The dopamine analogue CA140 alleviates AD pathology, neuroinflammation, and rescues synaptic/cognitive functions by modulating DRD1 signaling or directly binding to Abeta.
Animals
Alzheimer Disease
/ drug therapy
Mice
Mice, Transgenic
Amyloid beta-Peptides
/ metabolism
Neuroinflammatory Diseases
/ drug therapy
Signal Transduction
/ drug effects
Receptors, Dopamine D1
/ metabolism
Synapses
/ drug effects
Cognition
/ drug effects
Dopamine
/ metabolism
Mice, Inbred C57BL
Male
Humans
Aβ
CA140
Dopamine D1 receptor
LTP
Learning and memory
Reactive gliosis
Tau
Journal
Journal of neuroinflammation
ISSN: 1742-2094
Titre abrégé: J Neuroinflammation
Pays: England
ID NLM: 101222974
Informations de publication
Date de publication:
11 Aug 2024
11 Aug 2024
Historique:
received:
10
07
2023
accepted:
17
07
2024
medline:
12
8
2024
pubmed:
12
8
2024
entrez:
11
8
2024
Statut:
epublish
Résumé
We recently reported that the dopamine (DA) analogue CA140 modulates neuroinflammatory responses in lipopolysaccharide-injected wild-type (WT) mice and in 3-month-old 5xFAD mice, a model of Alzheimer's disease (AD). However, the effects of CA140 on Aβ/tau pathology and synaptic/cognitive function and its molecular mechanisms of action are unknown. To investigate the effects of CA140 on cognitive and synaptic function and AD pathology, 3-month-old WT mice or 8-month-old (aged) 5xFAD mice were injected with vehicle (10% DMSO) or CA140 (30 mg/kg, i.p.) daily for 10, 14, or 17 days. Behavioral tests, ELISA, electrophysiology, RNA sequencing, real-time PCR, Golgi staining, immunofluorescence staining, and western blotting were conducted. In aged 5xFAD mice, a model of AD pathology, CA140 treatment significantly reduced Aβ/tau fibrillation, Aβ plaque number, tau hyperphosphorylation, and neuroinflammation by inhibiting NLRP3 activation. In addition, CA140 treatment downregulated the expression of cxcl10, a marker of AD-associated reactive astrocytes (RAs), and c1qa, a marker of the interaction of RAs with disease-associated microglia (DAMs) in 5xFAD mice. CA140 treatment also suppressed the mRNA levels of s100β and cxcl10, markers of AD-associated RAs, in primary astrocytes from 5xFAD mice. In primary microglial cells from 5xFAD mice, CA140 treatment increased the mRNA levels of markers of homeostatic microglia (cx3cr1 and p2ry12) and decreased the mRNA levels of a marker of proliferative region-associated microglia (gpnmb) and a marker of lipid-droplet-accumulating microglia (cln3). Importantly, CA140 treatment rescued scopolamine (SCO)-mediated deficits in long-term memory, dendritic spine number, and LTP impairment. In aged 5xFAD mice, these effects of CA140 treatment on cognitive/synaptic function and AD pathology were regulated by dopamine D1 receptor (DRD1)/Elk1 signaling. In primary hippocampal neurons and WT mice, CA140 treatment promoted long-term memory and dendritic spine formation via effects on DRD1/CaMKIIα and/or ERK signaling. Our results indicate that CA140 improves neuronal/synaptic/cognitive function and ameliorates Aβ/tau pathology and neuroinflammation by modulating DRD1 signaling in primary hippocampal neurons, primary astrocytes/microglia, WT mice, and aged 5xFAD mice.
Sections du résumé
BACKGROUND
BACKGROUND
We recently reported that the dopamine (DA) analogue CA140 modulates neuroinflammatory responses in lipopolysaccharide-injected wild-type (WT) mice and in 3-month-old 5xFAD mice, a model of Alzheimer's disease (AD). However, the effects of CA140 on Aβ/tau pathology and synaptic/cognitive function and its molecular mechanisms of action are unknown.
METHODS
METHODS
To investigate the effects of CA140 on cognitive and synaptic function and AD pathology, 3-month-old WT mice or 8-month-old (aged) 5xFAD mice were injected with vehicle (10% DMSO) or CA140 (30 mg/kg, i.p.) daily for 10, 14, or 17 days. Behavioral tests, ELISA, electrophysiology, RNA sequencing, real-time PCR, Golgi staining, immunofluorescence staining, and western blotting were conducted.
