Posttreatment with PaPE-1 Protects from Aβ-Induced Neurodegeneration Through Inhibiting the Expression of Alzheimer's Disease-Related Genes and Apoptosis Process That Involves Enhanced DNA Methylation of Specific Genes.

Alzheimer’s disease Amyloid-β Caspases Neuroprotection Non-nuclear estrogen receptor signaling Primary neocortical cell cultures

Journal

Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963

Informations de publication

Date de publication:
08 Dec 2023
Historique:
received: 12 07 2023
accepted: 19 11 2023
medline: 8 12 2023
pubmed: 8 12 2023
entrez: 8 12 2023
Statut: aheadofprint

Résumé

Targeting the non-nuclear estrogen receptor (ER) signaling has been postulated as novel therapeutic strategy for central nervous system pathologies. Recently, we showed that newly designed PaPE-1 (Pathway Preferential Estrogen-1), which selectively activates ER non-nuclear signaling pathways, elicited neuroprotection in a cellular model of Alzheimer's disease (AD) when it was applied at the same time as amyloid-β (Aβ). Since delayed treatment reflects clinical settings better than cotreatment does, current basic study proposes a novel therapeutic approach for AD that relies on a posttreatment with PaPE-1. In this study, mouse neuronal cell cultures treated with preaggregated Aβ

Identifiants

pubmed: 38064105
doi: 10.1007/s12035-023-03819-5
pii: 10.1007/s12035-023-03819-5
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Narodowe Centrum Nauki
ID : 2020/39/B/NZ7/00974
Organisme : Instytut Farmakologii im. Jerzego Maja Polskiej Akademii Nauk
ID : statutory fund

Informations de copyright

© 2023. The Author(s).

