Ho netefatsa mohlala oa ts'ebetso ea motlakase bakeng sa bana ba nang le cerebral palsy.
Nts'etsopele ea mohlala oa ts'ebetso ea likoloi ho bana ba nang le cerebral palsy (CP) ha e so ngoloe. Sepheo sa phuputso ena e ne e le ho hlahloba mohlala oa ts'ebetso ea motlakase ho bana ba nang le CP le ho sebelisa mohlala ho aha li-curve tse kholo tsa motlakase bakeng sa mohato o mong le o mong oa 5 oa Gross Motor Function Classification System (GMFCS). Mohlala oa stratified oa bana ba 586 ba nang le CP, 1 ho ea ho lilemo tse 12, ba lulang Ontario, Canada, 'me ba tsebahala ka litsi tsa tsosoloso ba ile ba kenya letsoho. Lithuto li ile tsa aroloa ho sebelisoa GMFCS, 'me mohlala oa ts'ebetso ea motlakase o lekantsoe ka Gross Motor Function Measure (GMFM). Mefuta e mene e ile ea hlahlojoa ho etsa li-curve tse hlalosang kamano e sa lekanyetsoang pakeng tsa lilemo le mohlala oa mosebetsi oa motlakase. Mohlala oo ka bobeli moeli oa moeli (boholo ba lintlha tsa GMFM) le tekanyo ea tekanyo (sekhahla seo palo e kholo ea GMFM e atamelang) e fapaneng bakeng sa boemo bo bong le bo bong ba GMFCS bo hlalositseng 83% ea phapang ea lintlha tsa GMFM.
Boloetse ba Huntington (HD) bo bakoa ke keketseho e sa tloaelehang ea ho pheta-pheta CAG ho gene encoding huntingtin. Nts'etsopele ea liphekolo tsa HD e hloka tlhahlobo ea pele ea litlhare mefuteng ea liphoofolo tse hlahisang ho se sebetse hantle le mafu a tikoloho a bonoang ho HD. Re hlahisitse mofuta o mocha oa motlakase oa HD o nang le mouse ea chimeric / human exon 1 e nang le 140 CAG e pheta-pheta e kentsoeng mofuteng oa ho tsoma oa murine. Litoeba tsena li bonts'itse ts'ebetso e ntseng e eketseha ea li-locomotor le ho holisa ha li le khoeling ea 1, li lateloa ke hypoactivity likhoeling tsa 4 le mathata a ho tsamaea ha selemo sa 1. Matšoao a boitšoaro a ile a etella pele ho senyeha ha neuropathological, e ileng ea e-ba matla le ho ata feela ha a le likhoeli tse 4. Tsena li ne li e-na le litšila tsa nyutlelie bakeng sa ho tsoma le ho tsoma tse nang le nyutlelie le li-neuropil aggregates tse qalileng ho hlaha ka har'a striatum, nucleus accumbens, le tubercle ea monko. Ho khahlisang, libaka tse nang le mafu a pele kaofela li fumana likenyelletso tse teteaneng tsa dopaminergic, tse tšehetsang bopaki bo bokelletsoeng ba karolo ea dopamine ho lefu la HD.
Lintlha tse hlophisitsoeng tsa maqhubu li tlalehoa bakeng sa liluma-nosi tsa Seswedishe tse hlahisitsoeng ka bobeli ka mandible e tsitsitseng le e sa tsitsang. Ho ile ha etsoa litekanyo nakong ea pele ea glottal pulse ho lekanyetsa tlhaloso ea liphetho mecheng ea maikutlo e sa utloahaleng. Liphetho li bonts'itse hore leha ho ne ho bulehile mehlahare eo e seng ea tlhaho, barupeluoa ba khonne ho hlahisa lipaterone tsa F ka har'a mefuta e fapaneng ea liluma-nosi tse tloaelehileng. Liphetho li hlalositsoe ka ho nahana hore "ho ithuta hang-hang" ka mesebetsi e sa tloaelehang haholo, joalo ka ho hlakisa liluma-nosi tse sa fetoheng, hoa khoneha hobane lenaneo le tloaelehileng la motors ea puo ke "tefello" ho fapana le hore libui li ipapisitse le boiphihlelo ba nakong e fetileng kapa ho kopa mohlala o ikgethang wa metjhine ya enjine e fapaneng le ya puo ya tlhaho. Ke hore, e sebetsa ka mokhoa o nahanelang maemo ho fihlela sepheo se lebisitsoeng ho bamameli. Kaha "litaba" li etsa sehlopha sa liketsahalo tse sa feleng, lenaneo le tlameha ho ba "boqapi," kapa le khona ho sebetsana le maemo a neng a e-so ka a ba teng pele.
