Enhancement of neurogenesis and cognition through intranasal co-delivery of galanin receptor 2 (GALR2) and neuropeptide Y receptor 1 (NPY1R) agonists: a potential pharmacological strategy for cognitive dysfunctions.
Cognitive enhancement
GALR2 agonists
Intranasal administration
M1145
NPY1R agonists
Neurogenic enhancement
Neuronal differentiation
Neuronal survival
Spatial memory performance
Journal
Behavioral and brain functions : BBF
ISSN: 1744-9081
Titre abrégé: Behav Brain Funct
Pays: England
ID NLM: 101245751
Informations de publication
Date de publication:
28 Mar 2024
28 Mar 2024
Historique:
received:
03
07
2023
accepted:
19
02
2024
medline:
29
3
2024
pubmed:
29
3
2024
entrez:
29
3
2024
Statut:
epublish
Résumé
Spatial memory deficits and reduced neuronal survival contribute to cognitive decline seen in the aging process. Current treatments are limited, emphasizing the need for innovative therapeutic strategies. This research explored the combined effects of intranasally co-administered galanin receptor 2 (GALR2) and neuropeptide Y1 receptor (NPY1R) agonists, recognized for their neural benefits, on spatial memory, neuronal survival, and differentiation in adult rats. After intranasal co-delivery of the GALR2 agonist M1145 and a NPY1R agonist to adult rats, spatial memory was tested with the object-in-place task 3 weeks later. We examined neuronal survival and differentiation by assessing BrdU-IR profiles and doublecortin (DCX) labeled cells, respectively. We also used the GALR2 antagonist M871 to confirm GALR2's crucial role in promoting cell growth. Co-administration improved spatial memory and increased the survival rate of mature neurons. The positive effect of GALR2 in cell proliferation was confirmed by the nullifying effects of its antagonist. The treatment boosted DCX-labeled newborn neurons and altered dendritic morphology, increasing cells with mature dendrites. Our results show that intranasal co-delivery of GALR2 and NPY1R agonists improves spatial memory, boosts neuronal survival, and influences neuronal differentiation in adult rats. The significant role of GALR2 is emphasized, suggesting new potential therapeutic strategies for cognitive decline.
Sections du résumé
BACKGROUND
BACKGROUND
Spatial memory deficits and reduced neuronal survival contribute to cognitive decline seen in the aging process. Current treatments are limited, emphasizing the need for innovative therapeutic strategies. This research explored the combined effects of intranasally co-administered galanin receptor 2 (GALR2) and neuropeptide Y1 receptor (NPY1R) agonists, recognized for their neural benefits, on spatial memory, neuronal survival, and differentiation in adult rats. After intranasal co-delivery of the GALR2 agonist M1145 and a NPY1R agonist to adult rats, spatial memory was tested with the object-in-place task 3 weeks later. We examined neuronal survival and differentiation by assessing BrdU-IR profiles and doublecortin (DCX) labeled cells, respectively. We also used the GALR2 antagonist M871 to confirm GALR2's crucial role in promoting cell growth.
RESULTS
RESULTS
Co-administration improved spatial memory and increased the survival rate of mature neurons. The positive effect of GALR2 in cell proliferation was confirmed by the nullifying effects of its antagonist. The treatment boosted DCX-labeled newborn neurons and altered dendritic morphology, increasing cells with mature dendrites.
CONCLUSIONS
CONCLUSIONS
Our results show that intranasal co-delivery of GALR2 and NPY1R agonists improves spatial memory, boosts neuronal survival, and influences neuronal differentiation in adult rats. The significant role of GALR2 is emphasized, suggesting new potential therapeutic strategies for cognitive decline.
Identifiants
pubmed: 38549164
doi: 10.1186/s12993-024-00230-5
pii: 10.1186/s12993-024-00230-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
6Subventions
Organisme : Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía
ID : UMA18-FEDERJA-100
Organisme : Hjärnfonden
ID : F02018-0286
Organisme : Hjärnfonden
ID : F02019-0296
Organisme : Universidad de Málaga
ID : Funding for open access charge
Organisme : Medicinska Forskningsrådet
ID : 62X-00715-50-3
Organisme : Olle Engkvists Stiftelse
ID : to KF
Informations de copyright
© 2024. The Author(s).