Références

Thinakaran G, Koo EH (2008) Amyloid precursor protein trafficking, processing, and function. J Biol Chem 283(44):29615–29619. https://doi.org/10.1074/jbc.R800019200
doi: 10.1074/jbc.R800019200 pubmed: 18650430 pmcid: 2573065
Shimohama S (2000) Apoptosis in Alzheimer’s disease–an update. Apoptosis 5(1):9–16. https://doi.org/10.1023/a:1009625323388
doi: 10.1023/a:1009625323388 pubmed: 11227497
Huang YR, Liu RT (2020) The toxicity and polymorphism of β-amyloid oligomers. Int J Mol Sci 21(12):4477. https://doi.org/10.3390/ijms21124477
doi: 10.3390/ijms21124477 pubmed: 32599696 pmcid: 7352971
Sharma VK, Singh TG, Singh S, Garg N, Dhiman S (2021) Apoptotic pathways and Alzheimer’s disease: probing therapeutic potential. Neurochem Res 46(12):3103–3122. https://doi.org/10.1007/s11064-021-03418-7
doi: 10.1007/s11064-021-03418-7 pubmed: 34386919
Thornberry NA, Rano TA, Peterson EP, Rasper DM, Timkey T, Garcia-Calvo M, Houtzager VM, Nordstrom PA et al (1997) A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J Biol Chem 272(29):17907–17911. https://doi.org/10.1074/jbc.272.29.17907
Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, Alnemri ES, Altucci L et al (2018) Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 25(3):486–541. https://doi.org/10.1038/s41418-017-0012-4
doi: 10.1038/s41418-017-0012-4 pubmed: 29362479 pmcid: 5864239
Wnuk A, Kajta M (2017) Steroid and xenobiotic receptor signalling in apoptosis and autophagy of the nervous system. Int J Mol Sci 18(11):2394. https://doi.org/10.3390/ijms18112394
doi: 10.3390/ijms18112394 pubmed: 29137141 pmcid: 5713362
Dhage PA, Sharbidre AA, Magdum SM (2023) Interlacing the relevance of caspase activation in the onset and progression of Alzheimer’s disease. Brain Res Bull 192:83–92. https://doi.org/10.1016/j.brainresbull.2022.11.008
doi: 10.1016/j.brainresbull.2022.11.008 pubmed: 36372374
Gervais FG, Xu D, Robertson GS, Vaillancourt JP, Zhu Y, Huang J, LeBlanc A, Smith D et al (1999) Involvement of caspases in proteolytic cleavage of Alzheimer’s amyloid-beta precursor protein and amyloidogenic A beta peptide formation. Cell 97(3):395–406. https://doi.org/10.1016/s0092-8674(00)80748-5
doi: 10.1016/s0092-8674(00)80748-5 pubmed: 10319819
Plouffe V, Mohamed NV, Rivest-McGraw J, Bertrand J, Lauzon M, Leclerc N (2012) Hyperphosphorylation and cleavage at D421 enhance tau secretion. PLoS ONE 7(5):e36873. https://doi.org/10.1371/journal.pone.0036873
doi: 10.1371/journal.pone.0036873 pubmed: 22615831 pmcid: 3352936
Zhou Y, Shi J, Chu D, Hu W, Guan Z, Gong CX, Iqbal K, Liu F (2018) Relevance of phosphorylation and truncation of tau to the etiopathogenesis of Alzheimer’s disease. Front Aging Neurosci 10:27. https://doi.org/10.3389/fnagi.2018.00027
doi: 10.3389/fnagi.2018.00027 pubmed: 29472853 pmcid: 5810298
Park G, Nhan HS, Tyan SH, Kawakatsu Y, Zhang C, Navarro M, Koo EH (2020) Caspase activation and caspase-mediated cleavage of APP is associated with amyloid β-protein-induced synapse loss in Alzheimer’s disease. Cell Rep 31(13):107839. https://doi.org/10.1016/j.celrep.2020.107839
doi: 10.1016/j.celrep.2020.107839 pubmed: 32610140 pmcid: 7375398
Pérez MJ, Vergara-Pulgar K, Jara C, Cabezas-Opazo F, Quintanilla RA (2018) Caspase-cleaved tau impairs mitochondrial dynamics in Alzheimer’s disease. Mol Neurobiol 55(2):1004–1018. https://doi.org/10.1007/s12035-017-0385-x
doi: 10.1007/s12035-017-0385-x pubmed: 28084594
Nguyen TTM, Gillet G, Popgeorgiev N (2021) Caspases in the developing central nervous system: apoptosis and beyond. Front Cell Dev Biol 9:702404. https://doi.org/10.3389/fcell.2021.702404
