NKHANI: Phunzirani pa maphunziro omwe ali ndi vuto logonana (zachiwerewere / zachiwerewere) limafotokoza kusintha kwa epigenetic kupezeka kwa oledzera. Kusintha kwa epigenetic kunachitika m'mitundu yomwe imalumikizidwa ndi oxytocin dongosolo (lofunikira mu chikondi, kulumikizana, kukondera, kupsinjika, ndi zina zambiri). Zapamwamba:
- Zizindikiro zogonana / zolaula za epigenetic zam'magazi a oxytocin zimawoneka ngati zidakwa
- Zotsatira za kafukufuku zikugwirizana ndi Kuhn & Gallinat, 2014 (kafukufuku wotchuka wa fMRI pa ogwiritsa ntchito zolaula)
- Zomwe zapezedwa zingawonetse kusokonezeka kwakanthawi (komwe ndi kusintha kwakukulu kwa chizolowezi)
- Kusintha kwamtundu wa oxytocin kumatha kusokoneza mgwirizano, kupsinjika, magwiridwe ogonana, ndi zina zambiri.
Zambiri, werengani nkhaniyi m'malo mwaukadaulo: Asayansi amazindikira kuti mahomoni amatha kulumikizidwa ndi matenda oopsa
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Adrian E. Boström, Andreas Chatzittofis, Diana-Maria Ciuculete, John N. Flanagan, Regina Krattinger, Marcus Bandstein, Jessica Mwinyi, Gerd A. Kullak-Ublick, Katarina Görts Öberg, Stefan Arver, Helgi B. Schiöth & Jussi Jokinen (2019) )
Epigenetics, DoI: https://doi.org/10.1080/15592294.2019.1656157
Kudalirika
Hypersexual disorder (HD) idafunsidwa ngati njira yodziwira matenda mu DSM-5 ndipo gulu la 'Compulsive kugonana Behaeve Disorder' tsopano liperekedwa ngati vuto losalamulira mu ICD-11. HD imakhala ndi ziwalo zingapo zapathupi; kuphatikiza kukakamizidwa, kukakamizidwa, kukakamizidwa chilakolako chogonana komanso kuzolowera kugonana. Palibe kafukufuku wam'mbuyomu yemwe adafufuza za HD pakuwunika kwa methylation omwe amagwirizana ndi ma microRNA (miRNA) omwe amagwirizana ndi CpG. Mitundu ya genome wide methylation imayezedwa m'magazi athunthu kuchokera ku maphunziro a 60 omwe ali ndi HD ndi 33 odzipereka athanzi pogwiritsa ntchito Illumina EPIC BeadChip. 8,852 miRNA yomwe imagwirizanitsidwa ndi CpG-malo adafufuzidwa posanthula zingapo za methylation M-mtundu wodziimira payokha ngati matenda odziyimira pawokha (HD kapena odzipereka athanzi), posintha ma covariates otsimikiza kwathunthu. Ziwerengero zamagulu owonetsedwa a maRNA amafufuzidwa mwa anthu omwewo kuti athe kuwunika mayankho osiyanasiyana. Wofunsidwa methylation loci anaphunziridwanso kuti aphatikizane ndi kudalira mowa mu chipinda chodziyimira cha 107. Masamba awiri a CpG anali amalire amtundu wa HD - cg18222192 (MIR708) (p <10E-05,pFDR = 5.81E-02) ndi cg01299774 (MIR4456) (p <10E-06, pFDR = 5.81E-02). MIR4456 idatsika kwambiri kuwonetsedwa mu HD pakuwunika konse (p <0.0001) ndi kusanthula kwa multivariate (p <0.05). Cg01299774 methylation milingo idalumikizidwa mosiyana ndimafotokozedwe a MIR4456 (p <0.01) ndipo amapangidwanso mosiyanasiyana mosiyanasiyana pakudalira mowa (p = 0.026). Kuneneratu za Gene ndikuwunikira njira kuwulula kuti MIR4456 imayika ma jeni omwe amasankhidwa muubongo ndipo amatenga nawo gawo pama cell akulu am'magazi omwe amaganiza kuti ndi ofunika ku HD, mwachitsanzo, njira yodziwitsa za oxytocin. Mwachidule, kafukufuku wathu akuwonetsa zomwe MIR4456 ingapereke mu pathophysiology ya HD polimbikitsa kuwonetsa kwa oxytocin.