Références
Moreno-Jimenez EP, Flor-Garcia M, Terreros-Roncal J, Rabano A, Cafini F, Pallas-Bazarra N, et al. Adult hippocampal neurogenesis is abundant in neurologically healthy subjects and drops sharply in patients with Alzheimer’s disease. Nat Med. 2019;25(4):554–60.
pubmed: 30911133
doi: 10.1038/s41591-019-0375-9
Terreros-Roncal J, Moreno-Jimenez EP, Flor-Garcia M, Rodriguez-Moreno CB, Trinchero MF, Marquez-Valadez B, et al. Response to comment on “impact of neurodegenerative diseases on human adult hippocampal neurogenesis.” Science. 2022;376(6590):eabo0920.
pubmed: 35420954
pmcid: 7613438
doi: 10.1126/science.abo0920
Kim IB, Park SC. Neural circuitry-neurogenesis coupling model of depression. Int J Mol Sci. 2021;22(5):2468.
pubmed: 33671109
pmcid: 7957816
doi: 10.3390/ijms22052468
Martos D, Tuka B, Tanaka M, Vecsei L, Telegdy G. Memory enhancement with kynurenic acid and its mechanisms in neurotransmission. Biomedicines. 2022;10(4):849.
pubmed: 35453599
pmcid: 9027307
doi: 10.3390/biomedicines10040849
Boldrini M, Fulmore CA, Tartt AN, Simeon LR, Pavlova I, Poposka V, et al. Human Hippocampal neurogenesis persists throughout aging. Cell Stem Cell. 2018;22(4):589–99.
pubmed: 29625071
pmcid: 5957089
doi: 10.1016/j.stem.2018.03.015
Colucci-D’Amato L, Speranza L, Volpicelli F. Neurotrophic Factor BDNF physiological functions and therapeutic potential in depression neurodegeneration and brain cancer. Int J Mol Sci. 2020;21(20):7777.
pubmed: 33096634
pmcid: 7589016
doi: 10.3390/ijms21207777
Serrano-Castro PJ, Garzon-Maldonado FJ, Casado-Naranjo I, Ollero-Ortiz A, Minguez-Castellanos A, Iglesias-Espinosa M, et al. The cognitive and psychiatric subacute impairment in severe Covid-19. Sci Rep. 2022;12(1):3563.
pubmed: 35241761
pmcid: 8894467
doi: 10.1038/s41598-022-07559-9
Kempermann G, Song H, Gage FH. Neurogenesis in the adult hippocampus. Cold Spring Harb Perspect Biol. 2015;7(9): a018812.
pubmed: 26330519
pmcid: 4563705
doi: 10.1101/cshperspect.a018812
Deuel TA, Liu JS, Corbo JC, Yoo SY, Rorke-Adams LB, Walsh CA. Genetic interactions between doublecortin and doublecortin-like kinase in neuronal migration and axon outgrowth. Neuron. 2006;49(1):41–53.
pubmed: 16387638
doi: 10.1016/j.neuron.2005.10.038
Nacher J, Crespo C, McEwen BS. Doublecortin expression in the adult rat telencephalon. Eur J Neurosci. 2001;14(4):629–44.
pubmed: 11556888
doi: 10.1046/j.0953-816x.2001.01683.x
Ribak CE, Korn MJ, Shan Z, Obenaus A. Dendritic growth cones and recurrent basal dendrites are typical features of newly generated dentate granule cells in the adult hippocampus. Brain Res. 2004;1000(1–2):195–9.
pubmed: 15053968
doi: 10.1016/j.brainres.2004.01.011
Canatelli-Mallat M, Chiavellini P, Lehmann M, Goya RG, Morel GR. Age-related loss of recognition memory and its correlation with hippocampal and perirhinal cortex changes in female Sprague Dawley rats. Behav Brain Res. 2022;435: 114026.
pubmed: 35940248
doi: 10.1016/j.bbr.2022.114026
Diaz-Sanchez E, Lopez-Salas A, Mirchandani-Duque M, Alvarez-Contino JE, Sanchez-Perez JA, Fuxe K, et al. Decreased medial prefrontal cortex activity related to impaired novel object preference task performance following GALR2 and Y1R agonists intranasal infusion. Biomed Pharmacother. 2023;161: 114433.
pubmed: 36848750
doi: 10.1016/j.biopha.2023.114433
Brandt MD, Jessberger S, Steiner B, Kronenberg G, Reuter K, Bick-Sander A, et al. Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice. Mol Cell Neurosci. 2003;24(3):603–13.
