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Endocrine, Metabolic & Immune Disorders - Drug Targets

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ISSN (Print): 1871-5303
ISSN (Online): 2212-3873

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Research Article

Neuroimmune Dysregulation in Prepubertal and Adolescent Individuals Affected by Klinefelter Syndrome

Author(s): Luigi Tarani, Flavio Maria Ceci, Valentina Carito, Giampiero Ferraguti, Carla Petrella, Antonio Greco, Massimo Ralli, Antonio Minni, Matteo Spaziani, Andrea M. Isidori, Maria Grazia Di Certo, Christian Barbato, Carolina Putotto and Marco Fiore*

Volume 23, Issue 1, 2023

Published on: 10 October, 2022

Page: [105 - 114] Pages: 10

DOI: 10.2174/1871530322666220704101310

Price: $65

Abstract

Background: The syndrome Klinefelter syndrome (KS) is a genetic disorder due to an extra X chromosome in males. Many cases remain undiagnosed until the onset of major manifestations, which include hypergonadotropic hypogonadism and infertility. This condition is associated with many comorbidities that involve the cardiovascular, endocrine, and immune systems. Last but not the least, individuals with KS show a high risk of developing psychiatric and mood disorders in adult age.

Objective: While many studies are accessible on KS in adult individuals, the neuroinflammatory condition in adolescent and prepubertal KS individuals is not fully known.

Methods: Our study aims to evaluate in prepubertal and adolescent KS individuals, for the first time, the levels of the serum of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), cytokines having subtle roles in oxidative processes, and neuroinflammation with respect to the levels of TNF-α, TGF-β, MCP-1, IL-1α, IL-2, IL-6, IL-10, and IL-12 and oxidative stress by employing free oxygen radicals defense and free oxygen radicals test.

Results:We found no changes in NGF and oxidative stress parameters, but BDNF decreased compared to healthy children. Quite interestingly, our data showed reduced levels of IL-2, IL-1α, IL- 12, IL-10, and IL-6 in prepubertal KS children.

Conclusion: The present study discloses disrupted immune system and neurotrophin pathways in KS children.

Keywords: Gender, NGF, BDNF, Klinefelter syndrome, neuroinflammation, oxidative stress, interleukin.