KUCHOKA KUGWANITSA Gawo
Mu kusanthula kwa DNA methylation m'magazi otumphukira, timazindikira masamba a CpG omwe amagwirizana ndi MIR708 ndi MIR4456 omwe ali osiyana kwambiri ndi methylated mwa odwala HD. Kuphatikiza apo, tikuwonetsa kuti hsamiR- 4456 yomwe imagwirizanitsidwa ndi methylation locus cg01299774 imasungidwa modabwitsa pakudalira kwa mowa, kuwonetsa kuti ikhoza kugwirizanitsidwa makamaka ndi chinthu chomwe chimawonetsedwa mu HD.
Pazidziwitso zathu, palibe pepala lapakale lomwe likufotokoza kufunikira kwa MIR4456 pamavuto a psychopathologies. Tikuzindikira kuti miRNA iyi imasungidwa mosinthana ndi kapangidwe kake koyambirira ndipo idaneneratu zokhazikitsidwa ndi hairpin kuyambira pomwe abwera. Kuphatikiza apo, timapereka umboni kuti mipherezero ya MRNA ya MIR4456 ikuwonetsedwa mwamalemba mu amygdala ndi hippocampus, zigawo ziwiri za ubongo zomwe Kühn et al. kukhala wophatikizidwa mu pathophysiology ya HD [5].
Kuphatikizidwa kwa njira yotsatsira oxytocin yomwe yadziwika mu phunziroli ikuwoneka kuti ili ndi chidwi kwambiri mu zambiri zomwe zimafotokozera HD monga momwe Kafka et al. [1], monga kukakamiza chilakolako chogonana, kukakamizidwa, kukakamizidwa komanso (kugonana). Makamaka opangidwa ndi paraventricular nucleus ya hypothalamus ndikumasulidwa ndi cholembera chaposachedwa, oxytocin amagwira ntchito yofunika kwambiri pakugwirizana komanso kubereka mwa amuna ndi akazi [59]. Murphy et al. adafotokoza zochuluka mokwera panthawi yogonana [60]. Burri et al. anapeza kuti ntchito ya oxytocin ya intranasal mu amuna imabweretsa kuchuluka kwa ma epinephrine plasma panthawi yogonana komanso kusintha kosintha kwa kugonana kwamkati [61]. Kuphatikiza apo, oxytocin akufuna kuti aletse zochitika za axothalamic-pituitary-adrenal (HPA) axis panthawi yamavuto. Jurek et al. adaona kuti oxytocin receptormediated intracellular methicms imalepheretsa kulembedwa kwa corticotropin-releasing factor (Crf) mu paraventricular nucleus, jini lomwe limagwirizana kwambiri ndi yankho la kupsinjika [62].
Zosintha mu njira yodziwikiratu ya oxytocin ikhoza kufotokozera zomwe zapezeka ndi Chatzittofis et al., Yemwe adawona kuwunika kwa axero kwa HPA mwa amuna omwe ali ndi vuto la hypersexual [3]. Kuphatikiza apo, kafukufuku akuwonetsa kuti oxytocin atha kukhala nawo mu pathophysiology of obsessive-activive disorder [63]. Kuyanjana kwa oxytocin ndi dopamine system, HPA-axis ndi chitetezo cha mthupi kumapangitsa kuti anthu azindikire kuti kusiyana m'magulu a oxetocin kumabweretsa chiwopsezo cha chizolowezi [64]. Ngakhale oxytocin adagwirizanapo kale ndi kayendetsedwe kazikhalidwe komanso nkhanza, Johansson et al. adawonetseranso kuti kusinthika kwa ma genetic mu oxytocin receptor gene (OXTR) kunapangitsa kuti anthu azichita zinthu mosachedwa kupsa mtima motsogozedwa ndi mowa [65]. Pomaliza, Brüne et al. adatsimikiza kuti kusinthika kwa majini ku OXTR kungathandizire kufotokozera za pathophysiology of humanline [vuto losavomerezeka], mawonekedwe amunthu omwe amadziwika kwambiri ndi kukokomeza kwakukulu [66].