doi: 10.3389/fcell.2021.702404 pubmed: 34336853 pmcid: 8322698
Hollville E, Deshmukh M (2018) Physiological functions of non-apoptotic caspase activity in the nervous system. Semin Cell Dev Biol 82:127–136. https://doi.org/10.1016/j.semcdb.2017.11.037
doi: 10.1016/j.semcdb.2017.11.037 pubmed: 29199140
Knopman DS, Amieva H, Petersen RC, Chételat G, Holtzman DM, Hyman BT, Nixon RA, Jones DT (2021) Alzheimer disease. Nat Rev Dis Primers 7(1):33. https://doi.org/10.1038/s41572-021-00269-y
doi: 10.1038/s41572-021-00269-y pubmed: 33986301 pmcid: 8574196
Rohn TT, Head E (2009) Caspases as therapeutic targets in Alzheimer’s disease: is it time to “cut” to the chase? Int J Clin Exp Pathol 2(2):108–118
pubmed: 19079646
Wnuk A, Przepiórska K, Pietrzak BA, Kajta M (2023) Emerging evidence on membrane estrogen receptors as novel therapeutic targets for central nervous system pathologies. Int J Mol Sci 24(4):4043. https://doi.org/10.3390/ijms24044043
doi: 10.3390/ijms24044043 pubmed: 36835454 pmcid: 9968034
Madak-Erdogan Z, Kim SH, Gong P, Zhao YC, Zhang H, Chambliss KL, Carlson KE, Mayne CG et al (2016) Design of pathway preferential estrogens that provide beneficial metabolic and vascular effects without stimulating reproductive tissues. Sci Signal 9(429):ra53. https://doi.org/10.1126/scisignal.aad8170
doi: 10.1126/scisignal.aad8170 pubmed: 27221711 pmcid: 4896643
Selvaraj UM, Zuurbier KR, Whoolery CW, Plautz EJ, Chambliss KL, Kong X, Zhang S, Kim SH et al (2018) Selective nonnuclear estrogen receptor activation decreases stroke severity and promotes functional recovery in female mice. Endocrinology 159(11):3848–3859. https://doi.org/10.1210/en.2018-00600
doi: 10.1210/en.2018-00600 pubmed: 30256928 pmcid: 6203892
Wnuk A, Przepiórska K, Pietrzak BA, Kajta M (2021) Posttreatment strategy against hypoxia and ischemia based on selective targeting of nonnuclear estrogen receptors with PaPE-1. Neurotox Res 39(6):2029–2041. https://doi.org/10.1007/s12640-021-00441-y
doi: 10.1007/s12640-021-00441-y pubmed: 34797527 pmcid: 8639538
Wnuk A, Przepiórska K, Rzemieniec J, Pietrzak B, Kajta M (2020) Selective targeting of non-nuclear estrogen receptors with PaPE-1 as a new treatment strategy for Alzheimer’s disease. Neurotox Res 38(4):957–966. https://doi.org/10.1007/s12640-020-00289-8
doi: 10.1007/s12640-020-00289-8 pubmed: 33025361 pmcid: 7591444
Kajta M, Trotter A, Lasoń W, Beyer C (2006) Impact of 17beta-estradiol on cytokine-mediated apoptotic effects in primary hippocampal and neocortical cell cultures. Brain Res 1116(1):64–74. https://doi.org/10.1016/j.brainres.2006.07.105
doi: 10.1016/j.brainres.2006.07.105 pubmed: 16949056
Przepiórska K, Wnuk A, Beyer C, Kajta M (2023) Amorfrutin B protects mouse brain neurons from hypoxia/ischemia by inhibiting apoptosis and autophagy processes through gene methylation- and miRNA-dependent regulation. Mol Neurobiol 60(2):576–595. https://doi.org/10.1007/s12035-022-03087-9
doi: 10.1007/s12035-022-03087-9 pubmed: 36324052
Kajta M, Litwa E, Rzemieniec J, Wnuk A, Lason W, Zelek-Molik A, Nalepa I, Grzegorzewska-Hiczwa M et al (2014) Isomer-nonspecific action of dichlorodiphenyltrichloroethane on aryl hydrocarbon receptor and G-protein-coupled receptor 30 intracellular signaling in apoptotic neuronal cells. Mol Cell Endocrinol 392(1–2):90–105. https://doi.org/10.1016/j.mce.2014.05.008
doi: 10.1016/j.mce.2014.05.008 pubmed: 24859647
Kajta M, Domin H, Grynkiewicz G, Lason W (2007) Genistein inhibits glutamate-induced apoptotic processes in primary neuronal cell cultures: an involvement of aryl hydrocarbon receptor and estrogen receptor/glycogen synthase kinase-3beta intracellular signaling pathway. Neuroscience 145(2):592–604. https://doi.org/10.1016/j.neuroscience.2006.11.059