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[1]
Groth, K.A.; Skakkebæk, A.; Høst, C.; Gravholt, C.H.; Bojesen, A. Clinical review: Klinefelter syndrome-a clinical update. J. Clin. Endocrinol. Metab., 2013, 98(1), 20-30.
[http://dx.doi.org/10.1210/jc.2012-2382] [PMID: 23118429]
[2]
Davis, S.M.; Ross, J.L. Klinefelter syndrome. In: Encyclopedia of Endocrine Diseases; Huhtaniemi, I.; Martini, L., Eds.; Academic Press: Cambridge, Massachusetts, 2018; pp. 561-567.
[http://dx.doi.org/10.1016/B978-0-12-801238-3.66137-8]
[3]
Chang, S.; Skakkebæk, A.; Gravholt, C.H. Klinefelter syndrome and medical treatment: Hypogonadism and beyond. Hormones (Athens), 2015, 14(4), 531-548.
[http://dx.doi.org/10.14310/horm.2002.1622] [PMID: 26732150]
[4]
Bojesen, A.; Juul, S.; Gravholt, C.H. Prenatal and postnatal prevalence of Klinefelter syndrome: A national registry study. J. Clin. Endocrinol. Metab., 2003, 88(2), 622-626.
[http://dx.doi.org/10.1210/jc.2002-021491] [PMID: 12574191]
[5]
De Sanctis, V.; Ciccone, S. Fertility preservation in adolescents with Klinefelter’s syndrome. Pediatr. Endocrinol. Rev., 2010, 8(Suppl. 1), 178-181.
[PMID: 21217610]
[6]
Staessen, C.; Tournaye, H.; Van Assche, E.; Michiels, A.; Van Landuyt, L.; Devroey, P.; Liebaers, I.; Van Steirteghem, A. PGD in 47,XXY Klinefelter’s syndrome patients. Hum. Reprod. Update, 2003, 9(4), 319-330.
[http://dx.doi.org/10.1093/humupd/dmg029] [PMID: 12926526]
[7]
Giltay, J.C.; Maiburg, M.C. Klinefelter syndrome: Clinical and molecular aspects. Expert Rev. Mol. Diagn., 2010, 10(6), 765-776.
[http://dx.doi.org/10.1586/erm.10.63] [PMID: 20843200]
[8]
Visootsak, J.; Graham, J.M., Jr Klinefelter syndrome and other sex chromosomal aneuploidies. Orphanet J. Rare Dis., 2006, 1(1), 42.
[http://dx.doi.org/10.1186/1750-1172-1-42] [PMID: 17062147]
[9]
Tüttelmann, F.; Gromoll, J. Novel genetic aspects of Klinefelter’s syndrome. Mol. Hum. Reprod., 2010, 16(6), 386-395.
[http://dx.doi.org/10.1093/molehr/gaq019] [PMID: 20228051]
[10]
Deebel, N.A.; Bradshaw, A.W.; Sadri-Ardekani, H. Infertility considerations in Klinefelter syndrome: From origin to management. Best Pract. Res. Clin. Endocrinol. Metab., 2020, 34(6), 101480.
[http://dx.doi.org/10.1016/j.beem.2020.101480] [PMID: 33358481]
[11]
Nieschlag, E.; Werler, S.; Wistuba, J.; Zitzmann, M. New approaches to the Klinefelter syndrome. Ann. Endocrinol. (Paris), 2014, 75(2), 88-97.
[http://dx.doi.org/10.1016/j.ando.2014.03.007] [PMID: 24793990]
[12]
Høst, C.; Skakkebæk, A.; Groth, K.A.; Bojesen, A. The role of hypogonadism in Klinefelter syndrome. Asian J. Androl., 2014, 16(2), 185-191.
[http://dx.doi.org/10.4103/1008-682X.122201] [PMID: 24407186]
[13]
Spaziani, M.; Radicioni, A.F. Metabolic and cardiovascular risk factors in Klinefelter syndrome. Am. J. Med. Genet. C. Semin. Med. Genet., 2020, 184(2), 334-343.
[http://dx.doi.org/10.1002/ajmg.c.31792] [PMID: 32452627]
[14]
Leggett, V.; Jacobs, P.; Nation, K.; Scerif, G.; Bishop, D.V.M. Neurocognitive outcomes of individuals with a sex chromosome trisomy: XXX, XYY, or XXY: A systematic review. Dev. Med. Child Neurol., 2010, 52(2), 119-129.
[http://dx.doi.org/10.1111/j.1469-8749.2009.03545.x] [PMID: 20059514]
[15]
Lanfranco, F.; Kamischke, A.; Zitzmann, M.; Nieschlag, E. Klinefelter’s syndrome. Lancet, 2004, 364(9430), 273-283.
[http://dx.doi.org/10.1016/S0140-6736(04)16678-6] [PMID: 15262106]
[16]
Karipidis, I.I.; Hong, D.S. Specific learning disorders in sex chromosome aneuploidies: Neural circuits of literacy and mathematics. Am. J. Med. Genet. C. Semin. Med. Genet., 2020, 184(2), 518-530.
[http://dx.doi.org/10.1002/ajmg.c.31801] [PMID: 32463563]
[17]
van Rijn, S.; Aleman, A.; Swaab, H.; Kahn, R.S. Neurobiology of emotion and high risk for schizophrenia: Role of the amygdala and the X-chromosome. Neurosci. Biobehav. Rev., 2005, 29(3), 385-397.
[http://dx.doi.org/10.1016/j.neubiorev.2004.11.005] [PMID: 15820545]
[18]