MIR4456may ali ndi zowonjezera zowongolera ntchito mu HD zomwe sizinawululidwe mu kafukufuku waposachedwa. Mogwirizana ndi zomwe tapeza, kafukufuku wapitawu adanenanso za mayanjano okhudzana ndi kugonana kwa abambo ndi majini omwe amakhudzidwa ndi dongosolo la glutamatergic mwa anthu omwe ali ndi nkhawa [67]. Kuphatikiza apo, gawo la 3'-5'-cyclic adenosine mono phosphate (cAMP) paziwonetsero zogonana linawonetsedwa mumagulu achikazi, mwa kusintha phosphoprotein- 32 ndikuwongolera kusintha kwa progestin receptors [68]. Chosangalatsa ndichakuti cAMP imayang'ananso mamolekyulu omwe amagwirizanitsidwa ndi chiwongolero cha axon [69], monga gene la B3gnt1, lomwe limalumikizidwa ndi kugonana kwamtunduwu mbewa zamphongo
NKHANI YOYambirira YOPHUNZIRA:
Asayansi amazindikira kuti mahomoni amatha kulumikizidwa ndi matenda oopsa
Kafukufuku watsopano wa abambo ndi amayi omwe ali ndi vuto lotsekula wawonetsa kuthekera kwa mahomoni oxytocin, malinga ndi zotsatira zosindikizidwa mu magaziniyi Epigenetics. Kupeza kumeneku kungatsegule khomo pochiza vutoli mwa kupanga njira yoletsa ntchito yake.
Hypersexual disc, kapena kuyendetsa gawo logonana mopitirira muyeso, amadziwika kuti ndi vuto la kugonana lochita kukakamiza, lomwe limayikidwa ngati vuto loteteza anthu ku World Health Organisation. Itha kudziwidwa ndi malingaliro owonera zogonana, kukakamizidwa kuchita zachiwerewere, kulephera kudziletsa, kapena zizolowezi zogonana zomwe zimakhala ndi mavuto kapena zoopsa. Ngakhale kuchuluka kwa kuchuluka kukuyerekeza, mabuku akuwonetsa kuti vuto la hypersexual limakhudza 3-6% ya anthu.
Kutsutsana kumazungulira kuzindikiritsa chifukwa kumachitika pafupipafupi ndimatenda ena aumoyo, kutanthauza kuti akhoza kukhala kuwonjezera kapena kuwonetsa kusokonezeka kwa malingaliro komwe kulipo. Zochepa zimadziwika za neurobiology kumbuyo kwake.
"Tinayamba kufufuza njira za epigenetic zomwe zimayambitsa matenda opatsirana pogonana kuti tidziwe ngati zili ndi zizindikilo zina zomwe zimasiyanitsa ndi mavuto ena azaumoyo," akutero wolemba wamkulu Adrian Boström wochokera ku department of Neuroscience ku Uppsala University, Sweden yemwe amatsogolera phunzirani ndi ofufuza a Andrology / Sexual Medicine Group (ANOVA) ku Karolinska Institutet, Stockholm, Sweden.
"Kudziwa kwathu, kafukufuku wathuyu ndiye woyamba kupangitsa kuti ma epigenetic omwe ali ndi vuto la DNA methylation ndi ma MicroRNA azigwira komanso momwe oxytocin imagwirira ntchito muubongo mwa odwala omwe akufuna chithandizo chakuchita chiwerewere."
Asayansiwo anayeza njira za DNA methylation m'magazi kuchokera kwa odwala a 60 omwe ali ndi vuto la hypersexual ndipo anawafananizira ndi zitsanzo za odzipereka athanzi la 33.
Adasanthula zigawo za 8,852 za methylation ya DNA yokhudzana ndi ma microRNA apafupi kuti azindikire kusiyana kulikonse pakati pa zitsanzo. DNA methylation imatha kukhudza kutengera kwa majini ndi magwiridwe amtundu, momwe amathandizira kuchepetsa ntchito zawo. Komwe kusintha kwa methylation ya DNA kunapezeka, ofufuzawo adafufuza kuchuluka kwa matupi a genRNA omwe amagwirizana. Ma MicroRNA ndi osangalatsa kwambiri chifukwa amatha kudutsa chotchinga-magazi-choletsa ndikusintha kapena kufalitsa mafotokozedwe a mitundu yosiyanasiyana mazana angapo muubongo ndi ziwalo zina.