doi: 10.1016/j.neuroscience.2006.11.059 pubmed: 17261353
Kajta M, Wójtowicz AK, Maćkowiak M, Lasoń W (2009) Aryl hydrocarbon receptor-mediated apoptosis of neuronal cells: a possible interaction with estrogen receptor signaling. Neuroscience 158(2):811–822. https://doi.org/10.1016/j.neuroscience.2008.10.045
doi: 10.1016/j.neuroscience.2008.10.045 pubmed: 19027052
Wnuk A, Rzemieniec J, Litwa E, Lasoń W, Krzeptowski W, Wójtowicz AK, Kajta M (2016) The crucial involvement of retinoid X receptors in DDE neurotoxicity. Neurotox Res 29(1):155–172. https://doi.org/10.1007/s12640-015-9572-6
doi: 10.1007/s12640-015-9572-6 pubmed: 26563996
Wnuk A, Rzemieniec J, Lasoń W, Krzeptowski W, Kajta M (2018) Apoptosis induced by the UV filter benzophenone-3 in mouse neuronal cells is mediated via attenuation of Erα/Pparγ and stimulation of Erβ/Gpr30 signaling. Mol Neurobiol 55(3):2362–2383. https://doi.org/10.1007/s12035-017-0480-z
doi: 10.1007/s12035-017-0480-z pubmed: 28357806
Rzemieniec J, Litwa E, Wnuk A, Lason W, Krzeptowski W, Kajta M (2016) Selective aryl hydrocarbon receptor modulator 3,3′-diindolylmethane impairs AhR and ARNT signaling and protects mouse neuronal cells against hypoxia. Mol Neurobiol 53(8):5591–5606. https://doi.org/10.1007/s12035-015-9471-0
doi: 10.1007/s12035-015-9471-0 pubmed: 26476840
Wnuk A, Rzemieniec J, Lasoń W, Krzeptowski W, Kajta M (2018) Benzophenone-3 impairs autophagy, alters epigenetic status, and disrupts retinoid X receptor signaling in apoptotic neuronal cells. Mol Neurobiol 55(6):5059–5074. https://doi.org/10.1007/s12035-017-0704-2
doi: 10.1007/s12035-017-0704-2 pubmed: 28815487
Wnuk A, Rzemieniec J, Przepiórska K, Pietrzak BA, Maćkowiak M, Kajta M (2021) Prenatal exposure to triclocarban impairs ESR1 signaling and disrupts epigenetic status in sex-specific ways as well as dysregulates the expression of neurogenesis- and neurotransmitter-related genes in the postnatal mouse brain. Int J Mol Sci 22(23):13121. https://doi.org/10.3390/ijms222313121
doi: 10.3390/ijms222313121 pubmed: 34884933 pmcid: 8658534
Wnuk A, Przepiórska K, Pietrzak BA, Kajta M (2021) Post-treatment with amorfrutin B evokes PPARγ-mediated neuroprotection against hypoxia and ischemia. Biomedicines 9(8):854. https://doi.org/10.3390/biomedicines9080854
doi: 10.3390/biomedicines9080854 pubmed: 34440058 pmcid: 8389580
Kajta M, Rzemieniec J, Litwa E, Lason W, Lenartowicz M, Krzeptowski W, Wojtowicz AK (2013) The key involvement of estrogen receptor β and G-protein-coupled receptor 30 in the neuroprotective action of daidzein. Neuroscience 238:345–360. https://doi.org/10.1016/j.neuroscience.2013.02.005
doi: 10.1016/j.neuroscience.2013.02.005 pubmed: 23419549
Pietrzak BA, Wnuk A, Przepiórska K, Łach A, Kajta M (2023) Posttreatment with ospemifene attenuates hypoxia- and ischemia-induced apoptosis in primary neuronal cells via selective modulation of estrogen receptors. Neurotox Res. https://doi.org/10.1007/s12640-023-00644-5
doi: 10.1007/s12640-023-00644-5 pubmed: 37129835 pmcid: 10354152
Hampel H, Hardy J, Blennow K, Chen C, Perry G, Kim SH, Villemagne VL, Aisen P et al (2021) The amyloid-β pathway in Alzheimer’s disease. Mol Psychiatry 26(10):5481–5503. https://doi.org/10.1038/s41380-021-01249-0
doi: 10.1038/s41380-021-01249-0 pubmed: 34456336 pmcid: 8758495
Daoutsali E, Pepers BA, Stamatakis S, van der Graaf LM, Terwindt GM, Parfitt DA, Buijsen RAM, van Roon-Mom WMC (2023) Amyloid beta accumulations and enhanced neuronal differentiation in cerebral organoids of Dutch-type cerebral amyloid angiopathy patients. Front Aging Neurosci 14:1048584. https://doi.org/10.3389/fnagi.2022.1048584