pubmed: 14664811
doi: 10.1016/S1044-7431(03)00207-0
Steiner B, Kronenberg G, Jessberger S, Brandt MD, Reuter K, Kempermann G. Differential regulation of gliogenesis in the context of adult hippocampal neurogenesis in mice. Glia. 2004;46(1):41–52.
pubmed: 14999812
doi: 10.1002/glia.10337
Kempermann G, Gast D, Kronenberg G, Yamaguchi M, Gage FH. Early determination and long-term persistence of adult-generated new neurons in the hippocampus of mice. Development. 2003;130(2):391–9.
pubmed: 12466205
doi: 10.1242/dev.00203
Rao MS, Shetty AK. Efficacy of doublecortin as a marker to analyse the absolute number and dendritic growth of newly generated neurons in the adult dentate gyrus. Eur J Neurosci. 2004;19(2):234–46.
pubmed: 14725617
doi: 10.1111/j.0953-816X.2003.03123.x
Couillard-Despres S, Winner B, Schaubeck S, Aigner R, Vroemen M, Weidner N, et al. Doublecortin expression levels in adult brain reflect neurogenesis. Eur J Neurosci. 2005;21(1):1–14.
pubmed: 15654838
doi: 10.1111/j.1460-9568.2004.03813.x
Brown JP, Couillard-Despres S, Cooper-Kuhn CM, Winkler J, Aigner L, Kuhn HG. Transient expression of doublecortin during adult neurogenesis. J Comp Neurol. 2003;467(1):1–10.
pubmed: 14574675
doi: 10.1002/cne.10874
Kormos V, Gaszner B. Role of neuropeptides in anxiety, stress, and depression: from animals to humans. Neuropeptides. 2013;47(6):401–19.
pubmed: 24210138
doi: 10.1016/j.npep.2013.10.014
Zaben MJ, Gray WP. Neuropeptides and hippocampal neurogenesis. Neuropeptides. 2013;47(6):431–8.
pubmed: 24215800
doi: 10.1016/j.npep.2013.10.002
Decressac M, Wright B, David B, Tyers P, Jaber M, Barker RA, et al. Exogenous neuropeptide Y promotes in vivo hippocampal neurogenesis. Hippocampus. 2011;21(3):233–8.
pubmed: 20095007
doi: 10.1002/hipo.20765
Howell OW, Silva S, Scharfman HE, Sosunov AA, Zaben M, Shtaya A, et al. Neuropeptide Y is important for basal and seizure-induced precursor cell proliferation in the hippocampus. Neurobiol Dis. 2007;26(1):174–88.
pubmed: 17317195
doi: 10.1016/j.nbd.2006.12.014
Hadad-Ophir O, Albrecht A, Stork O, Richter-Levin G. Amygdala activation and GABAergic gene expression in hippocampal sub-regions at the interplay of stress and spatial learning. Front Behav Neurosci. 2014;8:3.
pubmed: 24478650
pmcid: 3896990
doi: 10.3389/fnbeh.2014.00003
Borbely E, Scheich B, Helyes Z. Neuropeptides in learning and memory. Neuropeptides. 2013;47(6):439–50.
pubmed: 24210137
doi: 10.1016/j.npep.2013.10.012
Martel JC, Alagar R, Robitaille Y, Quirion R. Neuropeptide Y receptor binding sites in human brain Possible alteration in Alzheimer’s disease. Brain Res. 1990. https://doi.org/10.1016/0006-8993(90)90082-M .
doi: 10.1016/0006-8993(90)90082-M
pubmed: 2168782
Nilsson CL, Brinkmalm A, Minthon L, Blennow K, Ekman R. Processing of neuropeptide Y, galanin, and somatostatin in the cerebrospinal fluid of patients with Alzheimer’s disease and frontotemporal dementia. Peptides. 2001;22(12):2105–12.
pubmed: 11786197
doi: 10.1016/S0196-9781(01)00571-X
Gotzsche CR, Woldbye DP. The role of NPY in learning and memory. Neuropeptides. 2016;55:79–89.
pubmed: 26454711
doi: 10.1016/j.npep.2015.09.010
Rana T, Behl T, Sehgal A, Singh S, Sharma N, Abdeen A, et al. Exploring the role of neuropeptides in depression and anxiety. Prog Neuropsychopharmacol Biol Psychiatry. 2022;114: 110478.