RESULTS
RESULTS
In aged 5xFAD mice, a model of AD pathology, CA140 treatment significantly reduced Aβ/tau fibrillation, Aβ plaque number, tau hyperphosphorylation, and neuroinflammation by inhibiting NLRP3 activation. In addition, CA140 treatment downregulated the expression of cxcl10, a marker of AD-associated reactive astrocytes (RAs), and c1qa, a marker of the interaction of RAs with disease-associated microglia (DAMs) in 5xFAD mice. CA140 treatment also suppressed the mRNA levels of s100β and cxcl10, markers of AD-associated RAs, in primary astrocytes from 5xFAD mice. In primary microglial cells from 5xFAD mice, CA140 treatment increased the mRNA levels of markers of homeostatic microglia (cx3cr1 and p2ry12) and decreased the mRNA levels of a marker of proliferative region-associated microglia (gpnmb) and a marker of lipid-droplet-accumulating microglia (cln3). Importantly, CA140 treatment rescued scopolamine (SCO)-mediated deficits in long-term memory, dendritic spine number, and LTP impairment. In aged 5xFAD mice, these effects of CA140 treatment on cognitive/synaptic function and AD pathology were regulated by dopamine D1 receptor (DRD1)/Elk1 signaling. In primary hippocampal neurons and WT mice, CA140 treatment promoted long-term memory and dendritic spine formation via effects on DRD1/CaMKIIα and/or ERK signaling.
CONCLUSIONS
CONCLUSIONS
Our results indicate that CA140 improves neuronal/synaptic/cognitive function and ameliorates Aβ/tau pathology and neuroinflammation by modulating DRD1 signaling in primary hippocampal neurons, primary astrocytes/microglia, WT mice, and aged 5xFAD mice.
Identifiants
pubmed: 39129007
doi: 10.1186/s12974-024-03180-x
pii: 10.1186/s12974-024-03180-x
doi:
Substances chimiques
Amyloid beta-Peptides
0
Receptors, Dopamine D1
0
Drd1 protein, mouse
0
Dopamine
VTD58H1Z2X
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
200Subventions
Organisme : Korea Brain Research Institute
ID : 23-BR-01-02
Organisme : Korea Brain Research Institute
ID : 21-BR-02-12
Organisme : Korea Brain Research Institute
ID : 24-BR-02-03, 23-BR-02-12, 24-BR-03-07, 24-BR-05-02, 24-BR-03-01, and 24-BR-03-05
Organisme : NRF
ID : RS-2023-00253215
Organisme : National Institute on Aging at the National Institutes of Health
ID : R01AG053577
Organisme : Korea Basic Science Institute
ID : C320000
Organisme : the National Research Foundation of Korea (NRF)
ID : 2022R1A2C1011793
Organisme : the National Research Foundation of Korea (NRF)
ID : 2021R1A4A1031644, 2021M3A9G8022960, 2022M325E8017907
Organisme : the National Research Foundation of Korea (NRF)
ID : 2019R1A2B5B01070108
Informations de copyright
© 2024. The Author(s).
Références
DeTure MA, Dickson DW. The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener. 2019;14(1):32.
pubmed: 31375134
pmcid: 6679484
doi: 10.1186/s13024-019-0333-5
DeKosky ST, Scheff SW. Synapse loss in frontal cortex biopsies in Alzheimer’s disease: correlation with cognitive severity. Ann Neurol. 1990;27(5):457–64.
pubmed: 2360787
doi: 10.1002/ana.410270502
Sobue A, Komine O, Yamanaka K. Neuroinflammation in Alzheimer’s disease: microglial signature and their relevance to disease. Inflamm Regen. 2023;43(1):26.
pubmed: 37165437
pmcid: 10170691
doi: 10.1186/s41232-023-00277-3
Muzio L, Viotti A, Martino G. Microglia in neuroinflammation and neurodegeneration: from understanding to therapy. Front Neurosci. 2021;15: 742065.
pubmed: 34630027
pmcid: 8497816
doi: 10.3389/fnins.2021.742065
Perez-Nievas BG, Serrano-Pozo A. Deciphering the astrocyte reaction in Alzheimer’s disease. Front Aging Neurosci. 2018;10:114.
pubmed: 29922147
pmcid: 5996928
doi: 10.3389/fnagi.2018.00114
Selkoe DJ. Resolving controversies on the path to Alzheimer’s therapeutics. Nat Med. 2011;17(9):1060–5.
pubmed: 21900936
doi: 10.1038/nm.2460
Kramar CP, Chefer VI, Wise RA, Medina JH, Barbano MF. Dopamine in the dorsal hippocampus impairs the late consolidation of cocaine-associated memory. Neuropsychopharmacology. 2014;39(7):1645–53.
pubmed: 24442095
pmcid: 4023137
doi: 10.1038/npp.2014.11
Yagishita S, Hayashi-Takagi A, Ellis-Davies GC, Urakubo H, Ishii S, Kasai H. A critical time window for dopamine actions on the structural plasticity of dendritic spines. Science. 2014;345(6204):1616–20.
pubmed: 25258080
pmcid: 4225776
doi: 10.1126/science.1255514
Rezaei M, Sadeghian A, Roohi N, Shojaei A, Mirnajafi-Zadeh J. Epilepsy and dopaminergic system. Physiol Pharmacol. 2017;21(1):1–14.