doi: 10.3389/fnagi.2022.1048584 pubmed: 36733499 pmcid: 9887998
Ferreira A, Sinjoanu RC, Nicholson A, Kleinschmidt S (2011) Aβ toxicity in primary cultured neurons. Methods Mol Biol (Clifton, N.J.) 670:141–153. https://doi.org/10.1007/978-1-60761-744-0_11
doi: 10.1007/978-1-60761-744-0_11
Roos TT, Garcia MG, Martinsson I, Mabrouk R, Israelsson B, Deierborg T, Kobro-Flatmoen A, Tanila H et al (2021) Neuronal spreading and plaque induction of intracellular Aβ and its disruption of Aβ homeostasis. Acta Neuropathol 142(4):669–687. https://doi.org/10.1007/s00401-021-02345-9
doi: 10.1007/s00401-021-02345-9 pubmed: 34272583 pmcid: 8423700
Kwakowsky A, Potapov K, Kim S, Peppercorn K, Tate WP, Ábrahám IM (2016) Treatment of beta amyloid 1–42 (Aβ(1–42))-induced basal forebrain cholinergic damage by a non-classical estrogen signaling activator in vivo. Sci Rep 6:21101. https://doi.org/10.1038/srep21101
doi: 10.1038/srep21101 pubmed: 26879842 pmcid: 4754683
Wang YX, Xia ZH, Jiang X, Li LX, Wang HG, An D, Liu YQ (2020) Genistein inhibits amyloid peptide 25–35-induced neuronal death by modulating estrogen receptors, choline acetyltransferase and glutamate receptors. Arch Biochem Biophys 693:108561. https://doi.org/10.1016/j.abb.2020.108561
doi: 10.1016/j.abb.2020.108561 pubmed: 32857999
Duan X, Li Y, Xu F, Ding H (2021) Study on the neuroprotective effects of Genistein on Alzheimer’s disease. Brain Behav 11(5):e02100. https://doi.org/10.1002/brb3.2100
doi: 10.1002/brb3.2100 pubmed: 33704934 pmcid: 8119804
Zhao L, Woody SK, Chhibber A (2015) Estrogen receptor β in Alzheimer’s disease: from mechanisms to therapeutics. Ageing Res Rev 24(Pt B):178–190. https://doi.org/10.1016/j.arr.2015.08.001
doi: 10.1016/j.arr.2015.08.001 pubmed: 26307455 pmcid: 4661108
Qin C, Hu S, Zhang S, Zhao D, Wang Y, Li H, Peng Y, Shi L et al (2021) Hydroxytyrosol acetate improves the cognitive function of APP/PS1 transgenic mice in ERβ-dependent manner. Mol Nutr Food Res 65(3):e2000797. https://doi.org/10.1002/mnfr.202000797
doi: 10.1002/mnfr.202000797 pubmed: 33296142
Wang Y, Hernandez G, Mack WJ, Schneider LS, Yin F, Brinton RD (2020) Retrospective analysis of phytoSERM for management of menopause-associated vasomotor symptoms and cognitive decline: a pilot study on pharmacogenomic effects of mitochondrial haplogroup and APOE genotype on therapeutic efficacy. Menopause (New York, NY) 27(1):57–65. https://doi.org/10.1097/GME.0000000000001418
doi: 10.1097/GME.0000000000001418
Liu J, Yuan S, Niu X, Kelleher R, Sheridan H (2022) ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer’s disease process. Aging 14(21):8595–8614. https://doi.org/10.18632/aging.204359
doi: 10.18632/aging.204359 pubmed: 36326669 pmcid: 9699767
Calissano P, Matrone C, Amadoro G (2009) Apoptosis and in vitro Alzheimer disease neuronal models. Commun Integr Biol 2(2):163–169. https://doi.org/10.4161/cib.7704
doi: 10.4161/cib.7704 pubmed: 19513272 pmcid: 2686374
Wilkins HM, Mahnken JD, Welch P, Bothwell R, Koppel S, Jackson RL, Burns JM, Swerdlow RH (2017) A mitochondrial biomarker-based study of S-equol in Alzheimer’s disease subjects: results of a single-arm, pilot trial. J Alzheimer’s Dis 59(1):291–300. https://doi.org/10.3233/JAD-170077
doi: 10.3233/JAD-170077
Ren XQ, Huang X, Xing SY, Long Y, Yuan DH, Hong H, Tang SS (2023) Neuroprotective effects of novel compound FMDB on cognition, neurogenesis and apoptosis in APP/PS1 transgenic mouse model of Alzheimer’s disease. Neurochem Int 165:105510. https://doi.org/10.1016/j.neuint.2023.105510