pubmed: 34801611
doi: 10.1016/j.pnpbp.2021.110478
Katsetos CD, Del Valle L, Geddes JF, Assimakopoulou M, Legido A, Boyd JC, et al. Aberrant localization of the neuronal class III beta-tubulin in astrocytomas. Arch Pathol Lab Med. 2001;125(5):613–24.
pubmed: 11300931
doi: 10.5858/2001-125-0613-ALOTNC
Abbosh C, Lawkowski A, Zaben M, Gray W. GalR2/3 mediates proliferative and trophic effects of galanin on postnatal hippocampal precursors. J Neurochem. 2011;117(3):425–36.
pubmed: 21281311
doi: 10.1111/j.1471-4159.2011.07204.x
Beck B, Pourie G. Ghrelin, neuropeptide Y, and other feeding-regulatory peptides active in the hippocampus: role in learning and memory. Nutr Rev. 2013;71(8):541–61.
pubmed: 23865799
doi: 10.1111/nure.12045
Li L, Yu L, Kong Q. Exogenous galanin attenuates spatial memory impairment and decreases hippocampal beta-amyloid levels in rat model of Alzheimer’s disease. Int J Neurosci. 2013;123(11):759–65.
pubmed: 23687905
doi: 10.3109/00207454.2013.800976
Narvaez M, Millon C, Borroto-Escuela D, Flores-Burgess A, Santin L, Parrado C, et al. Galanin receptor 2-neuropeptide Y Y1 receptor interactions in the amygdala lead to increased anxiolytic actions. Brain Struct Funct. 2015;220(4):2289–301.
pubmed: 24841617
doi: 10.1007/s00429-014-0788-7
Narvaez M, Borroto-Escuela DO, Millon C, Gago B, Flores-Burgess A, Santin L, et al. Galanin receptor 2-neuropeptide Y Y1 receptor interactions in the dentate gyrus are related with antidepressant-like effects. Brain Struct Funct. 2016;221(8):4129–39.
pubmed: 26666529
doi: 10.1007/s00429-015-1153-1
Narvaez M, Borroto-Escuela DO, Santin L, Millon C, Gago B, Flores-Burgess A, et al. A Novel integrative mechanism in anxiolytic behavior induced by Galanin 2/Neuropeptide Y Y1 receptor interactions on medial paracapsular intercalated amygdala in rats. Front Cell Neurosci. 2018;12:119.
pubmed: 29765307
pmcid: 5938606
doi: 10.3389/fncel.2018.00119
Mirchandani-Duque M, Barbancho MA, Lopez-Salas A, Alvarez-Contino JE, Garcia-Casares N, Fuxe K, et al. Galanin and neuropeptide y interaction enhances proliferation of granule precursor cells and expression of neuroprotective factors in the rat hippocampus with consequent augmented spatial memory. Biomedicines. 2022;10(6):1267.
doi: 10.3390/biomedicines10061297
Borroto-Escuela DO, Pita-Rodriguez M, Fores-Pons R, Barbancho MA, Fuxe K, Narvaez M. Galanin and neuropeptide Y interactions elicit antidepressant activity linked to neuronal precursor cells of the dentate gyrus in the ventral hippocampus. J Cell Physiol. 2021;236(5):3565–78.
pubmed: 33044017
doi: 10.1002/jcp.30092
Borroto-Escuela DO, Fores R, Pita M, Barbancho MA, Zamorano-Gonzalez P, Casares NG, et al. Intranasal delivery of galanin 2 and neuropeptide Y1 agonists enhanced spatial memory performance and neuronal precursor cells proliferation in the dorsal hippocampus in rats. Front Pharmacol. 2022;13: 820210.
pubmed: 35250569
pmcid: 8893223
doi: 10.3389/fphar.2022.820210
Bose M, Farias Quipildor G, Ehrlich ME, Salton SR. Intranasal peptide therapeutics: a promising avenue for overcoming the challenges of traditional CNS drug development. Cells. 2022;11(22):3629.
pubmed: 36429060
pmcid: 9688574
doi: 10.3390/cells11223629
Schmidt-Hieber C, Jonas P, Bischofberger J. Enhanced synaptic plasticity in newly generated granule cells of the adult hippocampus. Nature. 2004;429(6988):184–7.