Pan X, Kaminga AC, Wen SW, Wu X, Acheampong K, Liu A. Dopamine and dopamine receptors in Alzheimer’s disease: a systematic review and network meta-analysis. Front Aging Neurosci. 2019;11:175.
pubmed: 31354471
pmcid: 6637734
doi: 10.3389/fnagi.2019.00175
Dubovyk V, Manahan-Vaughan D. Gradient of expression of dopamine D2 receptors along the dorso-ventral axis of the hippocampus. Front Synaptic Neurosci. 2019;11:28.
pubmed: 31680927
pmcid: 6803426
doi: 10.3389/fnsyn.2019.00028
Fasano C, Bourque MJ, Lapointe G, Leo D, Thibault D, Haber M, Kortleven C, Desgroseillers L, Murai KK, Trudeau LE. Dopamine facilitates dendritic spine formation by cultured striatal medium spiny neurons through both D1 and D2 dopamine receptors. Neuropharmacology. 2013;67:432–43.
pubmed: 23231809
doi: 10.1016/j.neuropharm.2012.11.030
de Lima MN, Presti-Torres J, Dornelles A, Scalco FS, Roesler R, Garcia VA, Schroder N. Modulatory influence of dopamine receptors on consolidation of object recognition memory. Neurobiol Learn Mem. 2011;95(3):305–10.
pubmed: 21187154
doi: 10.1016/j.nlm.2010.12.007
Lemon N, Manahan-Vaughan D. Dopamine D1/D5 receptors gate the acquisition of novel information through hippocampal long-term potentiation and long-term depression. J Neurosci. 2006;26(29):7723–9.
pubmed: 16855100
pmcid: 6674280
doi: 10.1523/JNEUROSCI.1454-06.2006
Xia QP, Cheng ZY, He L. The modulatory role of dopamine receptors in brain neuroinflammation. Int Immunopharmacol. 2019;76: 105908.
pubmed: 31622861
doi: 10.1016/j.intimp.2019.105908
Pike AF, Longhena F, Faustini G, van Eik JM, Gombert I, Herrebout MAC, Fayed M, Sandre M, Varanita T, Teunissen CE, et al. Dopamine signaling modulates microglial NLRP3 inflammasome activation: implications for Parkinson’s disease. J Neuroinflamm. 2022;19(1):50.
doi: 10.1186/s12974-022-02410-4
Lee JY, Nam JH, Nam Y, Nam HY, Yoon G, Ko E, Kim SB, Bautista MR, Capule CC, Koyanagi T, et al. The small molecule CA140 inhibits the neuroinflammatory response in wild-type mice and a mouse model of AD. J Neuroinflamm. 2018;15(1):286.
doi: 10.1186/s12974-018-1321-3
Na D, Zhang J, Beaulac HJ, Piekna-Przybylska D, Nicklas PR, Kiernan AE, White PM. Increased central auditory gain in 5xFAD Alzheimer’s disease mice as an early biomarker candidate for Alzheimer’s disease diagnosis. Front Neurosci. 2023;17:1106570.
pubmed: 37304021
pmcid: 10250613
doi: 10.3389/fnins.2023.1106570
Abaandou L, Quan D, Shiloach J. Affecting HEK293 cell growth and production performance by modifying the expression of specific genes. Cells. 2021;10(7):1667.
pubmed: 34359846
pmcid: 8304725
doi: 10.3390/cells10071667
Hoe HS, Freeman J, Rebeck GW. Apolipoprotein E decreases tau kinases and phospho-tau levels in primary neurons. Mol Neurodegener. 2006;1:18.
pubmed: 17166269
pmcid: 1713232
doi: 10.1186/1750-1326-1-18
Pak DT, Yang S, Rudolph-Correia S, Kim E, Sheng M. Regulation of dendritic spine morphology by SPAR, a PSD-95-associated RapGAP. Neuron. 2001;31(2):289–303.
pubmed: 11502259
doi: 10.1016/S0896-6273(01)00355-5
van Gijsel-Bonnello M, Baranger K, Benech P, Rivera S, Khrestchatisky M, de Reggi M, Gharib B. Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse model of Alzheimer’s disease: alleviation by pantethine. PLoS ONE. 2017;12(4): e0175369.
pubmed: 28410378
pmcid: 5391924
doi: 10.1371/journal.pone.0175369
Ryu KY, Lee HJ, Woo H, Kang RJ, Han KM, Park H, Lee SM, Lee JY, Jeong YJ, Nam HW, et al. Dasatinib regulates LPS-induced microglial and astrocytic neuroinflammatory responses by inhibiting AKT/STAT3 signaling. J Neuroinflamm. 2019;16(1):190.
doi: 10.1186/s12974-019-1561-x
Ehrlich RS, Shiao AL, Li M, Teppang KL, Jeoung KY, Theodorakis EA, Yang J. Exploring the effect of aliphatic substituents on aryl cyano amides on enhancement of fluorescence upon binding to amyloid-beta aggregates. ACS Chem Neurosci. 2021;12(15):2946–52.
pubmed: 34270227
doi: 10.1021/acschemneuro.1c00334
Capule CC, Brown C, Olsen JS, Dewhurst S, Yang J. Oligovalent amyloid-binding agents reduce SEVI-mediated enhancement of HIV-1 infection. J Am Chem Soc. 2012;134(2):905–8.