Boithuto ba hajoale bo fana ka mohlala o ka hlahisoang hape oa ho senyeha ha liteko tsa mofuta oa li-motor neurons ho rat. Ho tsukutleha ha metso ea ventral ho motho e moholo oa lumbar cord transects ea mohlala oa li-axon tsa motlakase motsong oa ho tsoa 'me ho lebisa ho lefu la lisele tsa morao-rao tsa 80% ea mohlala oa li-motor neurons libeke tse 2 hamorao; sephetho sena se latela letoto la liphetoho tsa morao-rao, ho kenyelletsa chromatolysis, tahlehelo ea phenotype e fetisang, le ho bokellana ha phosphorylated neurofilaments ho perikarya. Lisele tsa Glial tse ngolisitsoeng sebakeng sa kotsi ea morao li hlahisa li-epitopes tse khethehileng tsa microglia (joalokaha ho bontšitsoe ke OX-42 immunoreactivity) le matšoao a khethehileng a macrophage (mohlala, ED-1 immunoreactivity). Matšoao a khethehileng a macrophage a ba matla haholo matsatsi a 7 a postaxotomy mme a fana ka bopaki bo eketsehileng ba phagocytosis e sebetsang ea li-neurone tse lemetseng. Ventral root avulsion ke mohlala o molemo haholo bakeng sa ho hlahloba mekhoa ea lefu la motor neuron le ho hlahloba bokhoni ba trophic factor le mahlahana a mang ho boloka phenotype le ho khothalletsa ba phelang.
Bopaki bo bongata bo bontšitse hore cerebellum e phetha karolo ea bohlokoa molokong oa metsamao. Karolo ea bohlokoa ea tlhahiso ea enjene ke nako ea eona mabapi le ts'usumetso ea kantle kapa likarolo tse ling tsa motsamao. Liphuputso tse fetileng li fana ka maikutlo a hore cerebellum e bapala karolo ea nako ea ho sisinyeha. Mona re hlalosa mohlala oa marang-rang oa neural o thehiloeng ho mokhatlo oa synaptic oa cerebellum o ka hlahisang likarabo tsa nako ka har'a mashome a li-milliseconds ho isa metsotsoana. Ho fapana le mefuta e fetileng, likhoutu tsa nakoana li hlaha ho matla a potoloho ea cerebellar 'me ha li itšetlehe ka tieho ea conduction, lihlopha tsa likarolo tse nang le linako tse sa fetoheng, kapa palo ea likarolo tse tsamaeang ka maqhubu a fapaneng. Ho e-na le hoo, nako e ntšoa ho tsoa ho vector ea hang-hang ea granule cell. Karolo e ka tlase ea lisele tse sebetsang tsa granule e fapana ka nako ka lebaka la maikutlo a fosahetseng a granule-Golgi-granule cell.
Spinal muscular atrophy (SMA) e bakoa ke phetoho ea homozygous kapa ho hlakoloa ha SMN1 gene encoding pholoha protheine ea motor neuron (SMN), e bakang tahlehelo e ikhethileng ea li-alpha-motor neurons. Batho hangata ba na le kopi e le 'ngoe kapa ho feta tsa mofuta oa SMN2, sebaka sa likhoutu se batlang se ts'oana le SMN1, ntle le hore phetoho ea ntlha e baka ho arohana ho tsoa ho exon 7 le tlhahiso ea protheine ea SMNDelta7 e sa sebetseng haholo. Nts'etsopele ea lithethefatsi tse fokotsang ho arohana ha SMN2 ke mokhoa o khahlang oa kalafo bakeng sa SMA. Haufinyane tjena ho entsoe steric block antisense oligonucleotide (AO) e ileng ea thibela intronic splice suppressor element, le ho ntlafatsa SMN2 exon 7 kenyeletso ho SMA mokuli fibroblasts. Mona, re bonts'a hore phano ea nako ea intracerebroventricular (ICV) ea AO ena e ile ea fella ka ho eketseha ha polelo ea SMN bokong le lesapong la mokokotlo ho fihlela ho 50% ea boemo ba littermate tse phetseng hantle. PCR ea nako ea sebele ea lingoliloeng tsa SMN2 e netefalitse keketseho ea AO-mediated ho SMN ea bolelele bo felletseng.