Tarani, L.; Rasio, D.; Tarani, F.; Parlapiano, G.; Valentini, D.; Dylag, K.A.; Spalice, A.; Paparella, R.; Fiore, M. Pediatrics of disability: A comprehensive approach to the child with syndromic psychomotor delay. Curr. Pediatr. Rev., 2021, 17.
[http://dx.doi.org/10.2174/1573396317666211129093426] [PMID: 34844545]
[19]
Radicioni, A.F.; Ferlin, A.; Balercia, G.; Pasquali, D.; Vignozzi, L.; Maggi, M.; Foresta, C.; Lenzi, A. Consensus statement on diagnosis and clinical management of Klinefelter syndrome. J. Endocrinol. Invest., 2010, 33(11), 839-850.
[http://dx.doi.org/10.1007/BF03350351] [PMID: 21293172]
[20]
Eleje, G.U.; Ikechebelu, J.I. Klinefelter’s syndrome in an adolescent. Gynecol. Cases Rev, 2014, 1.
[21]
Martin, S.; Cordeiro, L.; Richardson, P.; Davis, S.; Tartaglia, N. The association of motor skills and adaptive functioning in XXY/Klinefelter and XXYY Syndromes. Phys. Occup. Ther. Pediatr., 2019, 39(4), 446-459.
[http://dx.doi.org/10.1080/01942638.2018.1541040] [PMID: 30592247]
[22]
Seminog, O.O.; Seminog, A.B.; Yeates, D.; Goldacre, M.J. Associations between Klinefelter’s syndrome and autoimmune diseases: English national record linkage studies. Autoimmunity, 2015, 48(2), 125-128.
[http://dx.doi.org/10.3109/08916934.2014.968918] [PMID: 25295757]
[23]
Calogero, A.E.; Giagulli, V.A.; Mongioì, L.M.; Triggiani, V.; Radicioni, A.F.; Jannini, E.A.; Pasquali, D. Klinefelter syndrome: Cardiovascular abnormalities and metabolic disorders. J. Endocrinol. Invest., 2017, 40(7), 705-712.
[http://dx.doi.org/10.1007/s40618-017-0619-9] [PMID: 28258556]
[24]
Kanakis, G.A.; Nieschlag, E. Klinefelter syndrome: More than hypogonadism. Metabolism, 2018, 86, 135-144.
[http://dx.doi.org/10.1016/j.metabol.2017.09.017] [PMID: 29382506]
[25]
Savic, I. Advances in research on the neurological and neuropsychiatric phenotype of Klinefelter syndrome. Curr. Opin. Neurol., 2012, 25(2), 138-143.
[http://dx.doi.org/10.1097/WCO.0b013e32835181a0] [PMID: 22395004]
[26]
Iulita, M.F.; Cuello, A.C. The NGF metabolic pathway in the CNS and its dysregulation in down syndrome and Alzheimer’s disease. Curr. Alzheimer Res., 2016, 13(1), 53-67.
[http://dx.doi.org/10.2174/1567205012666150921100030] [PMID: 26391047]
[27]
Tarani, L.; Carito, V.; Ferraguti, G.; Petrella, C.; Greco, A.; Ralli, M.; Messina, M.P.; Rasio, D.; De Luca, E.; Putotto, C.; Versacci, P.; Ceccanti, M.; Fiore, M. Neuroinflammatory markers in the serum of prepubertal children with Down syndrome. J. Immunol. Res., 2020, 2020, 6937154.
[http://dx.doi.org/10.1155/2020/6937154] [PMID: 32280719]
[28]
Castrén, M.L.; Castrén, E. BDNF in fragile X syndrome. Neuropharmacology, 2014, 76(Pt C), 729-736.
[http://dx.doi.org/10.1016/j.neuropharm.2013.05.018] [PMID: 23727436]
[29]
Ceci, F.M.; Ferraguti, G.; Petrella, C.; Greco, A.; Tirassa, P.; Iannitelli, A.; Ralli, M.; Vitali, M.; Ceccanti, M.; Chaldakov, G.N.; Versacci, P.; Fiore, M. Nerve growth factor, stress and diseases. Curr. Med. Chem., 2021, 28(15), 2943-2959.
[http://dx.doi.org/10.2174/0929867327999200818111654] [PMID: 32811396]
[30]
Fields, J.; Dumaop, W.; Langford, T.D.; Rockenstein, E.; Masliah, E. Role of neurotrophic factor alterations in the neurodegenerative process in HIV associated neurocognitive disorders. J. Neuroimmune Pharmacol., 2014, 9(2), 102-116.
[http://dx.doi.org/10.1007/s11481-013-9520-2] [PMID: 24510686]
[31]
Bruscolini, A.; Sacchetti, M.; La Cava, M.; Nebbioso, M.; Iannitelli, A.; Quartini, A.; Lambiase, A.; Ralli, M.; de Virgilio, A.; Greco, A. Quality of life and neuropsychiatric disorders in patients with Graves’ Orbitopathy: Current concepts. Autoimmun. Rev., 2018, 17(7), 639-643.
[http://dx.doi.org/10.1016/j.autrev.2017.12.012] [PMID: 29729448]
[32]
Quartini, A.; Pacitti, F.; Bersani, G.; Iannitelli, A. From adolescent neurogenesis to schizophrenia: Opportunities, challenges and promising interventions. Biomed. Rev., 2017, 28(0), 66-73.
[http://dx.doi.org/10.14748/bmr.v28.4452]
[33]