pubmed: 22239120
pmcid: 3262105
doi: 10.1021/ja210931b
Roche J, Shen Y, Lee JH, Ying J, Bax A. Monomeric Abeta(1–40) and Abeta(1–42) peptides in solution adopt very similar ramachandran map distributions that closely resemble random coil. Biochemistry. 2016;55(5):762–75.
pubmed: 26780756
doi: 10.1021/acs.biochem.5b01259
Nam Y, Joo B, Lee JY, Han KM, Ryu KY, Koh YH, Kim J, Koo JW, We YM, Hoe HS. ALWPs improve cognitive function and regulate Abeta plaque and tau hyperphosphorylation in a mouse model of Alzheimer’s disease. Front Mol Neurosci. 2019;12:192.
pubmed: 31474828
pmcid: 6707392
doi: 10.3389/fnmol.2019.00192
Lee HJ, Hoe HS. Inhibition of CDK4/6 regulates AD pathology, neuroinflammation and cognitive function through DYRK1A/STAT3 signaling. Pharmacol Res. 2023;190: 106725.
pubmed: 36907286
doi: 10.1016/j.phrs.2023.106725
Lee HJ, Jeon SG, Kim J, Kang RJ, Kim SM, Han KM, Park H, Kim KT, Sung YM, Nam HY, et al. Ibrutinib modulates Abeta/tau pathology, neuroinflammation, and cognitive function in mouse models of Alzheimer’s disease. Aging Cell. 2021;20(3): e13332.
pubmed: 33709472
pmcid: 7963331
doi: 10.1111/acel.13332
Trapnell C, Pachter L, Salzberg SL. TopHat: discovering splice junctions with RNA-Seq. Bioinformatics. 2009;25(9):1105–11.
pubmed: 19289445
pmcid: 2672628
doi: 10.1093/bioinformatics/btp120
Anders S, Pyl PT, Huber W. HTSeq–a Python framework to work with high-throughput sequencing data. Bioinformatics. 2015;31(2):166–9.
pubmed: 25260700
doi: 10.1093/bioinformatics/btu638
Robinson MD, Oshlack A. A scaling normalization method for differential expression analysis of RNA-seq data. Genome Biol. 2010;11(3):R25.
pubmed: 20196867
pmcid: 2864565
doi: 10.1186/gb-2010-11-3-r25
Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 2014;15(12):550.
pubmed: 25516281
pmcid: 4302049
doi: 10.1186/s13059-014-0550-8
Sherman BT, Hao M, Qiu J, Jiao X, Baseler MW, Lane HC, Imamichi T, Chang W. DAVID: a web server for functional enrichment analysis and functional annotation of gene lists (2021 update). Nucleic Acids Res. 2022;50(W1):W216–21.
pubmed: 35325185
pmcid: 9252805
doi: 10.1093/nar/gkac194
Kanehisa M, Furumichi M, Sato Y, Ishiguro-Watanabe M, Tanabe M. KEGG: integrating viruses and cellular organisms. Nucleic Acids Res. 2021;49(D1):D545–51.
pubmed: 33125081
doi: 10.1093/nar/gkaa970
Martens M, Ammar A, Riutta A, Waagmeester A, Slenter DN, Hanspers K, Miller RA, Digles D, Lopes EN, Ehrhart F, et al. WikiPathways: connecting communities. Nucleic Acids Res. 2021;49(D1):D613–21.
pubmed: 33211851
doi: 10.1093/nar/gkaa1024
Cataldi R, Chia S, Pisani K, Ruggeri FS, Xu CK, Sneideris T, Perni M, Sarwat S, Joshi P, Kumita JR, et al. A dopamine metabolite stabilizes neurotoxic amyloid-beta oligomers. Commun Biol. 2021;4(1):19.
pubmed: 33398040
pmcid: 7782527
doi: 10.1038/s42003-020-01490-3
Kinney JW, Bemiller SM, Murtishaw AS, Leisgang AM, Salazar AM, Lamb BT. Inflammation as a central mechanism in Alzheimer’s disease. Alzheimers Dement. 2018;4:575–90.
Bernaus A, Blanco S, Sevilla A. Glia crosstalk in neuroinflammatory diseases. Front Cell Neurosci. 2020;14:209.
pubmed: 32848613
pmcid: 7403442
doi: 10.3389/fncel.2020.00209
Lin W, Li Z, Liang G, Zhou R, Zheng X, Tao R, Huo Q, Su C, Li M, Xu N, et al. TNEA therapy promotes the autophagic degradation of NLRP3 inflammasome in a transgenic mouse model of Alzheimer’s disease via TFEB/TFE3 activation. J Neuroinflamm. 2023;20(1):21.
doi: 10.1186/s12974-023-02698-w
Escartin C, Galea E, Lakatos A, O’Callaghan JP, Petzold GC, Serrano-Pozo A, Steinhauser C, Volterra A, Carmignoto G, Agarwal A, et al. Reactive astrocyte nomenclature, definitions, and future directions. Nat Neurosci. 2021;24(3):312–25.