Ho ile ha hahuoa mohlala o lekanyelitsoeng oa nako le litokiso tsa liphoso o ikemiselitseng ho hlalosa mekhoa e tsamaisanang le mosebetsi oa thuto ka paradigm ea liteko, eo ho eona mosebetsi e leng ho hokahanya tatellano ea liketso tsa motlakase ho latela tatellano ea lintho tse susumetsang. Mohlala o na le mekhoa e 'meli ea ho lokisa liphoso: (1) litokiso tsa nako (maqhubu a inverted) a tatellano ea likarabo; (2) litokiso tsa phetoho ea mohato oa tatellano eo (phoso ea ho hokahanya). Leqepheng lena, ho hlahlojoa tšusumetso ea mefuta e fapaneng ea mekhoa e nepahetseng ea physiologically le ea maemo a pele ka tatellano ea karabo e tsitsitseng hammoho le botsitso ba ts'ebetso ea mohlala. Mohlala o tsitsitse bakeng sa phaello ea ho lokisa liphoso ho tloha ho 0 ho ea ho 2. Ho bapisoa le boitsebiso bo tsebahalang ba empirical bo tšehetsa maikutlo a hore litekanyetso tse utloahalang li ka tlaase ho 1. Ho feta moo, ho hlahisoa mokhoa o mong oa mokhoa oa motheo oa linear moo ho ka khonehang sebopeho sa ho buisanoa ka mokhoa oa ho fumana boikemelo ba phoso ea ho hokahanya.
Ho hlahisoa mofuta oa nako o koetsoeng o ikarabellang bakeng sa liketsahalo tse 'maloa tse hlokometsoeng mesebetsing e hlokang tlhahiso ea tatellano ea liketso tsa makoloi ka tumellano le tatellano ea tšusumetso. Ho fapana le mehlala e fetileng, mefuta e mengata e fumanehang tsamaisong ea methapo e bohareng ea taba (mefuta e ka hare) le mefuta e ka lekanngoang ka ntle e khetholloa, 'me ho kenyelelitsoe mefuta e mengata ea ka hare ea physiologically justifiable. Mohlala o nka boteng ba (a) mohlokomeli oa nako ea ka hare ea hlahisang nako ea litšupiso e sebelisoang karolong ea ho laola motlakase bakeng sa nako ea taelo e latelang ea motlakase; (b) synchrony ea ka hare (subjective) e itšetlehileng ka lintlha tse ling tsa morao-rao (tlhaloso) mabapi le qalo e seng e entsoe ea ketso ea motlakase. Ho na le mekhoa e 'meli ea ho lokisa liphoso: (1) nako (inverted frequency) - nako ea litšupiso (nako) e behiloe qalong ea mosebetsi ho latela nako ea ho qala ha interstimulus-ho qala (s) mme hamorao e lokisoa bakeng sa ho fapana. .
Lisebelisoa tsa mafura ke mehlala ea liqeto (lihlahisoa tsa software) tse ntseng li nkoa e le lisebelisoa tse sebetsang tsa taolo ea mafura ke bajari ba literaka ba US. Ka ho sebelisa lintlha tsa morao-rao tsa litheko tsa sebaka se seng le se seng sa literaka, mefuta ena e lekanya lenane le nepahetseng la mafura bakeng sa tsela e 'ngoe le e 'ngoe e bontšang: (i) hore na ho tla sebelisoa liema-teraka life, le (ii) hore na u ka reka mafura a makae sebakeng se khethiloeng s) ho fokotsa litšenyehelo tsa ho tlatsa mafura. Leha ho le joalo, ka mokhoa oa hona joale, mefuta ena e fokotsa litšenyehelo tsa mafura feela, 'me e hlokomoloha kapa e nyenyefatsa litšenyehelo tse ling tse angoang ke liqeto tse fapaneng tsa mehlala. Ho latela lipuisano le baokameli ba lipalangoang, bakhanni ba literaka, le barekisi ba lisebelisoa tsa peterole, sengoloa sena se sisinya mokhoa o felletseng oa ho ntlafatsa mafura a sepalangoang o nahanang ka litšenyehelo tsohle tse angoang ke khetho ea mofuta ona. Liphetho tsa papiso li fana ka maikutlo a hore mofuta o reriloeng ha o fihlelle feela litšenyehelo tse tlase tsa ts'ebetso ea koloi ho feta lisebelisoa tsa mafura a khoebo, empa hape o fana ka litharollo tse lakatsehang ho latela pono ea bakhanni.