Anayerekezeranso zomwe apeza ndi zitsanzo zochokera mu maphunziro a 107, 24 a omwe anali oledzera, kufufuza kuyanjana ndi machitidwe osokoneza bongo.
Zotsatira zinazindikira zigawo ziwiri za DNA zomwe zidasinthidwa mu hypersexual disorder odwala. Ntchito yabwinobwino ya methylation ya DNA idasokonekera ndipo ma microRNA omwe amagwirizana nawo, omwe amaphatikizidwa ndi gene, atapezeka kuti sanatchulidwe. Kafukufuku adawonetsa kuti microRNA yodziwika, microRNA-4456, imatengera majini omwe nthawi zambiri amawonetsedwa kwambiri mu ubongo komanso omwe akukhudzidwa ndi kayendetsedwe ka mahomoni oxytocin. Ndi mtundu wachepetsa, mtundu wa oxytocin ungayembekezeredwe kukhala wokwezeka, ngakhale kuti kafukufuku wapano satsimikizira izi.
Zakhala zikuwoneka mu mitundu yachilengedwe komanso yamatsenga yomwe ma neuropeptide oxytocin amatenga gawo lalikulu pakukhazikitsa njira yolumikizirana. Kafukufuku wam'mbuyomu wawonetsa kuti oxytocin imagwirizanitsidwa ndi kayendetsedwe ka mgwirizano ndi anthu awiriawiri, kubereka mwakugonana komanso kuchitira nkhanza amuna ndi akazi. Kuyerekeza ndi mitu yodalira mowa kunawonetsa dera lomwelo la DNA kukhala lopanda tanthauzo, ndikuwonetsa kuti lingagwirizanidwe kwambiri ndi zomwe zimapangitsa kuti munthu azingokhala ndi vuto losokoneza bongo, monga chilolezo cha kugonana, chikhumbo chogonana, kukakamira komanso kukakamizidwa.
"Kafukufuku wowonjezera adzafunika kuti tifufuze za microRNA-4456 ndi oxytocin pamavuto a hypersexual, koma zotsatira zathu zikuwonetsa kuti kungakhale kopindulitsa kupenda phindu la mankhwala ndi psychotherapy kuti muchepetse ntchito ya oxytocin," atero Pulofesa Jussi Jokinen wochokera ku Umeå Yunivesite, Sweden.
Olembawo akuti kuchepa kwa phunziroli ndikuwonetsa kuti kusiyana kwa DNA methylation pakati pa odwala omwe ali ndi vuto lodziwika bwino komanso odzipereka omwe ali ndi thanzi labwino kunali pafupifupi 2.6%, kotero zovuta zomwe zingasinthe m'thupi zitha kukayikiridwa. Komabe, gulu lomakulirakulira laumboni lomwe lingosintha mochenjera mwa methylation limatha kukhala ndi zotsatirapo zosiyanasiyana pazikhalidwe zovuta monga kupsinjika kapena kupsinjika.
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Kafukufukuyu adalandira ndalama kudzera mu mgwirizano wam'deralo pakati pa Umeå University ndi Västerbotten County Council (ALF) komanso ndalama zomwe zimaperekedwa ndi Stockholm County Council komanso ndi Sweden Research Foundation, Åhlens Foundation, Novo Nordisk Foundation, ndi Sweden Brain Research Maziko.
NKHANI Yachiwiri YOPHUNZIRA Phunziro:
Kusintha kwa Epigenetic Kulumikizidwa ndi Hypersexual Disorder and Addictive Behaviors
Mafunso a MedicalResearch.com Ndi: Adrian E. Boström MD, m'malo mwa olemba
Dipatimenti ya Neuroscience, Uppsala University, Sweden
MedicalResearch.com: Kodi kafukufukuyu wapezeka kuti?