pubmed: 33589835
pmcid: 8007081
doi: 10.1038/s41593-020-00783-4
Yu W, Li Y, Zhong F, Deng Z, Wu J, Yu W, Lu Y. Disease-associated neurotoxic astrocyte markers in Alzheimer disease based on integrative single-nucleus RNA sequencing. Cell Mol Neurobiol. 2024;44(1):20.
pubmed: 38345650
pmcid: 10861702
doi: 10.1007/s10571-024-01453-w
Jo KW, Lee D, Cha DG, Oh E, Choi YH, Kim S, Park ES, Kim JK, Kim KT. Gossypetin ameliorates 5xFAD spatial learning and memory through enhanced phagocytosis against Abeta. Alzheimers Res Ther. 2022;14(1):158.
pubmed: 36271414
pmcid: 9585741
doi: 10.1186/s13195-022-01096-3
Paolicelli RC, Sierra A, Stevens B, Tremblay ME, Aguzzi A, Ajami B, Amit I, Audinat E, Bechmann I, Bennett M, et al. Microglia states and nomenclature: a field at its crossroads. Neuron. 2022;110(21):3458–83.
pubmed: 36327895
pmcid: 9999291
doi: 10.1016/j.neuron.2022.10.020
Li Q, Cheng Z, Zhou L, Darmanis S, Neff NF, Okamoto J, Gulati G, Bennett ML, Sun LO, Clarke LE, et al. Developmental heterogeneity of microglia and brain myeloid cells revealed by deep single-cell RNA sequencing. Neuron. 2019;101(2):207–23.
pubmed: 30606613
doi: 10.1016/j.neuron.2018.12.006
Lee JS, Kim HG, Lee HW, Han JM, Lee SK, Kim DW, Saravanakumar A, Son CG. Hippocampal memory enhancing activity of pine needle extract against scopolamine-induced amnesia in a mouse model. Sci Rep. 2015;5:9651.
pubmed: 25974329
pmcid: 4431316
doi: 10.1038/srep09651
Lee HJ, Woo H, Lee HE, Jeon H, Ryu KY, Nam JH, Jeon SG, Park H, Lee JS, Han KM, et al. The novel DYRK1A inhibitor KVN93 regulates cognitive function, amyloid-beta pathology, and neuroinflammation. Free Radic Biol Med. 2020;160:575–95.
pubmed: 32896600
doi: 10.1016/j.freeradbiomed.2020.08.030
Dorostkar MM, Zou C, Blazquez-Llorca L, Herms J. Analyzing dendritic spine pathology in Alzheimer’s disease: problems and opportunities. Acta Neuropathol. 2015;130(1):1–19.
pubmed: 26063233
pmcid: 4469300
doi: 10.1007/s00401-015-1449-5
Zhang M, Zhong L, Han X, Xiong G, Xu D, Zhang S, Cheng H, Chiu K, Xu Y. Brain and retinal abnormalities in the 5xFAD mouse model of Alzheimer’s disease at early stages. Front Neurosci. 2021;15: 681831.
pubmed: 34366774
pmcid: 8343228
doi: 10.3389/fnins.2021.681831
Forner S, Kawauchi S, Balderrama-Gutierrez G, Kramar EA, Matheos DP, Phan J, Javonillo DI, Tran KM, Hingco E, da Cunha C, et al. Systematic phenotyping and characterization of the 5xFAD mouse model of Alzheimer’s disease. Sci Data. 2021;8(1):270.
pubmed: 34654824
pmcid: 8519958
doi: 10.1038/s41597-021-01054-y
Jourdain P, Fukunaga K, Muller D. Calcium/calmodulin-dependent protein kinase II contributes to activity-dependent filopodia growth and spine formation. J Neurosci. 2003;23(33):10645–9.
pubmed: 14627649
pmcid: 6740921
doi: 10.1523/JNEUROSCI.23-33-10645.2003
Ohta KI, Suzuki S, Warita K, Kaji T, Kusaka T, Miki T. Prolonged maternal separation attenuates BDNF-ERK signaling correlated with spine formation in the hippocampus during early brain development. J Neurochem. 2017;141(2):179–94.
pubmed: 28178750
doi: 10.1111/jnc.13977
Szatmari EM, Oliveira AF, Sumner EJ, Yasuda R. Centaurin-alpha1-Ras-Elk-1 signaling at mitochondria mediates beta-amyloid-induced synaptic dysfunction. J Neurosci. 2013;33(12):5367–74.
pubmed: 23516302
pmcid: 3866502
doi: 10.1523/JNEUROSCI.2641-12.2013
Jones MR, Urits I, Wolf J, Corrigan D, Colburn L, Peterson E, Williamson A, Viswanath O. Drug-induced peripheral neuropathy: a narrative review. Curr Clin Pharmacol. 2020;15(1):38–48.
pubmed: 30666914
pmcid: 7365998
Arendt T, Gartner U, Seeger G, Barmashenko G, Palm K, Mittmann T, Yan L, Hummeke M, Behrbohm J, Bruckner MK, et al. Neuronal activation of Ras regulates synaptic connectivity. Eur J Neurosci. 2004;19(11):2953–66.
