KYNA/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer’s Disease
Abstract
:1. Introduction
2. Materials and Methods
2.1. Ethics Statement
2.2. Animal Maintenance
2.3. Tissue Preparation
2.4. Cerebroventricular Microinjection
2.5. In Situ Hybridization and Immunohistochemistry
2.6. Quantitative Real-Time PCR
2.7. Single Cell Sequencing and Analyses
2.8. Human Bulk RNA-Sequencing
2.9. AD Transcriptome-Wide Association Studies (TWAS) and Meta-Analysis
2.10. Imaging and Quantifications
2.11. Statistical Analyses
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- De Strooper, B.; Karran, E. The Cellular Phase of Alzheimer’s Disease. Cell 2016, 164, 603–615. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Heneka, M.T.; Carson, M.J.; Khoury, J.E.; Landreth, G.E.; Brosseron, F.; Feinstein, D.L.; Jacobs, A.H.; Wyss-Coray, T.; Vitorica, J.; Ransohoff, R.M.; et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015, 14, 388–405. [Google Scholar] [CrossRef][Green Version]
- Selkoe, D.J. Folding proteins in fatal ways. Nature 2003, 426, 900–904. [Google Scholar] [CrossRef] [PubMed]
- Selkoe, D.J. Alzheimer’s disease is a synaptic failure. Science 2002, 298, 789–791. [Google Scholar] [CrossRef][Green Version]
- Selkoe, D.J. Alzheimer’s disease: Genes, proteins, and therapy. Physiol. Rev. 2001, 81, 741–766. [Google Scholar] [CrossRef]
- Mayeux, R.; Stern, Y. Epidemiology of Alzheimer disease. Cold Spring Harb. Perspect. Med. 2012, 2, 111–128. [Google Scholar] [CrossRef][Green Version]
- Arendt, T. Synaptic degeneration in Alzheimer’s disease. Acta Neuropathol. 2009, 118, 167–179. [Google Scholar] [CrossRef]
- Beyreuther, K.; Masters, C.L. Alzheimer’s disease. The ins and outs of amyloid-beta. Nature 1997, 389, 677–678. [Google Scholar] [CrossRef]
- Blennow, K.; de Leon, M.J.; Zetterberg, H. Alzheimer’s disease. Lancet 2006, 368, 387–403. [Google Scholar] [CrossRef]
- Hardy, J.; Selkoe, D.J. The amyloid hypothesis of Alzheimer’s disease: Progress and problems on the road to therapeutics. Science 2002, 297, 353–356. [Google Scholar] [CrossRef][Green Version]
- Mathys, H.; Adaikkan, C.; Gao, F.; Young, J.Z.; Manet, E.; Hemberg, M.; De Jager, P.L.; Ransohoff, R.M.; Regev, A.; Tsai, L.-H. Temporal Tracking of Microglia Activation in Neurodegeneration at Single-Cell Resolution. Cell Rep. 2017, 21, 366–380. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Olah, M.; Menon, V.; Habib, N.; Taga, M.F.; Ma, Y.; Yung, C.J.; Cimpean, M.; Khairallah, A.; Coronas-Samano, G.; Sankowski, R.; et al. Single cell RNA sequencing of human microglia uncovers a subset associated with Alzheimer’s disease. Nat. Commun. 2020, 11, 1–18. [Google Scholar] [CrossRef] [PubMed]
- Heppner, F.L.; Ransohoff, R.M.; Becher, B. Immune attack: The role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 2015, 16, 358–372. [Google Scholar] [CrossRef] [PubMed]
- Jay, T.; Miller, C.M.; Cheng-Hathaway, P.; Graham, L.C.; BeMiller, S.; Broihier, M.L.; Xu, G.; Margevicius, D.; Karlo, J.C.; Sousa, G.; et al. TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models. J. Exp. Med. 2015, 212, 287–295. [Google Scholar] [CrossRef]