doi: 10.1016/j.neuint.2023.105510 pubmed: 36893915
Shi C, Zhu X, Wang J, Long D (2014) Estrogen receptor α promotes non-amyloidogenic processing of platelet amyloid precursor protein via the MAPK/ERK pathway. J Steroid Biochem Mol Biol 144 Pt B:280–285. https://doi.org/10.1016/j.jsbmb.2014.06.010
doi: 10.1016/j.jsbmb.2014.06.010 pubmed: 25017047
Yan X, Hu G, Yan W, Chen T, Yang F, Zhang X, Zhao G, Liu J (2017) Ginsenoside Rd promotes non-amyloidogenic pathway of amyloid precursor protein processing by regulating phosphorylation of estrogen receptor alpha. Life Sci 168:16–23. https://doi.org/10.1016/j.lfs.2016.11.002
doi: 10.1016/j.lfs.2016.11.002 pubmed: 27825720
Tamayev R, Akpan N, Arancio O, Troy CM, D’Adamio L (2012) Caspase-9 mediates synaptic plasticity and memory deficits of Danish dementia knock-in mice: caspase-9 inhibition provides therapeutic protection. Mol Neurodegener 7:60. https://doi.org/10.1186/1750-1326-7-60
doi: 10.1186/1750-1326-7-60 pubmed: 23217200 pmcid: 3543220
Zhou HH, Luo L, Zhai XD, Chen L, Wang G, Qin LQ, Yu Z, Xin LL et al (2021) Sex-specific neurotoxicity of dietary advanced glycation end products in APP/PS1 mice and protective roles of trehalose by inhibiting tau phosphorylation via GSK-3β-TFEB. Mol Nutr Food Res 65(23):e2100464. https://doi.org/10.1002/mnfr.202100464
doi: 10.1002/mnfr.202100464 pubmed: 34669246
Zeng M, Feng A, Zhao C, Zhang B, Guo P, Liu M, Zhang Q, Zhang Y, Fan R, Lyu J, Zheng X (2022) Adenosine ameliorated Aβ
doi: 10.1016/j.brainres.2022.147944 pubmed: 35568086
Xiao H, Qin X, Wan J, Li R (2019) Pharmacological targets and the biological mechanisms of formononetin for Alzheimer’s disease: a network analysis. Med Sci Monitor 25:4273–4277. https://doi.org/10.12659/MSM.916662
doi: 10.12659/MSM.916662
Zhang N, Hu Z, Zhang Z, Liu G, Wang Y, Ren Y, Wu X, Geng F (2018) Protective role of naringenin against Aβ
doi: 10.1007/s10571-017-0519-8 pubmed: 28699113
Satou T, Cummings BJ, Cotman CW (1995) Immunoreactivity for Bcl-2 protein within neurons in the Alzheimer’s disease brain increases with disease severity. Brain Res 697(1–2):35–43. https://doi.org/10.1016/0006-8993(95)00748-f
doi: 10.1016/0006-8993(95)00748-f pubmed: 8593592
O’Barr S, Schultz J, Rogers J (1996) Expression of the protooncogene bcl-2 in Alzheimer’s disease brain. Neurobiol Aging 17(1):131–136. https://doi.org/10.1016/0197-4580(95)02024-1
doi: 10.1016/0197-4580(95)02024-1 pubmed: 8786795
Kitamura Y, Shimohama S, Kamoshima W, Ota T, Matsuoka Y, Nomura Y, Smith MA, Perry G et al (1998) Alteration of proteins regulating apoptosis, Bcl-2, Bcl-x, Bax, Bak, Bad, ICH-1 and CPP32. Alzheimer’s Dis Brain Res 780(2):260–269. https://doi.org/10.1016/s0006-8993(97)01202-x
doi: 10.1016/s0006-8993(97)01202-x
Callens M, Kraskovskaya N, Derevtsova K, Annaert W, Bultynck G, Bezprozvanny I, Vervliet T (2021) The role of Bcl-2 proteins in modulating neuronal Ca

Auteurs

Bernadeta A Pietrzak-Wawrzyńska (BA)

Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343, Krakow, Poland.

Agnieszka Wnuk (A)

Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343, Krakow, Poland.

Karolina Przepiórska-Drońska (K)

Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343, Krakow, Poland.

Andrzej Łach (A)

Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343, Krakow, Poland.

Małgorzata Kajta (M)

Laboratory of Neuropharmacology and Epigenetics, Department of Pharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, Smetna Street 12, 31-343, Krakow, Poland. kajta@if-pan.krakow.pl.

Classifications MeSH