Cov teebmeem ntawm General Cistanosides Mediated Specific Androgen Receptors Ntawm Synaptic Proteins Thiab Kev Paub Txog Kev Ua Haujlwm hauv SAMP8 nas Ⅱ

2 kev tshwm sim

2. 1 Cov nyhuv ntawm GCs ntawm kev kawm thiab kev nco hauv nas

Tom qab 30 hnub ntawm GC kev tswj hwm, kev khiav tawm latency ntawm qhov chaw thiab kev sim navigation maj mam txo nrog qhov nce ntawm cov hnub sim, thiab qhov kev poob qis yog qhov tseem ceeb tshaj plaws. Piv nrog rau pawg qauv, kev khiav tawm latency ntawm pawg GCs tau txo qis rau hnub 4 thiab 5 (P ＜ 0. 05); piv nrog GCs pawg, kev khiav tawm latency ntawm GCs + F pab pawg tau nce rau hnub 4 thiab 5. , kev khiav tawm latency ntawm GCs + ICI pawg tau txo qis rau hnub 4 thiab 5 (P ＜ 0. 05), tab sis tsis muaj qhov sib txawv ntawm 1 txog 3 d (P ＞ 0. 05). saib daim duab 1.

Daim duab 1 Kev khiav tawm latency ntawm txhua pab pawg nyob rau hauv qhov chaw ua haujlwm navigation sim

Nco tseg: Piv nrog rau cov qauv pab pawg, * P < {{0}}. 05; Piv nrog rau pawg GCs, # P < 0. 05

Daim duab 2 Tus naj npawb ntawm kev hla platform rau txhua pab pawg hauv qhov kev sim tshawb nrhiav qhov chaw

Nco tseg: Piv nrog rau cov qauv pab pawg, * P < {{0}}. 05; Piv nrog rau pawg GCs, # P < 0. 05

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Hauv kev tshawb nrhiav qhov chaw, piv nrog rau pawg qauv, tus naj npawb ntawm kev hla platform hauv GCs pawg tau nce ntxiv (P ＜ {{0}}}. 05); piv nrog rau pawg GCs, pawg GCs + F tau txo qis hauv cov neeg hla platform (P ＜ 0. 05), pawg GCs + ICI nce (P ＜ 0} . 05). Saib daim duab 2. Daim duab qhia txog kev ua luam dej tau pom tias qhov kev ua luam dej ntawm cov nas hauv pawg Model yog qhov tsis sib xws thiab tsis xwm yeem, thiab feem pua ​​​​ntawm cov sij hawm siv nyob rau hauv lub hom phiaj quadrant yog qhov qis tshaj (P <0. 05). Piv nrog rau Cov Qauv Pab Pawg, cov kev ua luam dej ntawm cov nas hauv GCs pawg tau ntau dua, nrog rau feem ntau ntawm lawv nyob rau hauv lub quadrant ntawm lub platform, thiab cov tsiaj siv feem pua ​​​​ntawm cov sij hawm nyob hauv lub hom phiaj quadrant (P ＜ 0. 05); piv nrog GCs pawg, kev hla ntawm GCs + F pab pawg Cov naj npawb ntawm cov platforms txo qis (P ＜ 0. 05), tab sis nce hauv GCs + ICI pawg (P ＜ 0. 05). Saib daim duab 3.

2. 2. Cov nyhuv ntawm GCs ntawm cov protein qhia ntawm SYN, PSD-95, thiab BDNF hauv nas hippocampus.

Piv nrog rau pawg qauv, cov protein qhia ntawm SYN, PSD{{0}}, thiab BDNF hauv pawg GCs tau nce ntau (P ＜ 0. 05); piv nrog rau pawg qauv, Piv nrog pab pawg, kev qhia ntawm PSD-95 protein nyob rau hauv GCs + F pab pawg thiab GCs + ICI pawg tau poob qis (P ＜ 0. 05); qhov kev qhia ntawm SYN protein nyob rau hauv GCs + F pawg tau nce ntau (P ＜ 0. 05); Cov protein qhia ntawm BDNF hauv GCs + F pawg thiab GCs + ICI pawg tau txo qis (P ＜0. 05). Saib daim duab 4.

Daim duab 3 Kev ua luam dej ntawm txhua pab pawg hauv qhov kev sim tshawb nrhiav qhov chaw

Lus Cim: A: Pawg qauv, B: GCs pawg, C: GCs + F pawg, D: GCs + ICI pawg, E: F pawg, F: ICI pawg

Daim duab 4 Western blot nrhiav pom ntawm PSD-95, SYN, thiab BDNF protein qhia hauv hippocampus ntawm txhua pab pawg

Lus Cim: A: SYN protein qhia, B: BDNF protein qhia, C: PSD-95 protein qhia.