Yankho: Ngakhale kuchuluka kwa kuchuluka kukuyerekeza, mabuku akuwonetsa kuti hypersexual disc (HD) imakhudza anthu a 3-6%. Komabe, mkangano umazungulira kuzindikiritsa kwake ndipo ndizochepa zomwe zimadziwika za neurobiology kumbuyo kwake.
Matenda opatsirana pogonana sanafufuzidwepo kale ponena za epigenomic ndi transcriptomics munjira yophunzirira yopanda tanthauzo ndipo ndizochepa zomwe zimadziwika pokhudzana ndi neurobiology yomwe imayambitsa vutoli. Tidasanthula ngati pali kusintha kulikonse kwa epigenetic komwe kumakhudza magwiridwe antchito am'magazi a hypersexual disorder (HD) ndikuzindikira microRNA yolowetsedwa yomwe imakhulupirira kuti imathandizira magwiridwe antchito a hormone oxytocin muubongo.
Oxytocin amadziwika kuti ali ndi machitidwe osiyanasiyana. Momwe tingadziwire, palibe kafukufuku wakale yemwe adapereka umboni wothandizana pakati pa methylation ya DNA, zochita za microRNA ndi oxytocin mu vuto la hypersexual. Zomwe tapeza zikufunika kuti kafukufuku wina azitengera MIR4456 makamaka Oxytocin pamavuto a hypersexual. Maphunziro ena amafunikira kuti atsimikizire ntchito ya Oxytocin mu HD ndikuwunika ngati chithandizo chamankhwala osokoneza bongo a oxytocin chitha kukhala ndi zotsatirapo zabwino kwa odwala omwe ali ndi vuto la hypersexual.
MedicalResearch.com: Zotsatira zazikulu ndi ziti?
Yankho: - Mu phunziroli tinasanthula za 8000 yosiyanasiyana ya methylation ya DNA yokhala yopanda hypothesis komanso potero. Chifukwa chake, tidadabwitsidwa komanso kudabwa kuti tidziwe mtundu womwe umapezeka kwambiri mu ubongo ndipo umakhudzidwa ndi ma cell akuluakulu am'mitsempha yama cell omwe amaganiza kuti ndi othandiza pa vuto la hypersexual, mwachitsanzo njira ya oxytocin yosonyeza njira. Izi microRNA Zikuwonekeranso kuti chisinthiko chimasungidwa munthawi zonse, zomwe ndizopezekanso zosangalatsa komanso zosayembekezereka.
MedicalResearch.com: Kodi owerenga akuyenera kulanda chiyani ku lipoti lanu?
Yankho: Hypersexual disorder imalowetsa pathophysiological zosiyanasiyana kuphatikiza kuphatikizika, kukakamizidwa, kukakamizidwa kwa kugonana. Izi zitha kutanthauziridwa kuti vuto losokoneza bongo limakhala ndi zinthu zomwe zimawoneka ngati zosokoneza, koma siziyenera kuonedwa ngati chizolowezi. Zomwe tapezazi, poganizira za crossover yodalira mowa, zikuwonetsa kuti MIR4456 ndi njira yolembetsa oxytocin ikhoza kukhala kuti ikukhudzidwa kwambiri ndi gawo la mankhwala osokoneza bongo. Maphunziro owonjezera amafunikira kuti zitsimikizire izi.
MedicalResearch.com: Ndi malingaliro ati omwe mungakhale nawo pakufufuza kwamtsogolo chifukwa cha ntchitoyi?
Yankho: Zotsatira zathu zimalimbikitsa kafukufuku wowonjezereka wothandiza, mwachitsanzo, oxytocin wothandizila mankhwala osokoneza bongo mu vuto la hypersexual lomwe lingapangitse njira zamankhwala zatsopano kuti athetse zovuta zamankhwala omwe akukhudzidwa. Kuphatikiza apo, timazindikira mtundu wina wa MicroRNA (miRNA) womwe mtsogolo mwa miRNA yoyendetsa mankhwala omwe ukhoza kuyesedwa pamavuto a hypersexual.
MedicalResearch.com: Kodi pali china chilichonse chomwe mungafune kuwonjezera?
