The secretome of microglia regulate neural stem cell function. Neuroscience 405:92–102

    Article  CAS  PubMed  Google Scholar 

  • Pajarillo E, Rizor A, Lee J et al (2019) The role of astrocytic glutamate transporters GLT-1 and GLAST in neurological disorders: potential targets for neurotherapeutics. Neuropharmacology 161:107559

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pardal R, López Barneo J (2016) Mature neurons modulate neurogenesis through chemical signals acting on neural stem cells. Dev Growth Differ 58:456–462

    Article  PubMed  Google Scholar 

  • Park SY, Kang MJ, Han JS (2018) Interleukin-1 beta promotes neuronal differentiation through the Wnt5a/RhoA/JNK pathway in cortical neural precursor cells. Mol Brain 11:39

    Article  PubMed  PubMed Central  Google Scholar 

  • Perera TD, Park S, Nemirovskaya Y (2008) Cognitive role of neurogenesis in depression and antidepressant treatment. Neuroscientist 14:326–338

    Article  PubMed  Google Scholar 

  • Perez-Villalba A, Sirerol-Piquer MS, Belenguer G et al (2018) Synaptic regulator α-synuclein in dopaminergic fibers is essentially required for the maintenance of subependymal neural stem cells. J Neurosci 38:814–825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pons-Espinal M, Gasperini C, Marzi MJ et al (2019) MiR-135a-5p is critical for exercise-induced adult neurogenesis. Stem Cell Rep 12:1298–1312

    Article  CAS  Google Scholar 

  • Ren-Patterson RF, Kim D, Zheng X et al (2005) Serotonergic-like progenitor cells propagated from neural stem cells in vitro: survival with SERT protein expression following implantation into brains of mice lacking SERT. FASEB J 19:1537–1539

    Article  CAS  PubMed  Google Scholar 

  • Sanchez JF, Crooks DR, Lee CT et al (2006) GABAergic lineage differentiation of AF5 neural progenitor cells in vitro. Cell Tissue Res 324:1–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sánchez-Mendoza EH, Bellver-Landete V, Arce C et al (2017) Vesicular glutamate transporters play a role in neuronal differentiation of cultured SVZderived neural precursor cells. PLoS One 12:e0177069

    Article  PubMed  PubMed Central  Google Scholar 

  • Saraiva C, Barata-Antunes S, Santos T et al (2019) Histamine modulates hippocampal inflammation and neurogenesis in adult mice. Sci Rep 9:8384

    Article  PubMed  PubMed Central  Google Scholar 

  • Schmitt A, Mössner R, Gossmann A et al (2003) Organic cation transporter capable of transporting serotonin is up-regulated in serotonin transporter-deficient mice. J Neurosci Res 71:701–709

    Article  CAS  PubMed  Google Scholar 

  • Schmitt A, Benninghoff J, Moessner R et al (2007) Adult neurogenesis in serotonin transporter deficient mice. J Neural Transm 114:1107–1119

    Article  CAS  PubMed  Google Scholar 

  • Singh S, Mishra A, Mishra SK, Shukla S (2017) ALCAR promote adult hippocampal neurogenesis by regulating cell-survival and cell death-related signals in rat model of Parkinson’s disease like-phenotypes. Neurochem Int 108:388–396

    Article  CAS  PubMed  Google Scholar 

  • Snyder JS, Soumier A, Brewer M et al (2011) Adult hippocampal neurogenesis buffers stress responses and depressive behavior. Nature 476:458–461

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song J, Zhong C, Bonaguidi MA et al (2012) Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision. Nature 489:150–154

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song TY, Lin HC, Chen CL et al (2014) Ergothioneine and melatonin attenuate oxidative stress and protect against learning and memory deficits in C57BL/6J mice treated with D-galactose. Free Radic Res 48:1049–1060

    Article  CAS  PubMed  Google Scholar 

  • Stankiewicz AJ, McGowan EM, Yu L, Zhdanova IV (2017) Impaired sleep, circadian rhythms and neurogenesis in diet-induced premature aging. Int J Mol Sci 18:2243

    Article  PubMed Central  Google Scholar 

  • Syal C, Kosaraju J, Hamilton L et al (2020) Dysregulated expression of monoacylglycerol lipase is a marker for anti-diabetic drug metformin-targeted therapy to correct impaired neurogenesis and spatial memory in Alzheimer’s disease. Theranostics 10:6337–6360

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tamai I, Ohashi R, Nezu JI et al (1998) Molecular and functional identification of sodium ion-dependent, high affinity human carnitine transporter OCTN2. J Biol Chem 273:20378–20382