pubmed: 15182302
doi: 10.1111/j.0953-816X.2004.03409.x
Zhu JJ, Qin Y, Zhao M, Van Aelst L, Malinow R. Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell. 2002;110(4):443–55.
pubmed: 12202034
doi: 10.1016/S0092-8674(02)00897-8
Wu L, D’Amico A, Hochrein H, O’Keeffe M, Shortman K, Lucas K. Development of thymic and splenic dendritic cell populations from different hemopoietic precursors. Blood. 2001;98(12):3376–82.
pubmed: 11719377
doi: 10.1182/blood.V98.12.3376
Kempadoo KA, Mosharov EV, Choi SJ, Sulzer D, Kandel ER. Dopamine release from the locus coeruleus to the dorsal hippocampus promotes spatial learning and memory. Proc Natl Acad Sci USA. 2016;113(51):14835–40.
pubmed: 27930324
pmcid: 5187750
doi: 10.1073/pnas.1616515114
Calabresi P, Picconi B, Tozzi A, Di Filippo M. Dopamine-mediated regulation of corticostriatal synaptic plasticity. Trends Neurosci. 2007;30(5):211–9.
pubmed: 17367873
doi: 10.1016/j.tins.2007.03.001
Denenberg VH, Kim DS, Palmiter RD. The role of dopamine in learning, memory, and performance of a water escape task. Behav Brain Res. 2004;148(1–2):73–8.
pubmed: 14684249
doi: 10.1016/S0166-4328(03)00183-9
Jay TM. Dopamine: a potential substrate for synaptic plasticity and memory mechanisms. Prog Neurobiol. 2003;69(6):375–90.
pubmed: 12880632
doi: 10.1016/S0301-0082(03)00085-6
Takeuchi T, Duszkiewicz AJ, Sonneborn A, Spooner PA, Yamasaki M, Watanabe M, Smith CC, Fernandez G, Deisseroth K, Greene RW, et al. Locus coeruleus and dopaminergic consolidation of everyday memory. Nature. 2016;537(7620):357–62.
pubmed: 27602521
pmcid: 5161591
doi: 10.1038/nature19325
Nam E, Derrick JS, Lee S, Kang J, Han J, Lee SJC, Chung SW, Lim MH. regulatory activities of dopamine and its derivatives toward metal-free and metal-induced amyloid-beta aggregation, oxidative stress, and inflammation in Alzheimer’s disease. ACS Chem Neurosci. 2018;9(11):2655–66.
pubmed: 29782798
doi: 10.1021/acschemneuro.8b00122
Li J, Zhu M, Manning-Bog AB, Di Monte DA, Fink AL. Dopamine and L-dopa disaggregate amyloid fibrils: implications for Parkinson’s and Alzheimer’s disease. FASEB J. 2004;18(9):962–4.
pubmed: 15059976
doi: 10.1096/fj.03-0770fje
Cheng ZY, Xia QP, Hu YH, Wang C, He L. Dopamine D1 receptor agonist A-68930 ameliorates Abeta(1–42)-induced cognitive impairment and neuroinflammation in mice. Int Immunopharmacol. 2020;88: 106963.
pubmed: 33182028
doi: 10.1016/j.intimp.2020.106963
Tian J, Guo L, Sui S, Driskill C, Phensy A, Wang Q, Gauba E, Zigman JM, Swerdlow RH, Kroener S, et al. Disrupted hippocampal growth hormone secretagogue receptor 1alpha interaction with dopamine receptor D1 plays a role in Alzheimer’s disease. Sci Transl Med. 2019. https://doi.org/10.1126/scitranslmed.aav6278 .
doi: 10.1126/scitranslmed.aav6278
pubmed: 31748231
pmcid: 6776822
Latz E, Xiao TS, Stutz A. Activation and regulation of the inflammasomes. Nat Rev Immunol. 2013;13(6):397–411.
pubmed: 23702978
doi: 10.1038/nri3452
Yan Y, Jiang W, Liu L, Wang X, Ding C, Tian Z, Zhou R. Dopamine controls systemic inflammation through inhibition of NLRP3 inflammasome. Cell. 2015;160(1–2):62–73.
pubmed: 25594175
doi: 10.1016/j.cell.2014.11.047
Letiembre M, Liu Y, Walter S, Hao W, Pfander T, Wrede A, Schulz-Schaeffer W, Fassbender K. Screening of innate immune receptors in neurodegenerative diseases: a similar pattern. Neurobiol Aging. 2009;30(5):759–68.
pubmed: 17905482
doi: 10.1016/j.neurobiolaging.2007.08.018
Frank S, Copanaki E, Burbach GJ, Muller UC, Deller T. Differential regulation of toll-like receptor mRNAs in amyloid plaque-associated brain tissue of aged APP23 transgenic mice. Neurosci Lett. 2009;453(1):41–4.