- Andrews, S.J.; Fulton-Howard, B.; O’Reilly, P.; Marcora, E.; Goate, A.M. Causal Associations Between Modifiable Risk Factors and the Alzheimer’s Phenome. Ann. Neurol. 2021, 89, 54–65. [Google Scholar] [CrossRef]
- Ji, Y.; Permanne, B.; Sigurdsson, E.M.; Holtzman, D.M.; Wisniewski, T. Amyloid beta40/42 clearance across the blood-brain barrier following intra-ventricular injections in wild-type, apoE knock-out and human apoE3 or E4 expressing transgenic mice. J. Alzheimers Dis. 2001, 3, 23–30. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Moreno-Jiménez, E.P.; Flor-García, M.; Terreros-Roncal, J.; Rábano, A.; Cafini, F.; Pallas-Bazarra, N.; Ávila, J.; Llorens-Martín, M. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat. Med. 2019, 25, 554–560. [Google Scholar] [CrossRef]
- Choi, S.H.; Tanzi, R.E. Is Alzheimer’s Disease a Neurogenesis Disorder? Cell Stem Cell 2019, 25, 7–8. [Google Scholar] [CrossRef]
- Kizil, C.; Bhattarai, P. Is Alzheimer’s Also a Stem Cell Disease?—The Zebrafish Perspective. Front Cell Dev. Biol. 2018, 6, 159. [Google Scholar] [CrossRef][Green Version]
- Kizil, C. Mechanisms of Pathology-Induced Neural Stem Cell Plasticity and Neural Regeneration in Adult Zebrafish Brain. Curr. Pathobiol. Rep. 2018, 6, 71–77. [Google Scholar] [CrossRef][Green Version]
- Cosacak, M.I.; Papadimitriou, C.; Kizil, C. Regeneration, Plasticity, and Induced Molecular Programs in Adult Zebrafish Brain. BioMed Res. Int. 2015, 2015, 1–10. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Tincer, G.; Mashkaryan, V.; Bhattarai, P.; Kizil, C. Neural stem/progenitor cells in Alzheimer’s disease. Yale J. Boil. Med. 2016, 89, 23–35. [Google Scholar]
- Mashkaryan, V.; Siddiqui, T.; Popova, S.; Cosacak, M.I.; Bhattarai, P.; Brandt, K.; Govindarajan, N.; Petzold, A.; Reinhardt, S.; Dahl, A.; et al. Type 1 Interleukin-4 signaling obliterates mouse astroglia in vivo but not in vitro. Front. Cell Dev. Biol. 2020, 8, 114. [Google Scholar] [CrossRef][Green Version]
- Choi, S.H.; Bylykbashi, E.; Chatila, Z.K.; Lee, S.W.; Pulli, B.; Clemenson, G.D.; Kim, E.; Rompala, A.; Oram, M.K.; Asselin, C.; et al. Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model. Science 2018, 361, eaan8821. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Papadimitriou, C.; Celikkaya, H.; Cosacak, M.I.; Mashkaryan, V.; Bray, L.; Bhattarai, P.; Brandt, K.; Hollak, H.; Chen, X.; He, S.; et al. 3D Culture Method for Alzheimer’s Disease Modeling Reveals Interleukin-4 Rescues Abeta42-Induced Loss of Human Neural Stem Cell Plasticity. Dev. Cell 2018, 46, 85–101. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Bhattarai, P.; Thomas, A.K.; Cosacak, M.I.; Papadimitriou, C.; Mashkaryan, V.; Froc, C.; Reinhardt, S.; Kurth, T.; Dahl, A.; Zhang, Y.; et al. IL4/STAT6 signaling activates neural stem cell proliferation and neurogenesis upon Amyloid-β42 aggregation in adult zebrafish brain. Cell Rep. 2016, 17, 941–948. [Google Scholar] [CrossRef][Green Version]
- Martinez-Canabal, A. Reconsidering hippocampal neurogenesis in Alzheimer’s disease. Front. Neurosci. 2014, 8, 2013–2015. [Google Scholar] [CrossRef][Green Version]