Schulte-Herbrüggen, O.; Braun, A.; Rochlitzer, S.; Jockers-Scherübl, M.C.; Hellweg, R. Neurotrophic factors-a tool for therapeutic strategies in neurological, neuropsychiatric and neuroimmunological diseases? Curr. Med. Chem., 2007, 14(22), 2318-2329.
[http://dx.doi.org/10.2174/092986707781745578] [PMID: 17896980]
[34]
Aloe, L.; Skaper, S.D.; Leon, A.; Levi-Montalcini, R. Nerve growth factor and autoimmune diseases. Autoimmunity, 1994, 19(2), 141-150.
[http://dx.doi.org/10.3109/08916939409009542] [PMID: 7772704]
[35]
Ciafrè, S.; Ferraguti, G.; Greco, A.; Polimeni, A.; Ralli, M.; Ceci, F.M.; Ceccanti, M.; Fiore, M. Alcohol as an early life stressor: Epigenetics, metabolic, neuroendocrine and neurobehavioral implications. Neurosci. Biobehav. Rev., 2020, 118, 654-668.
[http://dx.doi.org/10.1016/j.neubiorev.2020.08.018] [PMID: 32976915]
[36]
Carito, V.; Ceccanti, M.; Ferraguti, G.; Coccurello, R.; Ciafrè, S.; Tirassa, P.; Fiore, M. NGF and BDNF alterations by prenatal alcohol exposure. Curr. Neuropharmacol., 2019, 17(4), 308-317.
[http://dx.doi.org/10.2174/1570159X15666170825101308] [PMID: 28847297]
[37]
Vega, S.R.; Kleinert, J.; Sulprizio, M.; Hollmann, W.; Bloch, W.; Strüder, H.K. Responses of serum neurotrophic factors to exercise in pregnant and postpartum women. Psychoneuroendocrinology, 2011, 36(2), 220-227.
[http://dx.doi.org/10.1016/j.psyneuen.2010.07.012] [PMID: 20692101]
[38]
Mondal, A.C.; Fatima, M. Direct and indirect evidences of BDNF and NGF as key modulators in depression: Role of antidepressants treatment. Int. J. Neurosci., 2019, 129(3), 283-296.
[http://dx.doi.org/10.1080/00207454.2018.1527328] [PMID: 30235967]
[39]
Tore, F.; Tonchev, A.; Fiore, M.; Tuncel, N.; Atanassova, P.; Aloe, L.; Chaldakov, G. From adipose tissue protein secretion to adipopharmacology of disease. Immunol. Endocr. Metab. Agents Med. Chem., 2007, 7(2), 149-155.
[http://dx.doi.org/10.2174/187152207780363712]
[40]
Budni, J.; Bellettini-Santos, T.; Mina, F.; Garcez, M.L.; Zugno, A.I. The involvement of BDNF, NGF and GDNF in aging and Alzheimer’s disease. Aging Dis., 2015, 6(5), 331-341.
[http://dx.doi.org/10.14336/AD.2015.0825] [PMID: 26425388]
[41]
Miranda, M.; Morici, J.F.; Zanoni, M.B.; Bekinschtein, P. Brain-derived neurotrophic factor: A key molecule for memory in the healthy and the pathological brain. Front. Cell. Neurosci., 2019, 13, 363.
[http://dx.doi.org/10.3389/fncel.2019.00363] [PMID: 31440144]
[42]
Bianchi, I.; Lleo, A.; Gershwin, M.E.; Invernizzi, P. The X chromosome and immune associated genes. J. Autoimmun., 2012, 38(2-3), J187-J192.
[http://dx.doi.org/10.1016/j.jaut.2011.11.012] [PMID: 22178198]
[43]
Gravholt, C.H.; Jensen, A.S.; Høst, C.; Bojesen, A. Body composition, metabolic syndrome and type 2 diabetes in Klinefelter syndrome. Acta Paediatr., 2011, 100(6), 871-877.
[http://dx.doi.org/10.1111/j.1651-2227.2011.02233.x] [PMID: 21342256]
[44]
Lefèvre, N.; Corazza, F.; Valsamis, J.; Delbaere, A.; De Maertelaer, V.; Duchateau, J.; Casimir, G. The number of X chromosomes influences inflammatory cytokine production following Toll-like receptor stimulation. Front. Immunol., 2019, 10, 1052.
[http://dx.doi.org/10.3389/fimmu.2019.01052] [PMID: 31143188]
[45]
Rotondi, M.; Coperchini, F.; Renzullo, A.; Accardo, G.; Esposito, D.; Groppelli, G.; Magri, F.; Cittadini, A.; Isidori, A.M.; Chiovato, L.; Pasquali, D. High circulating levels of CCL2 in patients with Klinefelter’s syndrome. Clin. Endocrinol. (Oxf.), 2014, 80(3), 465-467.
[http://dx.doi.org/10.1111/cen.12245] [PMID: 23663065]
[46]
Bates, S.E. Classical cytogenetics: Karyotyping techniques. In: Human Pluripotent Stem Cells; Schwartz, P.; Wesselschmidt, R., Eds.; Humana Press: New York, 2011; pp. 177-190.
[http://dx.doi.org/10.1007/978-1-61779-201-4_13]
[47]
Thalhammer, S.; Koehler, U.; Stark, R.W.; Heckl, W.M. GTG banding pattern on human metaphase chromosomes revealed by high resolution atomic-force microscopy. J. Microsc., 2001, 202(Pt 3), 464-467.