Ho kenngoa ha intraspinal ea lisele tsa methapo ea methapo ea motho ho emela mokhoa o tšepisang oa ho khothalletsa ho hlaphoheloa ha mosebetsi ka mor'a ts'oaetso ea mokokotlo. Kalafo e joalo e ka sebetsa ho: I) ho fana ka ts'ehetso ea trophic ho ntlafatsa bophelo ba li-neurone tse amohelang; II) ho ntlafatsa botšepehi ba sebopeho sa parenchyma ea lesapo la mokokotlo ka ho fokotsa syringomyelia le leqeba libakeng tse lemetseng ho sithabela maikutlo; le III) li fana ka li-neuronal populations hore li ka etsa li-relay tse nang le li-axon tse amohelang batho, li-interneurons tsa segmental, le/kapa α-motoneurons. Mona re bonts'itse phello ea ho hlomathiseletsoa ka har'a mokokotlo oa sehlopha sa kliniki sa "fetal spinal cord-derived neural stem cells" (HSSC) mabapi le ho hlaphoheloa ha methapo ea kutlo ka mokhoa oa rat oa kotsi ea khatello ea lumbar (L3). Likhoto tse tšehali tse likhoeli li tharo tsa Sprague–Dawley li ile tsa fumana leqeba la khatello ea lesapo la mokokotlo la L3. Matsatsi a mararo ka mor'a kotsi, liphoofolo li ile tsa etsoa ka mokhoa o sa tloaelehang 'me tsa fumana liente tsa intraspinal tsa HSSC, mecha ea litaba feela, kapa ha ho liente. Liphoofolo tsohle li ne li e-na le immunosuppressed ka tacrolimus, mycophenolate mofetil, le methylprednisolone acetate ho tloha letsatsing la cell grafting 'me li pholohile libeke tse robeli.
Re bontšitse pejana hore tsamaiso ea quercetin ka mor'a kotsi ea mokokotlo ka mokhoa oa rat e ile ea etsa hore ho hlaphoheloe ho hoholo ha mosebetsi oa motlakase. Mohlala o ts'oanang oa lesapo la mokokotlo oa lesapo la mokokotlo, re se re hokahanya nako ea kalafo le tekanyo eo ts'ebetso ea motlakase e fumanoang. MEKHOA: Likhoto tse mashome a supileng a metso e mene tsa Wistar li ile tsa abeloa lihlopha tse robeli tsa liteko. Kotsi ea mokokotlo ea bohareng ba thoracic e ile ea hlahisoa liphoofolong tsa lihlopha tse supileng. Quercetin e ne e tsamaisoa ka intraperitoneally ka tekanyo ea motho ka mong ea 25 micromol kg (-1). Kalafo e qalile hora e 1 ka mor'a kotsi. Bolelele ba kalafo bo tloha ho ente e le 'ngoe ho isa matsatsing a 10, ka makhetlo a mabeli kapa a mararo ka letsatsi. Ho ile ha fumanoa lintlha tsa BBB (Basso, Beattie le Bresnahan) 'me ho bolokoa ha lisele sebakeng sa kotsi ho ile ha hlahlojoa. LITLHAKISO: Ha ho le e 'ngoe ea liphoofolo tse sa laoleheng tse ileng tsa fumana tšebetso ea motlakase e lekaneng ho tsamaea. Ha quercetin e ne e sebelisoa habeli ka letsatsi ka nako ea matsatsi a 3 kapa a 10, hoo e ka bang karolo ea 50 lekholong ea liphoofolo e ile ea fumana tšebetso e lekaneng ea ho tsamaea.
Tlhahlobo e tsitsitseng e etsoa ka mokhoa oa kinetic bakeng sa phetoho e rarahaneng ea koloi ea flagellar ea Halobacterium salinarum (Nutsch et al. [16]). Ho ba teng le ho ikhethang ha boemo bo botle bo tsitsitseng ba tsamaiso bo thehiloe 'me ho bontšoa hore na ke hobane'ng ha boemo bo tsitsitseng bo tsepamisitsoe ho pota-pota mohato o nang le bokhoni, boemo ba motlakase oo ho oona o khonang ho arabela ho ts'oaetso ea leseli. Ho boetse ho bontšoa hore na ke hobane'ng ha boemo bo tsitsitseng bo fetohela mohatong oa refractory ha boleng ba boemo bo tsitsitseng ba CheYP bo laolang likarabo bo ntse bo eketseha. Mosebetsi ona ke karolo e 'ngoe ea ho etsa mohlala ho baeloji ea litsamaiso moo ho thehoang litšobotsi tsa lipalo tsa mohlala.