    Article  CAS  PubMed  Google Scholar 

  • Trujillo-Gonzalez I, Wang Y, Friday WB et al (2019) MicroRNA-129-5p is regulated by choline availability and controls EGF receptor synthesis and neurogenesis in the cerebral cortex. FASEB J 33:3601–3612

    Article  CAS  PubMed  Google Scholar 

  • Tuszynski MH, Yang JH, Barba D et al (2015) Nerve growth factor gene therapy activation of neuronal responses in Alzheimer disease. JAMA Neurol 72:1139–1147

    Article  PubMed  PubMed Central  Google Scholar 

  • Urban T, Brown C, Castro R et al (2008) Effects of genetic variation in the novel organic cation transporter, OCTN1, on the renal clearance of gabapentin. Clin Pharmacol Ther 83:416–421

    Article  CAS  PubMed  Google Scholar 

  • Valente MM, Bortolotto V, Cuccurazzu B et al (2012) α2δ ligands act as positive modulators of adult hippocampal neurogenesis and prevent depression-like behavior induced by chronic restraint stress. Mol Pharmacol 82:271–280

    Article  CAS  PubMed  Google Scholar 

  • Veena J, Rao BSS, Srikumar BN (2011) Regulation of adult neurogenesis in the hippocampus by stress, acetylcholine and dopamine. J Nat Sci Biol Med 2:26–37

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vialou V, Balasse L, Callebert J et al (2008) Altered aminergic neurotransmission in the brain of organic cation transporter 3-deficient mice. J Neurochem 106:1471–1482

    CAS  PubMed  Google Scholar 

  • Wang J, Gallagher D, Devito LM et al (2012) Metformin activates an atypical PKC-CBP pathway to promote neurogenesis and enhance spatial memory formation. Cell Stem Cell 11:23–35

    Article  CAS  PubMed  Google Scholar 

  • Warner-Schmidt JL, Duman RS (2006) Hippocampal neurogenesis: opposing effects of stress and antidepressant treatment. Hippocampus 16:239–249

    Article  CAS  PubMed  Google Scholar 

  • Watanabe N, Matsumoto S, Suzuki M et al (2020) Effect of ergothioneine on the cognitive function improvement in healthy volunteers and mild cognitive impairment subjects–A randomized, double-blind, parallel-group comparison study. Jpn Pharmacol Ther 48:685–697

    CAS  Google Scholar 

  • Wicki-Stordeur XE, Sanchez-Arias XC, Dhaliwal J et al (2016) Pannexin 1 differentially affects neural precursor cell maintenance in the ventricular zone and Peri-infarct cortex. J Neurosci 36:1203–1210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yamada J, Jinno S (2019) Potential link between antidepressant-like effects of ketamine and promotion of adult neurogenesis in the ventral hippocampus of mice. Neuropharmacology 158:107710

    Article  CAS  PubMed  Google Scholar 

  • Yang NC, Lin HC, Wu JH et al (2012) Ergothioneine protects against neuronal injury induced by β-amyloid in mice. Food Chem Toxicol 50:3902–3911

    Article  CAS  PubMed  Google Scholar 

  • Yanpallewar SU, Fernandes K, Marathe SV et al (2010) α2-adrenoceptor blockade accelerates the neurogenic, neurotrophic, and behavioral effects of chronic antidepressant treatment. J Neurosci 30:1096–1109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • You G, Morris ME (2014) Drug transporters: molecular characterization and role in drug disposition, 2nd edn. Wiley, Hoboken

    Google Scholar 

  • Zhang CL, Zou Y, He W et al (2008) A role for adult TLX-positive neural stem cells in learning and behaviour. Nature 451:1004–1007

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Faculty of Pharmacy, Kanazawa University, Kanazawa, Japan

    Takahiro Ishimoto & Yukio Kato

Authors
  1. Takahiro Ishimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yukio Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yukio Kato .

Editor information

Editors and Affiliations

  1. Departments of Cellular and Integrative Physiology, and Pharmacology, University of Texas Health Science Center, San Antonio, TX, USA

    Lynette C. Daws

Rights and permissions

Reprints and permissions

Copyright information

© 2021 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ishimoto, T., Kato, Y. (2021). Regulation of Neurogenesis by Organic Cation Transporters: Potential Therapeutic Implications. In: Daws, L.C. (eds) Organic Cation Transporters in the Central Nervous System. Handbook of Experimental Pharmacology, vol 266. Springer, Cham. https://doi.org/10.1007/164_2021_445

Download citation

Publish with us

Policies and ethics

Search

Navigation