- Bhattarai, P.; Thomas, A.K.; Cosacak, M.I.; Papadimitriou, C.; Mashkaryan, V.; Zhang, Y.; Kizil, C. Modeling Amyloid-β42 Toxicity and Neurodegeneration in Adult Zebrafish Brain. J. Vis. Exp. 2017, 128, e56014. [Google Scholar]
- Bhattarai, P.; Thomas, A.K.; Zhang, Y.; Kizil, C. The effects of aging on Amyloid-β42-induced neurodegeneration and regeneration in adult zebrafish brain. Neurogenesis 2017, 4, e1322666. [Google Scholar] [CrossRef]
- Bhattarai, P.; Cosacak, M.I.; Mashkaryan, V.; Demir, S.; Popova, S.D.; Govindarajan, N.; Brandt, K.; Zhang, Y.; Chang, W.; Ampatzis, K.; et al. Neuron-glia interaction through Serotonin-BDNF-NGFR axis enables regenerative neurogenesis in Alzheimer’s model of adult zebrafish brain. PLoS Biol. 2020, 18, e3000585. [Google Scholar] [CrossRef][Green Version]
- Aleström, P.; D’Angelo, L.; Midtlyng, P.J.; Schorderet, D.F.; Schulte-Merker, S.; Sohm, F.; Warner, S. Zebrafish: Housing and husbandry recommendations. Lab. Anim. 2019, 54, 213–224. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Kizil, C.; Iltzsche, A.; Thomas, A.K.; Bhattarai, P.; Zhang, Y.; Brand, M. Efficient cargo delivery using a short cell-penetrating peptide in vertebrate brains. PLoS ONE 2015, 10, e0124073. [Google Scholar] [CrossRef] [PubMed]
- Kizil, C.; Brand, M. Cerebroventricular microinjection (CVMI) into adult zebrafish brain is an efficient misexpression method for forebrain ventricular cells. PLoS ONE 2011, 6, e27395. [Google Scholar] [CrossRef][Green Version]
- Kizil, C.; Kyritsis, N.; Dudczig, S.; Kroehne, V.; Freudenreich, D.; Kaslin, J.; Brand, M. Regenerative neurogenesis from neural progenitor cells requires injury-induced expression of Gata3. Dev. Cell 2012, 23, 1230–1237. [Google Scholar] [CrossRef][Green Version]
- Cosacak, M.I.; Bhattarai, P.; Reinhardt, S.; Petzold, A.; Dahl, A.; Zhang, Y.; Kizil, C. Single-Cell Transcriptomics Analyses of Neural Stem Cell Heterogeneity and Contextual Plasticity in a Zebrafish Brain Model of Amyloid Toxicity. Cell Rep. 2019, 27, 1307–1318. [Google Scholar] [CrossRef][Green Version]
- Felsky, D.; Sariya, S.; Santa-Maria, I.; French, L.; Schneider, J.A.; Bennett, D.A.; Mayeux, R.; De Jager, P.L.; Tosto, G. The Caribbean-Hispanic Alzheimer’s Brain Transcriptome Reveals Ancestry-Specific Disease Mechanisms. bioRxiv 2020. [Google Scholar] [CrossRef]
- De Jager, P.L.; Ma, Y.; McCabe, C.; Xu, J.; Vardarajan, B.N.; Felsky, D.; Klein, H.-U.; White, C.C.; Peters, M.A.; Lodgson, B.; et al. A multi-omic atlas of the human frontal cortex for aging and Alzheimer’s disease research. Sci. Data 2018, 5, 180142. [Google Scholar] [CrossRef] [PubMed]
- Bennett, D.A.; Buchman, A.S.; Boyle, P.A.; Barnes, L.L.; Wilson, R.S.; Schneider, J.A. Religious Orders Study and Rush Memory and Aging Project. J. Alzheimers Dis. 2018, 64, S161–S189. [Google Scholar] [CrossRef]
- Allen, M.; Carrasquillo, M.M.; Funk, C.; Heavner, B.; Zou, F.; Younkin, C.S.; Burgess, J.D.; Chai, H.-S.; Crook, J.; Eddy, J.A.; et al. Human whole genome genotype and transcriptome data for Alzheimer’s and other neurodegenerative diseases. Sci. Data 2016, 3, 160089. [Google Scholar] [CrossRef]