Piv nrog rau pawg qauv, * P < {{0}}. 05; Piv nrog rau pawg GCs, # P < 0. 05

2. 3 GCs ntawm nas hippocampus cov ntaub so ntswg

Qhov cuam tshuam rau SYN, PSD{{0}}, thiab BDNF mＲNA qhia Piv nrog rau pawg qauv, pawg GCs tau muaj kev qhia ntau dua ntawm SYN, PSD-95, thiab BDNF mＲNA (P＜{ {7}} {{10}}5); piv nrog GCs pawg, GCs + F pawg, mRNA qhia theem ntawm PSD-95 hauv pawg GCs + ICI tau poob qis (P ＜ 0. 05); mRNA qhia ntawm SYN hauv GCs + F pab pawg tau nce ntxiv (P ＜ 0. 05); pawg GCs + F, GCs + Qhov mRNA qhia ntawm BDNF hauv pawg ICI tau txo qis (P ＜ 0. 05). Saib daim duab 5.

Daim duab 5 RT-PCR nrhiav pom ntawm PSD-95, SYN, thiab BDNF mＲNA qhia hauv hippocampus ntawm txhua pab pawg Lus Cim: A: SYN mＲNA qhia, B: PSD-95 mＲNA qhia, C: BDNF mＲNA qhia . Piv nrog rau pawg qauv, * P < 0. 05; Piv nrog rau pawg GCs, # P < 0. 05

3 Kev sib tham

Tsis muaj kev sib txuas ntawm protoplasmic ntawm cov neurons hauv cov qauv, thiab lawv tsuas yog tso siab rau kev sib txuas lus sib txuas los xa cov ntaub ntawv. Kev hloov pauv txawv txav hauv cov qauv synaptic thiab kev ua haujlwm yuav cuam tshuam rau kev xa xov zoo ntawm cov ntaub ntawv ntawm cov neurons, yog li nws feem ntau ntseeg tias AD kev paub txog kev ua haujlwm tsis zoo cuam tshuam nrog cov kev hloov pauv pathological hauv synapses [6]. Synaptic plasticity feem ntau yog hais txog kev hloov kho ntawm cov qauv thiab kev ua haujlwm ntawm kev sib txuas ntawm synaptic, suav nrog kev nce lossis txo qis ntawm cov synapses thiab kev hloov pauv hauv lub cev. Synaptic plasticity yog lub hauv paus ntawm kev kawm thiab kev nco, thiab nws qhov txo qis yog ib qho ntawm cov kab mob tseem ceeb ntawmAD cognitive dysfunction. Cov kev tshawb fawb yav dhau los tau pom tias GCs tuaj yeem tswj hwm cov yas yas los ntawm ntau lub tshuab los txhim kho kev txawj ntse. Nws tsim nyog sau cia tias GCs tuaj yeem nce qib androgen hauv cov tsiaj, thiab testosterone tuaj yeem txhim kho AD kev paub tsis meej [7]. Yog li, nws tau kwv yees tias GCs tuaj yeem txhim kho kev txawj ntse los ntawm kev ua haujlwm zoo li androgen.

Txoj kev tshawb no pom tias GCs tuaj yeem txo qis qhov kev khiav tawm ntawm SAMP8 nas thiab nce cov neeg hla platform, qhia tias GCs tuaj yeem txhim kho qhov kev paub tsis meej ntawm SAMP8 nas; thiab muab tsiaj flutamide (AR antagonist) tuaj yeem thaiv cov nyhuv ntawm GCs ntawm SAMP8 nas. Cov txiaj ntsig ntawm kev paub txog kev ua haujlwm hauv nas qhia tias tom qab kev tswj hwm ntawm flutamide, ua tiav kev sib xyaw ntawm GCs thiab ARＲ tuaj yeem raug thaiv thiab cov nyhuv tsis tuaj yeem tawm, uas yog, GCs tuaj yeem siv nws cov teebmeem los ntawm kev sib kho ARＲ tshwj xeeb.