Letoto le felletseng la mabaka a bakang ho Amyotrophic lateral sclerosis (ALS) le ntse le le thata, empa khatello ea oxidative e nkoa e le eona e tlatsetsang. Liphetoho ho Cu/Zn superoxide dismutase 1 (SOD-1), e amanang le ALS ea lelapa, e khothalletsa tšenyo e atileng ea oxidative. Litoeba tse buang ka litoeba tsa G93A tse fetotseng motho SOD-1 li bonts'a liphetoho tse ngata tsa mafu a ALS 'me ka hona li na le thuso bakeng sa nts'etsopele ea kalafo. Tlatsetso ea lijo ka S-adenosyl methionine (SAM) e fane ka litlamorao tse ngata tsa neuroprotective mefuteng ea litoeba tsa lefu la kelello le amanang le lilemo. Re ile ra hlahloba mona hore na tlatsetso ea SAM e ka ama tsela ea motor neuron pathology ho litoeba tse hlalosang phetoho ea motho SOD-SAM e liehisa lefu le qalang libeke tsa 2-3. SAM e boetse e liehile matšoao a neurodegeneration ho litoeba tsena le ho ALS, ho kenyelletsa ho thibela tahlehelo ea methapo ea kutlo, le ho fokotsa gliosis, aggregation ea SOD-1, protheine.
Litlhahlobo tsa Electromyographical tsa tahlehelo ea yuniti ea makoloi pele ho matšoao ho mofuta oa SOD1 transgenic mouse oa amyotrophic lateral sclerosis (ALS) li hlahisitse liphetho tse hanyetsanang mabapi le ho qala le nako. Re rekotile matla a isometric a mesifa ea morao-rao le ea motor unit ho fumana nomoro ea yuniti ea koloi le boholo ba nako eohle ea bophelo ba litoeba. Linomoro tsa motlakase ka lebelo la tibialis anterior, extensor digitorum longus le medial gastrocnemius mesifa li fokotsehile ho tloha matsatsing a 40, matsatsi a 50 pele ho tlalehoa matšoao a mangata le tahlehelo ea motoneuron. Linomoro tsa motlakase li ile tsa theoha ka mor'a matšoao a hlakileng a mesifa ea soleus e tsamaeang butle. Matla a mesifa a fokotsehile ka ho bapa le linomoro tsa motlakase, ho bonts'a puseletso e fokolang kapa e sa sebetseng ka ho mela. Ho fokotseha ho hoholo ha mesifa ho bile teng ka lebaka la ho ba kotsing e ikhethileng ea li-unit tsa makoloi tse kholo, tse potlakileng, tse kentsoeng ke li-motoneurons tse kholo. Ka hona li-motoneuron tse kholo ke tsona tse tlokotsing ka ho fetesisa ho ALS ka lefu la mokokotlo le hlahang pele ho matšoao a hlakileng. Re fihlela qeto ea hore boholo ba li-motoneuron, li-axon tsa tsona le boholo ba yuniti ea tsona li bohlokoa.
Ho hloleha ha moroto ke boemo bo fokolisang bo amang batho ba baholo haholo. Mokhoa o mong o ka sehloohong o bakoa ke ho koaleha ho sa feleng ha striated urethral sphincter e amanang le fibrosis. Bangoli ba ile ba batlisisa qetello ea lisele tsa pele tsa mesifa (MPC) tse kenngoeng ka mohlala oa kotsi ea striated urethral sphincter e hlahisang liphetoho tsa histopathologic tsa sphincter insufficiency. The striated urethral sphincter ea likhoto tse tona tse tsofetseng e sentsoe ke electrocoagulation. Li-MPC li ne li arohane le li-explant tsa myofiber, tse tšoaelitsoeng ke adenovirus e jereng transgene encoding beta-galactosidase, 'me e kenngoa ka har'a sphincter ea phoofolo e tšoanang matsatsi a 37 ka mor'a kotsi. Liphoofolo li ile tsa bolaoa matsatsi a 5 le a 30 ka mor'a ente bakeng sa tlhahlobo ea ts'ebetso ea sphincter le ho thehoa ha likarolo tsa motlakase. Electrocoagulation e ile ea fella ka timetso e ke keng ea qojoa ea li-myofiber tse peli tsa sphincteric le methapo ea methapo, ka ho se sebetse hantle ha sphincter e senyehileng ho boloka keketseho ea khatello ea senya; atrophy le fibrosis li hlaha kamora khoeli e le 'ngoe.
