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.
Kuti mudziwe zambiri, werengani nkhani yosavuta iyi: Asayansi apeza mahomoni omwe angagwirizane ndi vuto la hypersexual
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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
Matenda a Hypersexual (HD) adanenedwa ngati matenda mu DSM-5 ndipo gulu la 'Compulsive Sexual Behavior Disorder' tsopano lawonetsedwa ngati matenda oletsa kutengeka maganizo mu ICD-11. HD imaphatikizapo njira zingapo zochizira matenda; kuphatikizapo kutengeka maganizo, kukakamizidwa, kusokonezeka kwa chilakolako chogonana komanso chizolowezi chogonana. Palibe kafukufuku wakale yemwe adafufuza HD mu kusanthula kwa methylation komwe kumangokhala pa malo ogwirizana ndi CpG a microRNA (miRNA). Kapangidwe ka methylation ya genome wide kanayesedwa m'magazi athunthu kuchokera kwa anthu 60 omwe ali ndi HD ndi odzipereka 33 athanzi pogwiritsa ntchito Illumina EPIC BeadChip. Malo ogwirizana ndi CpG okwana 8,852 miRNA adafufuzidwa mu kusanthula kwa regression kwa methylation M-values ku binary independent variable of disease state (HD kapena wodzipereka wathanzi), kusintha kwa ma covariates odziwika bwino. Kuchuluka kwa ma expression a candidate miRNAs kudafufuzidwa mwa anthu omwewo kuti afufuze ma differential expression. Candidate methylation loci adaphunziridwanso kuti agwirizane ndi kudalira mowa m'gulu lodziyimira pawokha la anthu 107. Malo awiri a CpG anali ofunika kwambiri mu HD - cg18222192 (MIR708)( p < 10E-05, p FDR = 5.81E-02) ndi cg01299774 (MIR4456)(p < 10E-06, p FDR = 5.81E-02). MIR4456 inali yotsika kwambiri mu HD mu kusanthula konse kwa univariate (p < 0.0001) ndi multivariate (p < 0.05). Miyezo ya methylation ya Cg01299774 inali yogwirizana kwambiri ndi milingo yowonetsera ya MIR4456 (p < 0.01) ndipo inalinso ndi methylated mosiyana mu kudalira mowa (p = 0.026). Kuneneratu za cholinga cha majini ndi kusanthula njira za majini kunawonetsa kuti MIR4456 imalunjika majini omwe amafotokozedwa bwino muubongo ndipo omwe amagwira ntchito m'maselo akuluakulu a mitsempha omwe amaganiziridwa kuti ndi ofunikira pa HD, mwachitsanzo, njira yolumikizirana ndi oxytocin. Mwachidule, kafukufuku wathu akuwonetsa kuti MIR4456 ingathandizire pa matenda a HD mwa kukhudza kulumikizana 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 amuna ndi akazi omwe ali ndi vuto la hypersexual wavumbula kuti mwina mahomoni otchedwa oxytocin ndi omwe amagwira ntchito, malinga ndi zotsatira zomwe zafalitsidwa mu magazini ya Epigenetics . Kupeza kumeneku kungathe kutsegula chitseko chochiritsira vutoli mwa kupanga njira yoletsera 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 kuti ziwerengero za kuchuluka kwa matendawa zimasiyana, mabuku amasonyeza kuti matenda opatsirana pogonana (HD) amakhudza 3-6% ya anthu. Komabe, pali mkangano wokhudza matendawa ndipo palibe zambiri zomwe zimadziwika zokhudza matenda a mitsempha omwe ali 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 kafukufukuyu tinafufuza mitundu yoposa 8000 ya DNA methylation yomwe inakonzedwa m'njira yopanda malingaliro ndipo motero yopanda tsankho. Chifukwa chake, tinadabwa komanso kudabwa kupeza majini a microRNA omwe amawongolera kwambiri omwe amafotokozedwa makamaka muubongo ndipo omwe amagwira ntchito mu njira zazikulu zamaselo a mitsempha zomwe zimaganiziridwa kuti ndizofunikira pa vuto la hypersexual, mwachitsanzo njira yolumikizirana ya oxytocin. MicroRNA iyi ikuwonekanso kuti ndi yosungidwa mwachilengedwe m'mitundu yonse ya anyani, zomwe ndi zopeza zosangalatsa komanso zosayembekezereka.
MedicalResearch.com: Kodi owerenga akuyenera kulanda chiyani ku lipoti lanu?
Yankho: Matenda a hypersexual amaphatikizapo njira zosiyanasiyana zochizira matenda kuphatikizapo kulakalaka zinthu mopitirira muyeso, kukakamizidwa, kulephera kuchita zinthu mopitirira muyeso komanso chizolowezi chogonana. Izi zitha kutanthauziridwa motere kuti matenda a hypersexual ali ndi zinthu zosokoneza bongo, koma siziyenera kuonedwa ngati chizolowezi chokha. Zomwe tapeza, poganizira za kusinthasintha kwa kumwa mowa, zikusonyeza kuti MIR4456 ndi njira yolumikizirana ya oxytocin zitha kukhala zokhudzana kwambiri ndi chizolowezi cha matenda a hypersexual. Maphunziro ena akufunika kuti atsimikizire izi mokwanira.
MedicalResearch.com: Ndi malingaliro ati omwe mungakhale nawo pakufufuza kwamtsogolo chifukwa cha ntchitoyi?
Yankho: Zotsatira zathu zimalimbikitsa kafukufuku wowonjezereka pa momwe, mwachitsanzo, oxytocin imalamulira mankhwala ochizira matenda opatsirana pogonana omwe angathandize pa njira zatsopano zochizira kuti ziwongolere zotsatira zachipatala za omwe akhudzidwa. Kuphatikiza apo, timapeza microRNA (miRNA) inayake yomwe mankhwala oletsa matenda opatsirana pogonana omwe angayesedwe mtsogolo angayesedwe mu matenda opatsirana pogonana.
MedicalResearch.com: Kodi pali china chilichonse chomwe mungafune kuwonjezera?
Yankho: DNA yathu ndi code ya majini ya majini omwe amasandulika m'magulu osiyanasiyana a amino acid otchedwa mapuloteni. Mapuloteni, nawonso, amapanga gawo lalikulu la zamoyo zonse. DNA yathu imabadwa nayo ndipo sisintha pakapita nthawi. Komabe, kafukufukuyu anali wokhudza epigenetics, zomwe ndi kusintha komwe kumakhudza ntchito ya majini ndi mawonekedwe ake. Zochita za epigenetic izi zimasintha pakapita nthawi ndipo zimatha kusokonekera 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, Kuchepetsa kwa microRNA-4456 komwe kumakhudzana ndi Hypermethylation mu vuto la hypersexual ndi mphamvu yowonetsa pa chizindikiro cha oxytocin: Kusanthula kwa methylation ya DNA ya majini a miRNA, Epigenetics (2019). DOI: 10.1080/15592294.2019.1656157