pubmed: 19429012
doi: 10.1016/j.neulet.2009.01.075
Walter S, Letiembre M, Liu Y, Heine H, Penke B, Hao W, Bode B, Manietta N, Walter J, Schulz-Schuffer W, et al. Role of the toll-like receptor 4 in neuroinflammation in Alzheimer’s disease. Cell Physiol Biochem. 2007;20(6):947–56.
pubmed: 17982277
doi: 10.1159/000110455
Minoretti P, Gazzaruso C, Vito CD, Emanuele E, Bianchi M, Coen E, Reino M, Geroldi D. Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer’s disease. Neurosci Lett. 2006;391(3):147–9.
pubmed: 16157451
doi: 10.1016/j.neulet.2005.08.047
Jin JJ, Kim HD, Maxwell JA, Li L, Fukuchi K. Toll-like receptor 4-dependent upregulation of cytokines in a transgenic mouse model of Alzheimer’s disease. J Neuroinflamm. 2008;5:23.
doi: 10.1186/1742-2094-5-23
Tahara K, Kim HD, Jin JJ, Maxwell JA, Li L, Fukuchi K. Role of toll-like receptor signalling in Abeta uptake and clearance. Brain. 2006;129(Pt 11):3006–19.
pubmed: 16984903
doi: 10.1093/brain/awl249
Preston GC, Brazell C, Ward C, Broks P, Traub M, Stahl SM. The scopolamine model of dementia: determination of central cholinomimetic effects of physostigmine on cognition and biochemical markers in man. J Psychopharmacol. 1988;2(2):67–79.
pubmed: 22155841
doi: 10.1177/026988118800200202
Stone WS, Croul CE, Gold PE. Attenuation of scopolamine-induced amnesia in mice. Psychopharmacology. 1988;96(3):417–20.
pubmed: 3146778
doi: 10.1007/BF00216073
Ebert U, Kirch W. Scopolamine model of dementia: electroencephalogram findings and cognitive performance. Eur J Clin Invest. 1998;28(11):944–9.
pubmed: 9824440
doi: 10.1046/j.1365-2362.1998.00393.x
Bajo R, Pusil S, Lopez ME, Canuet L, Pereda E, Osipova D, Maestu F, Pekkonen E. Scopolamine effects on functional brain connectivity: a pharmacological model of Alzheimer’s disease. Sci Rep. 2015;5:9748.
pubmed: 26130273
pmcid: 4486953
doi: 10.1038/srep09748
van der Zee EA, Luiten PG. Muscarinic acetylcholine receptors in the hippocampus, neocortex and amygdala: a review of immunocytochemical localization in relation to learning and memory. Prog Neurobiol. 1999;58(5):409–71.
pubmed: 10380240
doi: 10.1016/S0301-0082(98)00092-6
Memo M, Missale C, Trivelli L, Spano PF. Acute scopolamine treatment decreases dopamine metabolism in rat hippocampus and frontal cortex. Eur J Pharmacol. 1988;149(3):367–70.
pubmed: 3409960
doi: 10.1016/0014-2999(88)90670-X
Piri M, Rostampour M, Nasehi M, Zarrindast MR. Blockade of the dorsal hippocampal dopamine D1 receptors inhibits the scopolamine-induced state-dependent learning in rats. Neuroscience. 2013;252:460–7.
pubmed: 23933216
doi: 10.1016/j.neuroscience.2013.08.003
Drever BD, Riedel G, Platt B. The cholinergic system and hippocampal plasticity. Behav Brain Res. 2011;221(2):505–14.
pubmed: 21130117
doi: 10.1016/j.bbr.2010.11.037
Chen J, Nakamura M, Kawamura T, Takahashi T, Nakahara D. Roles of pedunculopontine tegmental cholinergic receptors in brain stimulation reward in the rat. Psychopharmacology. 2006;184(3–4):514–22.
pubmed: 16385418
doi: 10.1007/s00213-005-0252-8
Yuan Xiang P, Janc O, Grochowska KM, Kreutz MR, Reymann KG. Dopamine agonists rescue Abeta-induced LTP impairment by Src-family tyrosine kinases. Neurobiol Aging. 2016;40:98–102.
pubmed: 26973108
doi: 10.1016/j.neurobiolaging.2016.01.008
Kramar CP, Barbano MF, Medina JH. Dopamine D1/D5 receptors in the dorsal hippocampus are required for the acquisition and expression of a single trial cocaine-associated memory. Neurobiol Learn Mem. 2014;116:172–80.
pubmed: 25452086
doi: 10.1016/j.nlm.2014.10.004
Tong L, Balazs R, Thornton PL, Cotman CW. Beta-amyloid peptide at sublethal concentrations downregulates brain-derived neurotrophic factor functions in cultured cortical neurons. J Neurosci. 2004;24(30):6799–809.
pubmed: 15282285
pmcid: 6729714
doi: 10.1523/JNEUROSCI.5463-03.2004
Sharma A, Callahan LM, Sul JY, Kim TK, Barrett L, Kim M, Powers JM, Federoff H, Eberwine J. A neurotoxic phosphoform of Elk-1 associates with inclusions from multiple neurodegenerative diseases. PLoS ONE. 2010;5(2): e9002.