Yankho: DNA yathu ndi chibadwa cha majini omwe amatanthauzira mosiyanasiyana motsutsana ndi ma amino acid otchedwa mapuloteni. Mapuloteni, nawonso, amapanga gawo lalikulu lazinthu zonse zamoyo. DNA yathu ndi yobadwa ndipo siyimasintha pakapita nthawi. Kafukufukuyu, komabe, anali okhudzana ndi epigenetics, zomwe ndizosintha zomwe zimakhudza magwiridwe antchito ndi kufotokozera. Zochita za epigeneticzi zimasintha pakapita nthawi ndipo zimatha kuchepa m'matenda ena. Pali njira zosiyanasiyana za epigenetic.
Phunziroli, tidaphunzira za methylation ya DNA (njira yomwe imadziwika kuti imathandizira kusintha kwa majini, ndiye kuti kuchuluka kwa jini lomwe limamasuliridwa kukhala protein) ndi zochitika za microRNA (zigawo zazifupi zosalemba zomwe zingakhudze kutanthauzira kwa mazana angapo majini osiyanasiyana).
Poyerekeza odwala omwe ali ndi vuto la hypersexual ndi odzipereka athanzi, tidazindikira kuti DNA methylation motsatizana kuti isinthidwe kwambiri mu vuto la hypersexual. Kuti muwone kufunikira kwakupezaku, njira yomweyi ya DNA idawonetsedwanso kuti idasokonekera pamitu yodalira mowa, kuwonetsa kuti imatha kuphatikizidwa ndi zomwe zimapangitsa kuti munthu akhale ndi vuto la hypersexual. Dongosolo lodziwika bwino la DNA methylation limalumikizidwa ndi microRNA yotchedwa (microRNA 4456; MIR4456), ndikuwunikanso kuwonetsa kuti kutsata kwa methylation iyi ya DNA kumakhudza kuchuluka kwa MIR4456 komwe kumapangidwa. Kuphatikiza apo, mgulu lomweli lowerengera, tikuwonetsa kuti MIR4456 ilipo yocheperako kwambiri pamavuto a hypersexual poyerekeza ndi odzipereka athanzi, akuwonetsa mwamphamvu kuti asintha mitundu ya methylation ya DNA pamavuto a hypersexual amathandizira ndikuthandizira kufotokozera zakusokonekera kwa MIR4456. Monga microRNA: s theoretically imatha kuloza majini mazana angapo, tidagwiritsa ntchito ma kompyuta kuti tiwulule kuti MIR4456 imalunjika majini omwe amafotokozedwa bwino muubongo ndipo amatenga nawo gawo pama cell akulu am'magazi omwe amaganiza kuti ndi othandiza pa HD, mwachitsanzo, oxytocin kuwonetsa njira. Zomwe tapezazi zikufunika kuti kafukufuku wina azitengera MIR4456 makamaka Oxytocin pamavuto a hypersexual. Maphunziro ena amafunikira kuti atsimikizire ntchito ya Oxytocin mu HD ndikuwunika ngati chithandizo chamankhwala osokoneza bongo a oxytocin chitha kukhala ndi zotsatirapo zabwino kwa odwala omwe ali ndi vuto la hypersexual.
Komabe zomwe sizinasindikizidwe zomwe zimafunsidwa kuti ziwonetsetse kuwonjezeka kwakukulu kwa milingo ya Oxytocin mwa odwala omwe ali ndi vuto la hypersexual poyerekeza ndi zowongolera, komanso kuchepa kwakukulu kwa milingo ya oxytocin pambuyo pa chithandizo cha Cognitive Behaeve Therapy, kutanthauzira mwamphamvu gawo la Oxytocin mu Matenda a hypersexual ndikupangitsa kuti zomwe akunenedwa mu kafukufukuyu zikhale zolimba. Zotsatira zoyambirazi zawonetsedwa ngati cholembera chakumapeto kwa msonkhano wa Society of Biological Psychiatry mu Meyi 2019 ndikuperekanso ngati chikwangwani ku ACNP mu Disembala 2019.
Ndemanga:
Adrian E. Boström et al, Hypermethylation-based downregulation wa microRNA-4456 mu hypersexual disorder ndi chiwonetsero chodziwikiratu pakuyimira kwa oxytocin: Kusanthula kwa DNA methylation kwa mitundu ya miRNA, Epigenetics (2019). DOI: 10.1080 / 15592294.2019.1656157