[http://dx.doi.org/10.1046/j.1365-2818.2001.00909.x] [PMID: 11422667]
[48]
Huang, H.; Chen, J. Chromosome bandings. In: Cancer Cytogenetics; Wan, T., Ed.; Humana Press: New York, 2017; pp. 59-66.
[http://dx.doi.org/10.1007/978-1-4939-6703-2_6]
[49]
Fiore, M.; Tarani, L.; Radicioni, A.; Spaziani, M.; Ferraguti, G.; Putotto, C. Serum prokineticin-2 in prepubertal and adult Klinefelter individuals. Can. J. Physiol. Pharmacol., 2022, 100(2), 151-157.
[http://dx.doi.org/10.1139/cjpp-2021-0457] [PMID: 34614364]
[50]
Ceccanti, M.; Hamilton, D.; Coriale, G.; Carito, V.; Aloe, L.; Chaldakov, G.; Romeo, M.; Ceccanti, M.; Iannitelli, A.; Fiore, M. Spatial learning in men undergoing alcohol detoxification. Physiol. Behav., 2015, 149, 324-330.
[http://dx.doi.org/10.1016/j.physbeh.2015.06.034] [PMID: 26143187]
[51]
Ceccanti, M.; Coriale, G.; Hamilton, D.A.; Carito, V.; Coccurello, R.; Scalese, B.; Ciafrè, S.; Codazzo, C.; Messina, M.P.; Chaldakov, G.N.; Fiore, M. Virtual Morris task responses in individuals in an abstinence phase from alcohol. Can. J. Physiol. Pharmacol., 2018, 96(2), 128-136.
[http://dx.doi.org/10.1139/cjpp-2017-0013] [PMID: 28763626]
[52]
Spaziani, M.; Tarantino, C.; Tahani, N.; Gianfrilli, D.; Sbardella, E.; Lenzi, A.; Radicioni, A.F. Hypothalamo-Pituitary axis and puberty. Mol. Cell. Endocrinol., 2021, 520, 111094.
[http://dx.doi.org/10.1016/j.mce.2020.111094] [PMID: 33271219]
[53]
Carito, V.; Ceccanti, M.; Cestari, V.; Natella, F.; Bello, C.; Coccurello, R.; Mancinelli, R.; Fiore, M. Olive polyphenol effects in a mouse model of chronic ethanol addiction. Nutrition, 2017, 33, 65-69.
[http://dx.doi.org/10.1016/j.nut.2016.08.014] [PMID: 27908553]
[54]
Carito, V.; Venditti, A.; Bianco, A.; Ceccanti, M.; Serrilli, A.M.; Chaldakov, G.; Tarani, L.; De Nicolò, S.; Fiore, M. Effects of olive leaf polyphenols on male mouse brain NGF, BDNF and their receptors TrkA, TrkB and p75. Nat. Prod. Res., 2014, 28(22), 1970-1984.
[http://dx.doi.org/10.1080/14786419.2014.918977] [PMID: 24865115]
[55]
Angelucci, F.; Piermaria, J.; Gelfo, F.; Shofany, J.; Tramontano, M.; Fiore, M.; Caltagirone, C.; Peppe, A. The effects of motor rehabilitation training on clinical symptoms and serum BDNF levels in Parkinson’s disease subjects. Can. J. Physiol. Pharmacol., 2016, 94(4), 455-461.
[http://dx.doi.org/10.1139/cjpp-2015-0322] [PMID: 26863448]
[56]
Carito, V.; Ceccanti, M.; Tarani, L.; Ferraguti, G.; Chaldakov, G.N.; Fiore, M. Neurotrophins’ modulation by olive polyphenols. Curr. Med. Chem., 2016, 23(28), 3189-3197.
[http://dx.doi.org/10.2174/0929867323666160627104022] [PMID: 27356540]
[57]
Pavlatou, M.G.; Papastamataki, M.; Apostolakou, F.; Papassotiriou, I.; Tentolouris, N. FORT and FORD: Two simple and rapid assays in the evaluation of oxidative stress in patients with type 2 diabetes mellitus. Metabolism, 2009, 58(11), 1657-1662.
[http://dx.doi.org/10.1016/j.metabol.2009.05.022] [PMID: 19604518]
[58]
Spaziani, M.; Granato, S.; Liberati, N.; Rossi, F.M.; Tahani, N.; Pozza, C.; Gianfrilli, D.; Papi, G.; Anzuini, A.; Lenzi, A.; Tarani, L.; Radicioni, A.F. From mini-puberty to pre-puberty: Early impairment of the hypothalamus-pituitary-gonadal axis with normal testicular function in children with non-mosaic Klinefelter syndrome. J. Endocrinol. Invest., 2021, 44(1), 127-138.
[http://dx.doi.org/10.1007/s40618-020-01281-x] [PMID: 32378142]
[59]
Manni, L.; Aloe, L.; Fiore, M. Changes in cognition induced by social isolation in the mouse are restored by electro-acupuncture. Physiol. Behav., 2009, 98(5), 537-542.
[http://dx.doi.org/10.1016/j.physbeh.2009.08.011] [PMID: 19733189]
[60]
Fiore, M.; Triaca, V.; Amendola, T.; Tirassa, P.; Aloe, L. Brain NGF and EGF administration improves passive avoidance response and stimulates brain precursor cells in aged male mice. Physiol. Behav., 2002, 77(2-3), 437-443.
[http://dx.doi.org/10.1016/S0031-9384(02)00875-2] [PMID: 12419420]
[61]