Raws li lub cev muaj zog, testosterone tuaj yeem aromatize rau hauv dihydrotestosterone (DHT) thiab estradiol (E2) hauv lub cev. Hauv qhov kev sim no, kev tswj hwm ntawm fulvestrant (ER antagonist) rau cov tsiaj tuaj yeem txhim kho qhov kev paub tsis meej ntawm SAMP8 nas. Yog vim li cas tej zaum yuav yog tias fulvestrant thaiv cov kev khi tshwj xeeb ntawm E2 thiab ER hauv lub cev, ua rau muaj kev sib cais ntawm E2 hauv lub cev. E2 qib nce thiab nce, inhibiting metabolism ntawm testosterone rau E2. Ntawm qhov tsis sib xws, aromatization ntawm testosterone rau hauv DHT cov nyiaj them poob haujlwm nce, thiab kev sib xyaw nrog ARＲ nce, yog li txhim kho qhov kev paub tsis meej ntawm SAMP8 nas. Cov txiaj ntsig no tau txheeb xyuas ntxiv tias GCs tuaj yeem ua los ntawm kev kho kom haum xeeb tshwj xeeb AR Ｒ.

Nws yog qhov paub zoo tias kev paub tsis meej hauv cov neeg mob AD muaj feem cuam tshuam nrog synaptic plasticity. Cov kev tshawb fawb yav dhau los tau pom tias qhov kev qhia ntawm synapse-related proteins SYN, PSD-95, thiab BDNF hauv AD qauv tsiaj tau txo qis [8].

Cov txiaj ntsig ntawm qhov kev sim no tau pom tias tom qab kev tswj hwm ntawm GCs, kev qhia ntawm synapse-related proteins SYN, PSD-95, thiab BDNF tau nce, qhia tias GCs tuaj yeem txhim kho synaptic plasticity. Cov kev tshawb fawb tau pom tias BDNF tuaj yeem cuam tshuam nrog cov neurotrophin receptors, cuam tshuam rau kev tso tawm vesicles thiab neurotransmitters, yog li cuam tshuam rau kev kawm thiabkev txawj ntse muaj nuj nqi[9]. Cov txiaj ntsig ntawm qhov kev sim no pom tau tias piv nrog GCs pawg, kev qhia ntawm BDNF tau txo qis hauv GCs + F pab pawg thiab GCs + ICI pawg, qhia tias GCs tuaj yeem kho ARＲ kev koom tes hauv cov txheej txheem saum toj no cuam tshuam rau kev kawm thiab kev txawj ntse. Synaptophysin (SYN) yog calcium-binding protein nyob rau hauv lub synaptic vesicle membrane.

Nws muaj nyob rau hauv nruab nrab thiab peripheral paj terminals ntawm yuav luag tag nrho cov tsiaj, thiab tej zaum yuav koom nyob rau hauv lub tsim ntawm synaptic vesicle-specific channels, thiab tseem muaj feem xyuam rau kev thauj ntawm vesicles thiab tso tawm ntawm neurotransmitters [10]. Postsynaptic density protein (PSD-95) yog nyob rau hauv lub postsynaptic membrane thiab yog lub luag hauj lwm rau tau txais neurotransmitters tso tawm los ntawm lub presynaptic thiab koom nyob rau hauv regulating synaptic teeb liab kis tau tus mob thiab synaptic plasticity. Yog li ntawd, SYN thiab PSD -95 raug suav hais tias yog ib qho cim rau kev ntsuas kev ua haujlwm ntawm synaptic thiab kev ua haujlwm ntawm plasticity [11]. Cov txiaj ntsig ntawm qhov kev sim no pom tau tias piv nrog GCs pawg, kev qhia ntawm SYN nce thiab kev qhia ntawm PSD-95 poob qis tom qab cov tsiaj tau txais flutamide, qhia tias GCs tuaj yeem kho AR los tswj cov kab mob postsynaptic, tab sis tsis yog. presynaptic daim nyias nyias. Cov nyhuv tsis tshwj xeeb kho AR Ｒ. Piv nrog rau cov pab pawg GCs, cov lus qhia theem ntawm BDNF thiab PSD-95 poob qis tom qab cov tsiaj tau txais fulvestrant, thiab qhov txo qis yog qhov tseem ceeb tshaj li ntawm pawg GCs + F, uas tau txheeb xyuas ntxiv tias GCs tuaj yeem ua lub luag haujlwm. los ntawm kev kho kom haum xeeb tshwj xeeb AR Ｒ.

Hauv cov ntsiab lus, GCs tuaj yeem kho qhov tshwj xeeb ARＲ los tswj synaptic plasticity, yog li txhim kho AD kev paub tsis meej, uas yuav muab cov tswv yim tshiab rau kev siv GCs hauv kev tiv thaiv thiabkev kho mob ntawm AD.

Cov ntaub ntawv

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