The childhood motor neuron disease spinal muscular atrophy (SMA) e bakoa ke ho fokotseha ha polelo ea gene ea survival motor neuron (SMN). Lithuto tse fetileng tse sebelisang li-in vitro model system le lintho tse phelang tse tlase li bontšitse hore maemo a tlase a protheine ea Smn a sitisa nts'etsopele ea bakhachane ka har'a li-neurone tse tlase, tse susumetsang kholo ea methapo ea kutlo, axon branching le neuromuscular connection. Tekanyo eo litsela tsena tsa nts'etsopele li kenyang letsoho ho ba kotsing e ikhethileng le pathology tsamaisong ea mammalian neuromuscular in vivo e ntse e sa hlaka. Mona, re entse lipatlisiso ka nts'etsopele ea matšoao a khokahano ea methapo ea kutlo ho batho ba kotsing e fapaneng ea motor neuron ho Smn(-/-); SMN2 litoeba, mohlala oa SMA e matla. Re bonts'a hore maemo a Smn a fokotsehileng ha a na phello e bonoang ho li-morphological correlates tsa nts'etsopele ea pele ho matšoao ho li-motor units tse kotsing kapa tse tsitsitseng, e leng se bontšang hore mekhoa e sa tloaelehang ea tsoelo-pele ea pele ho matšoao e ke ke ea e-ba ntho e hlokahalang bakeng sa liphetoho tse latelang tsa pathological.
Khopolo-taba e ka sehloohong ea thuto ena e ne e le hore mokhoa oa motlakase oa khohlela o hlahisoa, bonyane ka karolo e 'ngoe, ke marang-rang a medullary breathing neuronal ho arabela ho tsoa ho "khohlela" le pulmonary stretch receptor relay neurons nucleus tractus solitarii. Lipapiso tsa khomphutha tsa mofuta oa marang-rang o phatlalalitsoeng o nang le likhokahano tse reriloeng ho tloha ho nucleus tractus solitarii ho isa ho ventrolateral medullary breathing neurons li hlahisitse mekhoa ea makoloi a khohlela le a expiratory. Likarabo tse boletsoeng esale pele tsa "mefuta" e fapaneng ea li-neurone (I-DRIVER, I-AUG, I-DEC, E-AUG, le E-DEC) tse tsoang lipapisong li ile tsa lekoa ka vivo. Likarabo tse tšoanang le tse latellanang tsa li-neurone tse nang le ts'ebetso ea phefumoloho li ile tsa shejoa nakong ea khohlela ea tlhaho ho likatse tse holofetseng, tse shoeleng litho, le tse nang le moea. Mekhoa e kang ea khohlela methapong ea phrenic le lumbar e ile ea hlahisoa ke ts'ebetso ea mechine ea trachea ea intrathoracic. Mekhoa e fetotsoeng ea ho ntša metsi e ile ea lekanyetsoa mefuteng e mengata ea li-neuron tsa phefumoloho nakong ea khohlela ea tlhaho.
The autosomal recessive mutation mnd2 e fella ka lefu le qalang la motor neuron le ho holofala ho tsoelang pele ka potlako, ho senyeha ho matla ha mesifa, ho theoha ha thymus le spleen, le lefu pele ho matsatsi a 40. mnd2 e entsoe 'mapa oa chromosome ea 6 ka mofuta oa mofuta: centromere-Tcrb-Ly-2-Sftp-3-D6Mit4-mnd2-D6Mit6, D6Mit9-D6Rck132-Raf-1, D6Mit11-D6Mit12-D6Mit14. mnd2 e fumaneha ka har'a sehlopha sa khokahano se bolokiloeng se nang le li-homolog ho chromosome ea motho 2p12-p13. Li-neuron tsa mokokotlo oa liphoofolo tse anngoeng ke li-homozygous lia ruruha 'me li na le letheba le fokolang,' me electromyography e senola ts'ebetso e iketsahallang feela ea ho fokola ha mesifa. Myelin staining e ne e tloaelehile ho pholletsa le neuraxis. Maikutlo a tleliniki a tsamaisana le ho se tloaelehe ha tšebetso ea methapo ea kutlo e tlase. Moetso ona o mocha oa liphoofolo o tla ba oa bohlokoa bakeng sa ho tsebahatsa bofokoli ba lefutso bo ikarabellang bakeng sa lefu la motor neuron le tlhahlobo ea liphekolo tse ncha.