pubmed: 20126313
pmcid: 2814869
doi: 10.1371/journal.pone.0009002
Barrett LE, Sul JY, Takano H, Van Bockstaele EJ, Haydon PG, Eberwine JH. Region-directed phototransfection reveals the functional significance of a dendritically synthesized transcription factor. Nat Methods. 2006;3(6):455–60.
pubmed: 16721379
doi: 10.1038/nmeth885
Zhang YQ, Lin WP, Huang LP, Zhao B, Zhang CC, Yin DM. Dopamine D2 receptor regulates cortical synaptic pruning in rodents. Nat Commun. 2021;12(1):6444.
pubmed: 34750364
pmcid: 8576001
doi: 10.1038/s41467-021-26769-9
Hu YT, Chen XL, Huang SH, Zhu QB, Yu SY, Shen Y, Sluiter A, Verhaagen J, Zhao J, Swaab D, et al. Early growth response-1 regulates acetylcholinesterase and its relation with the course of Alzheimer’s disease. Brain Pathol. 2019;29(4):502–12.
pubmed: 30511454
pmcid: 8028686
doi: 10.1111/bpa.12688
Eu WZ, Chen YJ, Chen WT, Wu KY, Tsai CY, Cheng SJ, Carter RN, Huang GJ. The effect of nerve growth factor on supporting spatial memory depends upon hippocampal cholinergic innervation. Transl Psychiatry. 2021;11(1):162.
pubmed: 33723225
pmcid: 7961060
doi: 10.1038/s41398-021-01280-3
Liu YJ, Liu TT, Jiang LH, Liu Q, Ma ZL, Xia TJ, Gu XP. Identification of hub genes associated with cognition in the hippocampus of Alzheimer’s Disease. Bioengineered. 2021;12(2):9598–609.
pubmed: 34719328
pmcid: 8810106
doi: 10.1080/21655979.2021.1999549
Garofalo L, Ribeiro-da-Silva A, Cuello AC. Nerve growth factor-induced synaptogenesis and hypertrophy of cortical cholinergic terminals. Proc Natl Acad Sci USA. 1992;89(7):2639–43.
pubmed: 1557368
pmcid: 48717
doi: 10.1073/pnas.89.7.2639
Koldamova R, Schug J, Lefterova M, Cronican AA, Fitz NF, Davenport FA, Carter A, Castranio EL, Lefterov I. Genome-wide approaches reveal EGR1-controlled regulatory networks associated with neurodegeneration. Neurobiol Dis. 2014;63:107–14.
pubmed: 24269917
doi: 10.1016/j.nbd.2013.11.005
Kern A, Mavrikaki M, Ullrich C, Albarran-Zeckler R, Brantley AF, Smith RG. Hippocampal dopamine/DRD1 signaling dependent on the ghrelin receptor. Cell. 2015;163(5):1176–90.
pubmed: 26590421
pmcid: 4937825
doi: 10.1016/j.cell.2015.10.062
Barcomb K, Buard I, Coultrap SJ, Kulbe JR, O’Leary H, Benke TA, Bayer KU. Autonomous CaMKII requires further stimulation by Ca2+/calmodulin for enhancing synaptic strength. FASEB J. 2014;28(8):3810–9.
pubmed: 24843070
pmcid: 4101658
doi: 10.1096/fj.14-250407
Pi HJ, Otmakhov N, El Gaamouch F, Lemelin D, De Koninck P, Lisman J. CaMKII control of spine size and synaptic strength: role of phosphorylation states and nonenzymatic action. Proc Natl Acad Sci USA. 2010;107(32):14437–42.
pubmed: 20660727
pmcid: 2922610
doi: 10.1073/pnas.1009268107
Ryu HH, Lee YS. Cell type-specific roles of RAS-MAPK signaling in learning and memory: implications in neurodevelopmental disorders. Neurobiol Learn Mem. 2016;135:13–21.
pubmed: 27296701
doi: 10.1016/j.nlm.2016.06.006
Cornelia Koeberle S, Tanaka S, Kuriu T, Iwasaki H, Koeberle A, Schulz A, Helbing DL, Yamagata Y, Morrison H, Okabe S. Developmental stage-dependent regulation of spine formation by calcium-calmodulin-dependent protein kinase IIalpha and Rap1. Sci Rep. 2017;7(1):13409.
pubmed: 29042611
pmcid: 5645322
doi: 10.1038/s41598-017-13728-y
Wayman GA, Lee YS, Tokumitsu H, Silva AJ, Soderling TR. Calmodulin-kinases: modulators of neuronal development and plasticity. Neuron. 2008;59(6):914–31.
pubmed: 18817731
pmcid: 2664743
doi: 10.1016/j.neuron.2008.08.021
Lee YS, Silva AJ. The molecular and cellular biology of enhanced cognition. Nat Rev Neurosci. 2009;10(2):126–40.
pubmed: 19153576
pmcid: 2664745
doi: 10.1038/nrn2572