- Robinson, M.D.; McCarthy, D.J.; Smyth, G.K. edgeR: A Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010, 26, 139–140. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Law, C.W.; Chen, Y.; Shi, W.; Smyth, G.K. voom: Precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol. 2014, 15, R29. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Ritchie, M.E.; Phipson, B.; Wu, D.; Hu, Y.; Law, C.W.; Shi, W.; Smyth, G.K. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015, 43, e47. [Google Scholar] [CrossRef] [PubMed]
- Sariya, S.; Felsky, D.; Reyes-Dumeyer, D.; Lali, R.; Lantigua, R.A.; Vardarajan, B.; Jiménez-Velázquez, I.Z.; Haines, J.L.; Shellenberg, G.D.; Pericak-Vance, M.A.; et al. Polygenic risk score for Alzheimer’s Disease in Caribbean Hispanics. Ann. Neurol. 2021, 90, 366–376. [Google Scholar] [CrossRef] [PubMed]
- Tosto, G.; Vardarajan, B.; Sariya, S.; Brickman, A.M.; Andrews, H.; Manly, J.J.; Schupf, N.; Reyes-Dumeyer, D.; Lantigua, R.; Bennett, D.A.; et al. Association of Variants in PINX1 and TREM2 With Late-Onset Alzheimer Disease. JAMA Neurol. 2019, 76, 942–948. [Google Scholar] [CrossRef]
- Wirthgen, E.; Hoeflich, A.; Rebl, A.; Günther, J. Kynurenic Acid: The Janus-Faced Role of an Immunomodulatory Tryptophan Metabolite and Its Link to Pathological Conditions. Front. Immunol. 2018, 8, 1957. [Google Scholar] [CrossRef][Green Version]
- Wang, Q.; Matsumoto, Y.; Shindo, T.; Miyake, K.; Shindo, A.; Kawanishi, M.; Kawai, N.; Tamiya, T.; Nagao, S. Neural stem cells transplantation in cortex in a mouse model of Alzheimer’s disease. J. Med. Investig. JMI 2006, 53, 61–69. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Oxenkrug, G.; Cornicelli, J.; Van Der Hart, M.; Roeser, J.; Summergrad, P. Kynurenic acid, an aryl hydrocarbon receptor ligand, is elevated in serum of Zucker fatty rats. Integr. Mol. Med. 2016, 3, 761–763. [Google Scholar]
- Cosacak, M.I.; Bhattarai, P.; Kizil, C. Alzheimer’s disease, neural stem cells and neurogenesis: Cellular phase at single-cell level. Neural Reg. Res. 2020, 15, 824–827. [Google Scholar]
- Haase, M.; Fitze, G. HSP90AB1: Helping the good and the bad. Gene 2016, 575, 171–186. [Google Scholar] [CrossRef][Green Version]
- Wu, D.; Potluri, N.; Kim, Y.; Rastinejad, F. Structure and dimerization properties of the aryl hydrocarbon receptor PAS-A domain. Mol. Cell Biol. 2013, 33, 4346–4356. [Google Scholar] [CrossRef][Green Version]
- Jurisch-Yaksi, N.; Yaksi, E.; Kizil, C. Radial glia in the zebrafish brain: Functional, structural, and physiological comparison with the mammalian glia. Glia 2020, 68, 2451–2470. [Google Scholar] [CrossRef]
- Wennstrom, M.; Nielsen, H.M.; Orhan, F.; Londos, E.; Minthon, L.; Erhardt, S. Kynurenic Acid levels in cerebrospinal fluid from patients with Alzheimer’s disease or dementia with lewy bodies. Int. J. Tryptophan Res. 2014, 7, 1–7. [Google Scholar] [CrossRef] [PubMed]