Aitken, R.J.; Baker, M.A. The role of genetics and oxidative stress in the etiology of male infertility-a unifying hypothesis? Front. Endocrinol. (Lausanne), 2020, 11, 581838.
[http://dx.doi.org/10.3389/fendo.2020.581838] [PMID: 33101214]
[62]
Boschen, K.E.; Klintsova, A.Y. Neurotrophins in the brain: Interaction with alcohol exposure during development. Vitam. Horm., 2017, 104, 197-242.
[http://dx.doi.org/10.1016/bs.vh.2016.10.008] [PMID: 28215296]
[63]
Chaldakov, G.N.; Fiore, M.; Tonchev, A.B.; Aloe, L. Neuroadipology: A novel component of neuroendocrinology. Cell Biol. Int., 2010, 34(10), 1051-1053.
[http://dx.doi.org/10.1042/CBI20100509] [PMID: 20825365]
[64]
Vega, J.A.; García-Suárez, O.; Hannestad, J.; Pérez-Pérez, M.; Germanà, A. Neurotrophins and the immune system. J. Anat., 2003, 203(1), 1-19.
[http://dx.doi.org/10.1046/j.1469-7580.2003.00203.x] [PMID: 12892403]
[65]
Terracina, S.; Ferraguti, G.; Tarani, L.; Messina, M.P.; Lucarelli, M.; Vitali, M.; De Persis, S.; Greco, A.; Minni, A.; Polimeni, A.; Ceccanti, M.; Petrella, C.; Fiore, M. Transgenerational abnormalities induced by paternal preconceptual alcohol drinking. findings from humans and animal models. Curr. Neuropharmacol., 2022, 20(6), 1158-1173.
[http://dx.doi.org/10.2174/1570159X19666211101111430] [PMID: 34720083]
[66]
Fiore, M.; Mancinelli, R.; Aloe, L.; Laviola, G.; Sornelli, F.; Vitali, M.; Ceccanti, M. Hepatocyte growth factor, vascular endothelial growth factor, glial cell-derived neurotrophic factor and nerve growth factor are differentially affected by early chronic ethanol or red wine intake. Toxicol. Lett., 2009, 188(3), 208-213.
[http://dx.doi.org/10.1016/j.toxlet.2009.04.013] [PMID: 19397965]
[67]
Ceci, F.M.; Ferraguti, G.; Petrella, C.; Greco, A.; Ralli, M.; Iannitelli, A.; Carito, V.; Tirassa, P.; Chaldakov, G.N.; Messina, M.P.; Ceccanti, M.; Fiore, M. Nerve growth factor in alcohol use disorders. Curr. Neuropharmacol., 2021, 19(1), 45-60.
[http://dx.doi.org/10.2174/1570159X18666200429003239] [PMID: 32348226]
[68]
Ciafrè, S.; Carito, V.; Ferraguti, G.; Greco, A.; Chaldakov, G.N.G.N.; Fiore, M.; Ceccanti, M. How alcohol drinking affects our genes: An epigenetic point of view. Biochem. Cell Biol., 2019, 97(4), 345-356.
[http://dx.doi.org/10.1139/bcb-2018-0248] [PMID: 30412425]
[69]
Giagulli, V.A.; Campone, B.; Castellana, M.; Salzano, C.; Fisher, A.D.; de Angelis, C.; Pivonello, R.; Colao, A.; Pasquali, D.; Maggi, M.; Triggiani, V. Neuropsychiatric aspects in men with Klinefelter syndrome. Endocr. Metab. Immune Disord. Drug Targets, 2019, 19(2), 109-115.
[http://dx.doi.org/10.2174/1871530318666180703160250] [PMID: 29972105]
[70]
Maillefer, A.; Sabe, M.; Coste, C.; Bartolomei, J.; Jaafar, J.; Sentissi, O. Sexual identity disorder and psychosis in klinefelter syndrome: A synthesis of literature and a case report. J. Nerv. Ment. Dis., 2019, 207(2), 121-125.
[http://dx.doi.org/10.1097/NMD.0000000000000930] [PMID: 30672880]
[71]
Bojesen, A.; Juul, S.; Birkebaek, N.H.; Gravholt, C.H. Morbidity in Klinefelter syndrome: A Danish register study based on hospital discharge diagnoses. J. Clin. Endocrinol. Metab., 2006, 91(4), 1254-1260.
[http://dx.doi.org/10.1210/jc.2005-0697] [PMID: 16394093]
[72]
Gravholt, C.H.; Chang, S.; Wallentin, M.; Fedder, J.; Moore, P.; Skakkebæk, A. Klinefelter syndrome: Integrating genetics, neuropsychology, and endocrinology. Endocr. Rev., 2018, 39(4), 389-423.
[http://dx.doi.org/10.1210/er.2017-00212] [PMID: 29438472]
[73]
Salzano, A.; Arcopinto, M.; Marra, A.M.; Bobbio, E.; Esposito, D.; Accardo, G.; Giallauria, F.; Bossone, E.; Vigorito, C.; Lenzi, A.; Pasquali, D.; Isidori, A.M.; Cittadini, A. Klinefelter syndrome, cardiovascular system, and thromboembolic disease: Review of literature and clinical perspectives. Eur. J. Endocrinol., 2016, 175(1), R27-R40.
[http://dx.doi.org/10.1530/EJE-15-1025] [PMID: 26850445]
[74]
Feingold, K.R. Atypical forms of diabetes. In: Endotext; Feingold, K.R.; Anawalt, B.; Boyce, A.; Chrousos, G.; de Herder, W.W.; Dhatariya, K., Eds.; South Dartmouth, MA, 2000.