pubmed: 15107864
doi: 10.1038/nature02553
Bruel-Jungerman E, Laroche S, Rampon C. New neurons in the dentate gyrus are involved in the expression of enhanced long-term memory following environmental enrichment. Eur J Neurosci. 2005;21(2):513–21.
pubmed: 15673450
doi: 10.1111/j.1460-9568.2005.03875.x
Esposito MS, Piatti VC, Laplagne DA, Morgenstern NA, Ferrari CC, Pitossi FJ, et al. Neuronal differentiation in the adult hippocampus recapitulates embryonic development. J Neurosci. 2005;25(44):10074–86.
pubmed: 16267214
pmcid: 6725804
doi: 10.1523/JNEUROSCI.3114-05.2005
Zhao C, Teng EM, Summers RG Jr, Ming GL, Gage FH. Distinct morphological stages of dentate granule neuron maturation in the adult mouse hippocampus. J Neurosci. 2006;26(1):3–11.
pubmed: 16399667
pmcid: 6674324
doi: 10.1523/JNEUROSCI.3648-05.2006
Snyder JS, Choe JS, Clifford MA, Jeurling SI, Hurley P, Brown A, et al. Adult-born hippocampal neurons are more numerous, faster maturing, and more involved in behavior in rats than in mice. J Neurosci. 2009;29(46):14484–95.
pubmed: 19923282
pmcid: 2830901
doi: 10.1523/JNEUROSCI.1768-09.2009
Fuzesi T, Wittmann G, Liposits Z, Lechan RM, Fekete C. Contribution of noradrenergic and adrenergic cell groups of the brainstem and agouti-related protein-synthesizing neurons of the arcuate nucleus to neuropeptide-y innervation of corticotropin-releasing hormone neurons in hypothalamic paraventricular nucleus of the rat. Endocrinology. 2007;148(11):5442–50.
pubmed: 17690163
doi: 10.1210/en.2007-0732
Gelfo F, Tirassa P, De Bartolo P, Croce N, Bernardini S, Caltagirone C, et al. NPY intraperitoneal injections produce antidepressant-like effects and downregulate BDNF in the rat hypothalamus. CNS Neurosci Ther. 2012;18(6):487–92.
pubmed: 22672302
pmcid: 6493532
doi: 10.1111/j.1755-5949.2012.00314.x
Warburton EC, Brown MW. Neural circuitry for rat recognition memory. Behav Brain Res. 2015;285:131–9.
pubmed: 25315129
pmcid: 4383363
doi: 10.1016/j.bbr.2014.09.050
Harrison FE, Hosseini AH, McDonald MP. Endogenous anxiety and stress responses in water maze and Barnes maze spatial memory tasks. Behav Brain Res. 2009;198(1):247–51.
pubmed: 18996418
doi: 10.1016/j.bbr.2008.10.015
Alvarez-Contino JE, Diaz-Sanchez E, Mirchandani-Duque M, Sanchez-Perez JA, Barbancho MA, Lopez-Salas A, et al. GALR2 and Y1R agonists intranasal infusion enhanced adult ventral hippocampal neurogenesis and antidepressant-like effects involving BDNF actions. J Cell Physiol. 2023;4(2):459.
doi: 10.1002/jcp.30944
Ampuero E, Stehberg J, Gonzalez D, Besser N, Ferrero M, Diaz-Veliz G, et al. Repetitive fluoxetine treatment affects long-term memories but not learning. Behav Brain Res. 2013;247:92–100.
pubmed: 23511254
doi: 10.1016/j.bbr.2013.03.011
Barker GR, Warburton EC. Object-in-place associative recognition memory depends on glutamate receptor neurotransmission within two defined hippocampal-cortical circuits: a critical role for AMPA and NMDA receptors in the hippocampus, perirhinal, and prefrontal cortices. Cereb Cortex. 2015;25(2):472–81.
pubmed: 24035904
doi: 10.1093/cercor/bht245
Morales-Medina JC, Juarez I, Venancio-Garcia E, Cabrera SN, Menard C, Yu W, et al. Impaired structural hippocampal plasticity is associated with emotional and memory deficits in the olfactory bulbectomized rat. Neuroscience. 2013;236:233–43.
pubmed: 23357118
doi: 10.1016/j.neuroscience.2013.01.037
Mechawar N, Saghatelyan A, Grailhe R, Scoriels L, Gheusi G, Gabellec MM, et al. Nicotinic receptors regulate the survival of newborn neurons in the adult olfactory bulb. Proc Natl Acad Sci USA. 2004;101(26):9822–6.