- Adams, S.; Teo, C.; McDonald, K.L.; Zinger, A.; Bustamante, S.; Lim, E.; Sundaram, G.; Braidy, N.; Brew, B.; Guillemin, G.J. Involvement of the kynurenine pathway in human glioma pathophysiology. PLoS ONE 2014, 9, e112945. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Walczak, K.; Deneka-Hannemann, S.; Jarosz, B.; Zgrajka, W.; Stoma, F.; Trojanowski, T.; Turski, W.A.; Rzeski, W. Kynurenic acid inhibits proliferation and migration of human glioblastoma T98G cells. Pharmacol. Rep. 2014, 66, 130–136. [Google Scholar] [CrossRef]
- O’Farrell, K.; Fagan, E.; Connor, T.J.; Harkin, A. Inhibition of the kynurenine pathway protects against reactive microglial-associated reductions in the complexity of primary cortical neurons. Eur. J. Pharmacol. 2017, 810, 163–173. [Google Scholar] [CrossRef]
- Turski, W.A.; Małaczewska, J.; Marciniak, S.; Bednarski, J.; Turski, M.P.; Jabłoński, M.; Siwicki, A.K. On the toxicity of kynurenic acid in vivo and in vitro. Pharmacol. Rep. 2014, 66, 1127–1133. [Google Scholar] [CrossRef]
- Ruddick, J.P.; Evans, A.K.; Nutt, D.J.; Lightman, S.; Rook, G.; Lowry, C.A. Tryptophan metabolism in the central nervous system: Medical implications. Expert Rev. Mol. Med. 2006, 8, 1–27. [Google Scholar] [CrossRef]
- Berlinguer-Palmini, R.; Masi, A.; Narducci, R.; Cavone, L.; Maratea, D.; Cozzi, A.; Sili, M.; Moroni, F.; Mannaioni, G. GPR35 activation reduces Ca2+ transients and contributes to the kynurenic acid-dependent reduction of synaptic activity at CA3-CA1 synapses. PLoS ONE 2013, 8, e82180. [Google Scholar] [CrossRef][Green Version]
- Shevtsov, S.P.; Haq, S.; Force, T. Activation of beta-catenin signaling pathways by classical G-protein-coupled receptors: Mechanisms and consequences in cycling and non-cycling cells. Cell Cycle 2006, 5, 2295–2300. [Google Scholar] [CrossRef][Green Version]
- Jenkins, L.; Brea, J.; Smith, N.J.; Hudson, B.D.; Reilly, G.; Bryant, N.J.; Castro, M.; Loza, M.-I.; Milligan, G. Identification of novel species-selective agonists of the G-protein-coupled receptor GPR35 that promote recruitment of beta-arrestin-2 and activate Galpha13. Biochem. J. 2010, 432, 451–459. [Google Scholar] [CrossRef]
- Garcia-Lara, L.; Pérez-Severiano, F.; González-Esquivel, D.; Elizondo, G.; Segovia, J. Absence of aryl hydrocarbon receptors increases endogenous kynurenic acid levels and protects mouse brain against excitotoxic insult and oxidative stress. J. Neurosci. Res. 2015, 93, 1423–1433. [Google Scholar] [CrossRef]
- Kim, I.S.; Hwang, J.-H.; Hirano, M.; Iwata, H.; Kim, E.-Y. In vitro and in silico evaluation of transactivation potencies of avian AHR1 and AHR2 by endogenous ligands: Implications for the physiological role of avian AHR2. Comp. Biochem. Physiol. C Toxicol. Pharm. 2016, 187, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Banerjee, J.; Alkondon, M.; Albuquerque, E.X. Kynurenic acid inhibits glutamatergic transmission to CA1 pyramidal neurons via alpha7 nAChR-dependent and -independent mechanisms. Biochem. Pharm. 2012, 84, 1078–1087. [Google Scholar] [CrossRef]
- Prescott, C.; Weeks, A.M.; Staley, K.J.; Partin, K.M. Kynurenic acid has a dual action on AMPA receptor responses. Neurosci. Lett. 2006, 402, 108–112. [Google Scholar] [CrossRef] [PubMed]