[75]
Lizarazo, A.H.; McLoughlin, M.; Vogiatzi, M.G. Endocrine aspects of Klinefelter syndrome. Curr. Opin. Endocrinol. Diabetes Obes., 2019, 26(1), 60-65.
[http://dx.doi.org/10.1097/MED.0000000000000454] [PMID: 30507702]
[76]
Petrella, C.; Di Certo, M.G.; Gabanella, F.; Barbato, C.; Ceci, F.M.; Greco, A.; Ralli, M.; Polimeni, A.; Angeloni, A.; Severini, C.; Vitali, M.; Ferraguti, G.; Ceccanti, M.; Lucarelli, M.; Severi, C.; Fiore, M. Mediterranean diet, brain and muscle: Olive polyphenols and resveratrol protection in neurodegenerative and neuromuscular disorders. Curr. Med. Chem., 2021, 28(37), 7595-7613.
[http://dx.doi.org/10.2174/0929867328666210504113445] [PMID: 33949928]
[77]
Petrella, C.; Farioli-Vecchioli, S.; Cisale, G.Y.; Strimpakos, G.; Borg, J.J.; Ceccanti, M.; Fiore, M.; Monteleone, G.; Nisticò, R. A healthy gut for a healthy brain: Preclinical, clinical and regulatory aspects. Curr. Neuropharmacol., 2021, 19(5), 610-628.
[http://dx.doi.org/10.2174/1570159X18666200730111528] [PMID: 32744976]
[78]
Chianese, R.; Coccurello, R.; Viggiano, A.; Scafuro, M.; Fiore, M.; Coppola, G.; Operto, F.F.; Fasano, S.; Laye, S.; Pierantoni, R.; Meccariello, R. Impact of dietary fats on brain functions. Curr. Neuropharmacol., 2018, 16(7), 1059-1085.
[http://dx.doi.org/10.2174/1570159X15666171017102547] [PMID: 29046155]
[79]
Jin, H.; Ji, J.J.; Zhu, Y.; Wang, X.D.; Li, Y.P.; Shi, Q.Y.; Chen, Y.F. Brain-derived neurotrophic factor, a new predictor of coronary artery calcification. Clin. Appl. Thromb., 2021, 27, 1076029621989813.
[http://dx.doi.org/10.1177/1076029621989813] [PMID: 33523719]
[80]
Skakkebæk, A.; Wallentin, M.; Gravholt, C.H. Klinefelter syndrome or testicular dysgenesis: Genetics, endocrinology, and neuropsychology. Handb. Clin. Neurol., 2021, 181, 445-462.
[http://dx.doi.org/10.1016/B978-0-12-820683-6.00032-4] [PMID: 34238477]
[81]
Zitzmann, M.; Rohayem, J. Gonadal dysfunction and beyond: Clinical challenges in children, adolescents, and adults with 47,XXY Klinefelter syndrome. Am. J. Med. Genet. C. Semin. Med. Genet., 2020, 184(2), 302-312.
[http://dx.doi.org/10.1002/ajmg.c.31786] [PMID: 32415901]
[82]
Karczewska-Kupczewska, M. Strączkowski, M.; Adamska, A.; Nikołajuk, A.; Otziomek, E.; Górska, M.; Kowalska, I. Decreased serum brain-derived neurotrophic factor concentration in young nonobese subjects with low insulin sensitivity. Clin. Biochem., 2011, 44(10-11), 817-820.
[http://dx.doi.org/10.1016/j.clinbiochem.2011.05.008] [PMID: 21620811]
[83]
Friedman, W.J.; Greene, L.A. Neurotrophin signaling via Trks and p75. Exp. Cell Res., 1999, 253(1), 131-142.
[http://dx.doi.org/10.1006/excr.1999.4705] [PMID: 10579918]
[84]
Lahita, R.G. Sex hormones and systemic lupus erythematosus. Rheum. Dis. Clin. North Am., 2000, 26(4), 951-968.
[http://dx.doi.org/10.1016/S0889-857X(05)70178-2] [PMID: 11084953]
[85]
Sawalha, A.H.; Harley, J.B.; Scofield, R.H. Autoimmunity and Klinefelter’s syndrome: When men have two X chromosomes. J. Autoimmun., 2009, 33(1), 31-34.
[http://dx.doi.org/10.1016/j.jaut.2009.03.006] [PMID: 19464849]
[86]
Swerdlow, A.J.; Higgins, C.D.; Schoemaker, M.J.; Wright, A.F.; Jacobs, P.A. Mortality in patients with Klinefelter syndrome in Britain: A cohort study. J. Clin. Endocrinol. Metab., 2005, 90(12), 6516-6522.
[http://dx.doi.org/10.1210/jc.2005-1077] [PMID: 16204366]
[87]
Swerdlow, A.J.; Schoemaker, M.J.; Higgins, C.D.; Wright, A.F.; Jacobs, P.A.; Batstone, P.J. Cancer incidence and mortality in men with Klinefelter syndrome: A cohort study. J. Natl. Cancer Inst., 2005, 97(16), 1204-1210.
[http://dx.doi.org/10.1093/jnci/dji240] [PMID: 16106025]
[88]
Tyler, C.; Edman, J.C. Down syndrome, Turner syndrome, and Klinefelter syndrome: Primary care throughout the life span. Prim. Care - Clin. Off. Pract., 2004, 31, 627-648.
[http://dx.doi.org/10.1016/j.pop.2004.04.006]
[89]
