Iinethiwekhi ze-Monoaminergic zeempawu zokuqonda kunye nokuziphatha kwisifo sikaParkinson sokuqala 

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Iimpawu zentshukumo yomzimba zezona ziphambili kwi-phenomenology kunye novavanyo lokuxilongwa kwesifo sikaParkinson (PD). Nangona kunjalo, uluhlu olubanzi lweempawu zokuziphatha nezengqondo, kubandakanya ukudakumba, ixhala, i-REM sleep behavior disorder (RBD), kunye nokuphazamiseka kwengqondo kubangela umthwalo omkhulu kubaguli. Nangona kunjalo, imvelaphi ye-neurobiological yezi mpawu zibuthathaka ezingezizo ezomzimba ayikaqondwa kakuhle.  

Kolu phononongo, sihlalutye idatha yezonyango kunye ne-[123I]FP-CIT SPECT yokufota kwezigulane ezine-PD ekuqaleni (n=349), ukulandelwa kweminyaka emi-2 (n=240)q kunye nokulandelwa kweminyaka emi-4 (n=140), kunye nolawulo olusempilweni (n=166), oluvela kwi-Parkinson's Progression Markers Initiative (PPMI) cohort. Ukudakumba, ixhala, i-RBD, kunye nokuqonda kuhlolwe kusetyenziswa imibuzo eqinisekisiweyo (GDS-15, STAI, RBDSQ kunye ne-MoCA). [123I]Idatha yokufota ye-FP-CIT SPECT ijikeleziswe kwindawo eqhelekileyo ye-MNI kusetyenziswa indlela entsha yokubhalisa engeyiyo i-linear (Niemi et al. Mov Disord 2024). Ukudibana kokubophelela kwe-[123I]FP-CIT kunye neempawu kuhlolwe i-voxel yi-voxel kuzo zonke izakhiwo ze-subcortical, kubandakanya i-striatum, i-thalamus, i-midbrain, kunye ne-brainstem. Zonke iinethiwekhi zokusebenza kwengqondo zeempawu ezithile ze-monoaminergic zidweliswe kusetyenziswa i-functional connectome (n=1000), indlela esiyibiza ngokuba yi-molecular network mapping, kwaye ii-receptor-level correspondences zazo zachazwa kusetyenziswa iimaphu ze-normative transcriptional receptor.  

Uphononongo lwethu aluzange lubonise unxulumano olubalulekileyo ekuqaleni. Ngokwecandelo, ukudakumba kwakunxulunyaniswa nokubophelela okuphantsi kwe-monoamine transporter kwi-ventral striatum (VS) emva kweminyaka emi-2 yokulandelelana nakwi-VS nakwi-dorsal raphe nucleus (DRN) emva kweminyaka emi-4 yokulandelelana, kunye nokuxhalaba kweempawu kunye nokubophelela okunciphileyo kwi-midbrain, kubandakanya i-dorsal kunye ne-median raphe nuclei kunye ne-locus coeruleus (LC), emva kweminyaka emi-4 yokulandelelana. Kuhlalutyo olude, ukubophelela okuphantsi kwesiseko kwezi ndawo kwaxela kwangaphambili ukudakumba okukhulu kunye nokuxhalaba kweempawu ekulandeleni. I-RBD ibonise umkhwa wokunxibelelana nokubophelela okunciphileyo kwi-VS kutyelelo lokulandelela lweminyaka emi-2 kunye nemi-4. Ngokwahlukileyo koko, akukho nxulumano nolwazi oluchongiweyo.  

Uhlalutyo loqhagamshelwano olusebenzayo lubonise iiprofayili zonxibelelwano ezahlukeneyo kunye nokufana nokubonakaliswa kwe-receptor kwi-monoaminergic disorders ezinxulumene nokudakumba, ixhala, kunye ne-RBD. Ii-recetor-level correspondings zabonakaliswa yi-serotonin receptors kunye ne-histamine autoreceptors yokudakumba; i-histamine, i-serotonin, kunye ne-adrenergic receptors yokudakumba; kunye ne-adrenergic kunye ne-serotonergic receptors ze-RBD. Okuphawulekayo kukuba, i-depression kunye ne-motor parkinsonism networks zifana kakhulu ne-networks ezivela kwizilonda zobuchopho ezibangela ezi mpawu, nto leyo ebonisa ukuba i-monoaminergic networks echongiweyo inokuba nefuthe elibalulekileyo.  

Iziphumo zophando lwethu zibonisa ukungaqheleki kwe-monoaminergic kunye neeprofayili zazo zonxibelelwano ezinxulumene neempawu ezininzi ezingezizo iimoto kwi-PD. Ukungabikho kokunxibelelana nokuqonda kuhambelana kakhulu nesiseko se-cholinergic endaweni ye-monoaminergic sokungasebenzi kakuhle kwengqondo kwi-PD, nangona inani elincinci lezigulana ezikhubazekileyo kwengqondo kweli qela le-PD yokuqala linciphisa amandla. Imvelaphi yeempawu isenokuba yeyamaqela amaninzi, ibandakanya utshintsho oluphambili nolwesibini kwiinkqubo ezininzi ze-neurotransmitter. Zizonke, ezi ziphumo ziqhubela phambili ukuqonda kwethu iindlela ze-neurobiological eziphantsi kwe-spectrum yeempawu ezingezizo iimoto ze-PD.

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