Lefu la Parkinson (PD) ke lefu le tloaelehileng la neurodegenerative le bonts'ang ho se sebetse ha likoloi, joalo ka ho thothomela, akinesia le ho tiea. Thutong ea hona joale, re entse lipatlisiso tsa hore na tlhahlobo ea ho sesa e ka sebelisoa e le e 'ngoe ea mekhoa ea ho hlahloba boitšoaro ho ithuta bokooa ba koloi ho 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) -induced parkinsonism. mefuta e 'meli ea litoeba, Balb/c le C57BL/6. Litoeba li ne li phekoloa ka litekanyetso tse fapaneng tsa MPTP (10, 20 le 30 mg / kg, habeli, 16 h ka thōko), 'me li ile tsa etsoa tlhahlobo ea ho sesa ka letsatsi la boraro la ente ea pele ea MPTP. Ho thothomela ho bakoang ke MPTP ho ile ha behoa leihlo ka metsotso e 30, 'me akinesia le ho tiea ho ile ha ithutoa lihora tse 3 ka mor'a phekolo ea bobeli ea MPTP. Le hoja ho thothomela le akinesia tse hlahisitsoeng li ne li itšetlehile ka tekanyo ea litekanyetso 'me matla a ho thothomela a bapisoa le mefuta e' meli ea litoeba tse ithutoang, karabo ea ho qetela ho C57BL/6 e ne e le tlase haholo ho feta e bonoang Balb/c. Regidity e bontšitsoeng ho Balb / c litoeba e ne e itšetlehile ka tekanyo, empa eseng ho C57BL/6.
Bopaki bo fapaneng bo fana ka maikutlo a hore amyotrophic lateral sclerosis (ALS) e ama ka mokhoa o ikhethileng tšebetso ea methapo ea kutlo, empa liphetoho tsa electrophysiological tsa methapo ea kutlo e le 'ngoe ho ALS e sa ntse e tla ngoloa. Mosebetsing oa hona joale, thabo ea li-motor neurons e lekiloe ka mokhoa oa toeba oa transgenic oa mofuta oa lelapa oa ALS, o amanang le phetoho ea Cu, Zn superoxide dismutase (Gly 93 → Ala). Lirekoto tsa li-patch-clamp tsa bokhoni ba membrane ho li-transgenic motor neurons li bonts'itse hore li tuka ka makhetlo a mangata le nako e khuts'oane ha li bapisoa le li-motor neurons tse tsoang ho litoeba tsa taolo. Leha ho le joalo, li-membrane tse sa sebetseng tsa li-neurone tsena li ne li lekana. Liphetho tse joalo li fana ka maikutlo a hore thabo e fetotsoeng ea motor neuron e tsamaisana le phetoho e amanang le ALS mme e ka tlatsetsang ho pathogenesis ea lefu lena.
Kalafo ya ho busetsa disele ho phatlaladitswe ka bophara e le pheko ya mafu a mangata ho kenyeletswa lefu la motor neuron. Lisele tse fapaneng tsa bafani li 'nile tsa lekoa bakeng sa phekolo ho kenyeletsa litokisetso tse ka thōko ho tloha mokong oa masapo le mokokotlo oa mokokotlo oa embryonic. Mohloli o mong oa lisele, lisele tsa Sertoli, li 'nile tsa sebelisoa ka katleho mefuteng ea lefu la tsoekere, lefu la Parkinson le lefu la Huntington. Bokhoni ba lisele tsena tsa ho hlahisa liprotheine tsa cytoprotective le karolo ea tsona joalo ka 'lisele tsa baoki' tse ts'ehetsang ts'ebetso ea mefuta e meng ea lisele ka har'a testes li fana ka maikutlo a ts'ebeliso ea tsona joalo ka lisele tsa neuroprotective. Phuputso ea morao-rao e hlahloba bokhoni ba lisele tsa Sertoli tse kenngoeng ka har'a parenchyma ea lesapo la mokokotlo ho sireletsa methapo ea motlakase ka mokhoa oa mouse bakeng sa amyotrophic lateral sclerosis. Litoeba tse mashome a supileng tsa transgenic tse hlalosang phetoho (G93A) ea motho Cu-Zn superoxide dismutase (SOD1) e fumane ente e le 'ngoe ea mokokotlo oa lisele tsa testicular tse entsoeng ka Sertoli ka har'a lenaka la L4-L5 ventral (kakaretso ea lisele tsa 1 × 105) pele ho qala matšoao a kliniki. .