De Sanctis, V.; Fiscina, B.; Soliman, A.; Giovannini, M.; Yassin, M. Klinefelter syndrome and cancer: From childhood to adulthood. Pediatr. Endocrinol. Rev., 2013, 11(1), 44-50.
[PMID: 24079078]
[90]
Kyritsi, E.M.; Kanaka-Gantenbein, C. Autoimmune thyroid disease in specific genetic syndromes in childhood and adolescence. Front. Endocrinol. (Lausanne), 2020, 11, 543.
[http://dx.doi.org/10.3389/fendo.2020.00543] [PMID: 32973676]
[91]
Borish, L.C.; Steinke, J.W. 2. Cytokines and chemokines. J. Allergy Clin. Immunol., 2003, 111(2)(Suppl.), S460-S475.
[http://dx.doi.org/10.1067/mai.2003.108] [PMID: 12592293]
[92]
Lowry, S.F. Cytokine mediators of immunity and inflammation. Arch. Surg., 1993, 128(11), 1235-1241.
[http://dx.doi.org/10.1001/archsurg.1993.01420230063010] [PMID: 8239986]
[93]
Dhabhar, F.S. Effects of stress on immune function: The good, the bad, and the beautiful. Immunol. Res., 2014, 58(2-3), 193-210.
[http://dx.doi.org/10.1007/s12026-014-8517-0] [PMID: 24798553]
[94]
Lordan, R.; Tsoupras, A.; Zabetakis, I. Inflammation. In: The Impact of Nutrition and Statins on Cardiovascular Diseases, Academic Press; Zabetakis, I.; Lordan, R.; Tsoupras, A., Eds.; Massachussetts: Cambridge, 2019; pp. 23-51.
[http://dx.doi.org/10.1016/B978-0-12-813792-5.00002-1]
[95]
Alijotas-Reig, J.; Esteve-Valverde, E.; Ferrer-Oliveras, R.; Llurba, E.; Gris, J.M. Tumor necrosis factor-alpha and pregnancy: Focus on biologics- an updated and comprehensive review. Clin. Rev. Allergy Immunol., 2017, 53(1), 40-53.
[http://dx.doi.org/10.1007/s12016-016-8596-x] [PMID: 28054230]
[96]
Zelová, H.; Hošek, J. TNF-α signalling and inflammation: Interactions between old acquaintances. Inflamm. Res., 2013, 62(7), 641-651.
[http://dx.doi.org/10.1007/s00011-013-0633-0] [PMID: 23685857]
[97]
Kalliolias, G.D.; Ivashkiv, L.B. TNF biology, pathogenic mechanisms and emerging therapeutic strategies. Nat. Rev. Rheumatol., 2016, 12(1), 49-62.
[http://dx.doi.org/10.1038/nrrheum.2015.169] [PMID: 26656660]
[98]
Aloe, L.; Fiore, M. TNF-α expressed in the brain of transgenic mice lowers central tyroxine hydroxylase immunoreactivity and alters grooming behavior. Neurosci. Lett., 1997, 238(1-2), 65-68.
[http://dx.doi.org/10.1016/S0304-3940(97)00850-1] [PMID: 9464656]
[99]
Cimino, L.; Salemi, M.; Cannarella, R.; Condorelli, R.A.; Giurato, G.; Marchese, G.; La Vignera, S.; Calogero, A.E. Decreased miRNA expression in Klinefelter syndrome. Sci. Rep., 2017, 7(1), 16672.
[http://dx.doi.org/10.1038/s41598-017-16892-3] [PMID: 29192217]
[100]
Souyris, M.; Mejía, J.E.; Chaumeil, J.; Guéry, J.C. Female predisposition to TLR7-driven autoimmunity: Gene dosage and the escape from X chromosome inactivation. Semin. Immunopathol., 2019, 41(2), 153-164.
[http://dx.doi.org/10.1007/s00281-018-0712-y] [PMID: 30276444]
[101]
Gupta, S.; Nakabo, S.; Blanco, L.P.; O’Neil, L.J.; Wigerblad, G.; Goel, R.R.; Mistry, P.; Jiang, K.; Carmona-Rivera, C.; Chan, D.W.; Wang, X.; Pedersen, H.L.; Gadkari, M.; Howe, K.N.; Naz, F.; Dell’Orso, S.; Hasni, S.A.; Dempsey, C.; Buscetta, A.; Frischmeyer-Guerrerio, P.A.; Kruszka, P.; Muenke, M.; Franco, L.M.; Sun, H.W.; Kaplan, M.J. Sex differences in neutrophil biology modulate response to type I interferons and immunometabolism. Proc. Natl. Acad. Sci. USA, 2020, 117(28), 16481-16491.
[http://dx.doi.org/10.1073/pnas.2003603117] [PMID: 32601182]
[102]
Richard-Eaglin, A. Male and female hypogonadism. F. Nurs. Clin. North Am., 2018, 53, 395-405.
[http://dx.doi.org/10.1016/j.cnur.2018.04.006] [PMID: 30100005]
[103]
Wikström, A.M.; Dunkel, L. Klinefelter syndrome. Best Pract. Res. Clin. Endocrinol. Metab., 2011, 25(2), 239-250.
[http://dx.doi.org/10.1016/j.beem.2010.09.006] [PMID: 21397196]
[104]
Piñón, R. Biology of Human Reproduction; University Science Books: Melville, NY, 2002.
[105]
Mulhall, J.P.; Incrocci, L.; Goldstein, I.; Rosen, R. Cancer and Sexual Health; Humana: Totowa, NJ, 2011.
[http://dx.doi.org/10.1007/978-1-60761-916-1]

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