- Weber, M.; Dietrich, D.; Gräsel, I.; Reuter, G.; Seifert, G.; Steinhäuser, C. 6-Hydroxykynurenic acid and kynurenic acid differently antagonise AMPA and NMDA receptors in hippocampal. Neurones J. Neurochem. 2001, 77, 1108–1115. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Di Giaimo, R.; Durovic, T.; Barquin, P.; Kociaj, A.; Lepko, T.; Aschenbroich, S.; Breunig, C.T.; Irmler, M.; Cernilogar, F.; Schotta, G.; et al. The Aryl Hydrocarbon Receptor Pathway Defines the Time Frame for Restorative Neurogenesis. Cell Rep. 2018, 25, 3241–3251. [Google Scholar] [CrossRef] [PubMed][Green Version]
- Gonzalez-Sanchez, M.; Jiménez, J.; Narváez, A.; Antequera, D.; Llamas-Velasco, S.; Martín, A.H.-S.; Arjona, J.A.M.; De Munain, A.L.; Bisa, A.L.; Marco, M.-P.; et al. Kynurenic Acid Levels are Increased in the CSF of Alzheimer’s Disease Patients. Biomolecules 2020, 10, 571. [Google Scholar] [CrossRef][Green Version]
- Hu, L.J.; Li, X.-F.; Hu, J.-Q.; Ni, X.-J.; Lu, H.-Y.; Wang, J.-J.; Huang, X.-N.; Lin, C.-X.; Shang, D.-W.; Wen, Y.-G. A Simple HPLC-MS/MS Method for Determination of Tryptophan, Kynurenine and Kynurenic Acid in Human Serum and its Potential for Monitoring Antidepressant Therapy. J. Anal. Toxicol. 2017, 41, 37–44. [Google Scholar] [CrossRef][Green Version]
- Koshy Cherian, A.; Gritton, H.; Johnson, D.E.; Young, D.; Kozak, R.; Sarter, M. A systemically-available kynurenine aminotransferase II (KAT II) inhibitor restores nicotine-evoked glutamatergic activity in the cortex of rats. Neuropharmacology 2014, 82, 41–48. [Google Scholar] [CrossRef][Green Version]
- Gutierrez-Vazquez, C.; Quintana, F.J. Regulation of the Immune Response by the Aryl Hydrocarbon Receptor. Immunity 2018, 48, 19–33. [Google Scholar] [CrossRef][Green Version]
- Kizil, C.; Kyritsis, N.; Brand, M. Effects of inflammation on stem cells: Together they strive? EMBO Rep. 2015, 16, 416–426. [Google Scholar] [CrossRef] [PubMed]
Gene | Meta Expression | p-Value | DGE Direction | p_FDR |
---|---|---|---|---|
KMO | −0.2009332 | 3.18 × 10−6 | −−− | 6.35 × 10−5 |
AHRR | −0.1683677 | 0.000283 | −−− | 0.0018 |
HSP90AB1 | −0.0585899 | 0.004116 | +−− | 0.01456 |
ARNTL2 | −0.05694 | 0.02121 | −−− | 0.0531 |
AADAT | −0.0449039 | 0.0249 | −−− | 0.06025 |
EPHX1 | 0.0643375 | 0.08271 | +++ | 0.1542 |
AIP | 0.0208076 | 0.2023 | +−+ | 0.3095 |
HSP90AA1 | 0.0092185 | 0.7284 | +++ | 0.8048 |
PTGES3 | −0.0016771 | 0.9305 | +−+ | 0.9536 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Siddiqui, T.; Bhattarai, P.; Popova, S.; Cosacak, M.I.; Sariya, S.; Zhang, Y.; Mayeux, R.; Tosto, G.; Kizil, C. KYNA/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer’s Disease. Cells 2021, 10, 2748. https://doi.org/10.3390/cells10102748
Siddiqui T, Bhattarai P, Popova S, Cosacak MI, Sariya S, Zhang Y, Mayeux R, Tosto G, Kizil C. KYNA/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer’s Disease. Cells. 2021; 10(10):2748. https://doi.org/10.3390/cells10102748
Chicago/Turabian StyleSiddiqui, Tohid, Prabesh Bhattarai, Stanislava Popova, Mehmet Ilyas Cosacak, Sanjeev Sariya, Yixin Zhang, Richard Mayeux, Giuseppe Tosto, and Caghan Kizil. 2021. "KYNA/Ahr Signaling Suppresses Neural Stem Cell Plasticity and Neurogenesis in Adult Zebrafish Model of Alzheimer’s Disease" Cells 10, no. 10: 2748. https://doi.org/10.3390/cells10102748