pubmed: 15210938
pmcid: 470758
doi: 10.1073/pnas.0403361101
Corvino V, Marchese E, Podda MV, Lattanzi W, Giannetti S, Di Maria V, et al. The neurogenic effects of exogenous neuropeptide y: early molecular events and long-lasting effects in the hippocampus of trimethyltin-treated rats. PLoS ONE. 2014;9(2): e88294.
pubmed: 24516629
pmcid: 3917853
doi: 10.1371/journal.pone.0088294
Cohen H, Zohar J, Kaplan Z, Arnt J. Adjunctive treatment with brexpiprazole and escitalopram reduces behavioral stress responses and increase hypothalamic NPY immunoreactivity in a rat model of PTSD-like symptoms. Eur Neuropsychopharmacol. 2018;28(1):63–74.
pubmed: 29224968
doi: 10.1016/j.euroneuro.2017.11.017
Vega-Rivera NM, Fernandez-Guasti A, Ramirez-Rodriguez G, Estrada-Camarena E. Effect of sub-optimal doses of fluoxetine plus estradiol on antidepressant-like behavior and hippocampal neurogenesis in ovariectomized rats. Psychoneuroendocrinology. 2015;57:113–24.
pubmed: 25917885
doi: 10.1016/j.psyneuen.2015.03.022
Scott GA, Terstege DJ, Roebuck AJ, Gorzo KA, Vu AP, Howland JG, et al. Adult neurogenesis mediates forgetting of multiple types of memory in the rat. Mol Brain. 2021;14(1):97.
pubmed: 34174906
pmcid: 8236170
doi: 10.1186/s13041-021-00808-4
Wadhwa M, Prabhakar A, Ray K, Roy K, Kumari P, Jha PK, et al. Inhibiting the microglia activation improves the spatial memory and adult neurogenesis in rat hippocampus during 48 h of sleep deprivation. J Neuroinflammation. 2017;14(1):222.
pubmed: 29141671
pmcid: 5688670
doi: 10.1186/s12974-017-0998-z
Plumpe T, Ehninger D, Steiner B, Klempin F, Jessberger S, Brandt M, et al. Variability of doublecortin-associated dendrite maturation in adult hippocampal neurogenesis is independent of the regulation of precursor cell proliferation. BMC Neurosci. 2006;7:77.
pubmed: 17105671
pmcid: 1657022
doi: 10.1186/1471-2202-7-77
Ramirez-Rodriguez G, Ortiz-Lopez L, Dominguez-Alonso A, Benitez-King GA, Kempermann G. Chronic treatment with melatonin stimulates dendrite maturation and complexity in adult hippocampal neurogenesis of mice. J Pineal Res. 2011;50(1):29–37.
pubmed: 20880317
doi: 10.1111/j.1600-079X.2010.00802.x
Yagi S, Splinter JEJ, Tai D, Wong S, Wen Y, Galea LAM. Sex differences in maturation and attrition of adult neurogenesis in the hippocampus. ENeuro. 2020. https://doi.org/10.1523/ENEURO.0468-19.2020 .
doi: 10.1523/ENEURO.0468-19.2020
pubmed: 32586842
pmcid: 7369314
van Praag H, Schinder AF, Christie BR, Toni N, Palmer TD, Gage FH. Functional neurogenesis in the adult hippocampus. Nature. 2002;415(6875):1030–4.
pubmed: 11875571
pmcid: 9284568
doi: 10.1038/4151030a
Kim KK, Adelstein RS, Kawamoto S. Identification of neuronal nuclei (NeuN) as Fox-3, a new member of the Fox-1 gene family of splicing factors. J Biol Chem. 2009;284(45):31052–61.
pubmed: 19713214
pmcid: 2781505
doi: 10.1074/jbc.M109.052969
Francis F, Koulakoff A, Boucher D, Chafey P, Schaar B, Vinet MC, et al. Doublecortin is a developmentally regulated, microtubule-associated protein expressed in migrating and differentiating neurons. Neuron. 1999;23(2):247–56.
pubmed: 10399932
doi: 10.1016/S0896-6273(00)80777-1
Lamprecht R, LeDoux J. Structural plasticity and memory. Nat Rev Neurosci. 2004;5(1):45–54.
pubmed: 14708003
doi: 10.1038/nrn1301