Mofuta o mocha oa baktheria oa maiketsetso oa chromosome transgenic mouse (BACHD) o hlahisa likarolo tsa phenotypic tsa HD ho kenyeletsoa haholo-holo ho kopana ha liprotheine tse amanang le neuropil le ho se sebetse hantle ha 'mele ka mokhoa o ikhethileng oa lefu la neurodegenerative. Ho se sebetse ha likoloi ho bontšitsoe ho etella pele neuropathology ho litoeba tsa BACHD. Ka hona re ile ra batlisisa tsoelo-pele ea synaptic pathology liseleng tsa pyramidal le interneurons tsa superficial motor cortex ea BACHD litoeba. Ho ile ha etsoa lirekoto tsa "whole-cell patch clamp" liseleng tsa 2/3 tsa mantlha tsa cortical pyramidal le li-interneurons tsa parvalbumin tse tsoang ho litoeba tsa BACHD likhoeling tsa 3, ha litoeba li qala ho bontša ho se sebetse hantle ha koloi, 'me likhoeling tse 6, ha ho se sebetse ho matla ho matla le ho feta. .
The motor neuron degeneration mutation (Mnd) e baka ho qala morao-rao, ho senyeha ho tsoelang pele ha li-neuron tse ka holimo le tse tlaase ho litoeba. Kamora ho theha maemo a liphatsa tsa lefutso le tikoloho a khethollang phenotypes ea Mnd/Mnd ho tloha +/ Mnd litoeba, Mnd e ile ea etsoa 'mapa ho ea ho proximal Chr 8, ho sebelisoa li-retroviruses tse sa feleng joalo ka matšoao. Sebaka sa 'mapa se netefalitsoe ka matšoao a eketsehileng a amanang le polymorphic. Li-outcross / intercross matings ho mofuta oa AKR/J, tse neng li sebelisetsoa ho latela karohano ea matšoao a retroviral mabapi le Mnd, le tsona li senotse ho ba teng ha phello ea nako. Hoo e ka bang karolo e le 'ngoe ho tse 'nè ea bana ba Mnd/Mnd F2 ba amehileng ba bontšitse lefu le potlakileng. Mohlala oa Mnd mouse o lokela ho lumella ho ithuta ka mekhoa e amang ho qala le tsoelo-pele ea ho senyeha ho itseng ha neuronal ho lefu la liphoofolo le tsa batho.
Ho theha mefuta ea lisele tsa batho tsa spinal muscular atrophy (SMA) ho etsisa motor neuron-specific phenotypes e tšoere senotlolo sa ho utloisisa pathogenesis ea lefu lena le senyang. Mona, re thehile mofuta oa lisele tse emelang haufi-ufi tsa SMA ka ho theola mofuta o khethollang lefu, survival motor neuron (SMN), liseleng tsa embryonic stem cell (hESCs). Boithuto ba rona ka mofuta ona oa sele bo bonts'itse hore ho theola SMN ha ho sitise ho kenella ha methapo ea kutlo kapa tlhahiso ea pele ea li-neurone tsa lesapo la mokokotlo. Haholo-holo, kholo ea axonal ea methapo ea kutlo ea lesapo la mokokotlo e ne e holofetse haholo mme li-neuron tsena tse etsisang mafu li ile tsa senyeha hamorao. Ho feta moo, mafu ana a phenotypes a bakoa ke SMN-full length (SMN-FL) empa eseng SMN-Delta 7 (e haelloang ke exon 7) knockdown, 'me e ne e le e tobileng ho li-neuron tsa mokokotlo oa mokokotlo. Ho khutlisa polelo ea SMN-FL ho ile ha ntlafatsa ka botlalo li-phenotypes tsohle tsa lefu lena, ho kenyelletsa le bofokoli bo itseng ba axonal le tahlehelo ea motor neuron. Qetellong, ho putlama ha SMN-FL ho lebisitse khatellong e feteletseng ea oxidative ea mitochondrial.
