Highlighting Immune System and Stress in Major Depressive Disorder, Parkinson's, Thiab Alzheimer's Disease, Nrog Kev Sib Txuas Nrog Serotonin Part 1

Abstract:

Muaj kev lees paub tias ob qho tib si kev ntxhov siab thiab kev tiv thaiv kab mob yog qhov tseem ceeb hauv ntau yam kab mob neurological. Tsis tas li ntawd, muaj lub luag haujlwm tseem ceeb ntawm ntau lub paj hlwb uas txuas cov yam ntxwv no rau ntau yam kab mob hauv lub paj hlwb, nrog rau qhov tshwj xeeb hauv daim ntawv no ntawm serotonin. Raws li, nws paub tias qhov tsis txaus ntseeg hauv kev ntxhov siab tuaj yeem txhawb nqa ntau yam neuropsychiatric lossis neurodegenerative pathologies.

Muaj kev sib raug zoo heev ntawm kev tiv thaiv kab mob thiab kev nco. Peb lub cev tiv thaiv kab mob yog lub cev tiv thaiv kev tiv thaiv uas tiv thaiv peb ntawm cov kab mob, kab mob, kab mob, thiab lwm yam kab mob. Txawm li cas los xij, kev tshawb fawb tsis ntev los no qhia tau hais tias lub cev tiv thaiv kab mob tuaj yeem cuam tshuam rau peb lub cim xeeb thiab kev txawj ntse.

Ib txoj kev tshawb nrhiav pom muaj kev sib txuas zoo ntawm kev txo qis ntawm lub cev tiv thaiv kab mob thiab kev paub txog kev poob qis hauv cov neeg laus. Qhov no qhia tau hais tias thaum peb muaj hnub nyoog, kev ua haujlwm ntawm peb lub cev tiv thaiv kab mob pib poob qis, uas tuaj yeem ua rau kev txawj ntse poob. Tsis tas li ntawd, muaj qhov tshwm sim zoo sib xws hauv qee cov neeg uas muaj kab mob autoimmune. Cov neeg mob no tuaj yeem ntsib cov tsos mob xws li kev paub tsis meej thiab tsis nco qab, uas tej zaum yuav yog vim lub cev tiv thaiv kab mob tawm tsam cov neurons thiab lub cev tiv thaiv kab mob hauv lub hlwb.

Txawm li cas los xij, kev tshawb fawb zoo kuj tseem qhia tau tias lub cev tsis muaj zog tuaj yeem txhim kho peb lub cim xeeb thiab kev txawj ntse. Ib txoj kev tshawb nrhiav pom tias kev txhawb nqa kev ua haujlwm ntawm lub cev tiv thaiv kab mob los ntawm kev txhaj tshuaj tuaj yeem txhim kho kev nco thiab kev txawj ntse hauv cov neeg laus. Qhov no yog vim qhov tso tawm ntawm cov tshuaj los ntawm lub cev tiv thaiv kab mob uas muaj cov tshuaj tiv thaiv kab mob hauv lub hlwb, yog li txhim kho kev noj qab haus huv ntawm cov neurons thiab txhim kho kev nco thiab kev txawj ntse.

Yog li ntawd, muaj kev sib raug zoo thiab hloov maj mam ntawm kev tiv thaiv kab mob thiab kev nco. Thaum muaj cov xwm txheej uas lub cev tiv thaiv kab mob tuaj yeem cuam tshuam tsis zoo rau kev nco, muaj lwm yam mob uas lub cev tiv thaiv kab mob tuaj yeem txhim kho peb lub cim xeeb thiab kev txawj ntse. Yog li ntawd, peb yuav tsum tau tswj kom txaus so thiab tawm dag zog, noj kom zoo, thiab ntxiv dag zog rau kev ua haujlwm ntawm lub cev tiv thaiv kab mob los ntawm kev txhaj tshuaj tiv thaiv thiab lwm yam. Ua li no, peb tuaj yeem tswj hwm kev txawj ntse thiab kev nco zoo thiab ua tau raws li ntau yam kev cov nyom thiab lub sijhawm. Nws pom tau tias peb yuav tsum txhim kho peb lub cim xeeb. Cistanche tuaj yeem pab peb txhim kho kev nco zoo vim Cistanche yog cov khoom siv tshuaj suav tshuaj suav nrog ntau yam tshwj xeeb, ib qho ntawm kev txhim kho kev nco. Kev ua tau zoo ntawm cov nqaij minced yog los ntawm ntau yam khoom xyaw uas nws muaj, suav nrog carboxylic acid, polysaccharides, flavonoids, thiab lwm yam. Cov khoom xyaw no tuaj yeem txhawb lub hlwb kev noj qab haus huv los ntawm ntau txoj hauv kev.

Nyem paub 10 txoj hauv kev los txhim kho kev nco

Ntawm no, peb tham txog qee qhov tseeb uas txuas nrog kev nyuaj siab loj, Alzheimer's, thiab Parkinson's rau kev ntxhov siab thiab kev tiv thaiv kab mob, nrog rau kev sib txuas ntawm cov lus teb thiab cov teeb liab serotonergic. Cov no yog cov ncauj lus tseem ceeb ntawm kev tshawb nrhiav uas yuav ua rau muaj kev kho tshiab lossis zoo dua, txhim kho lub neej zoo ntawm cov neeg mob uas raug kev txom nyem los ntawm cov xwm txheej no.

Ntsiab lus:

Kev ntxhov siab; tiv thaiv kab mob; kev nyuaj siab loj; Alzheimer tus kab mob; Tus kab mob Parkinson; tshuaj serotonin.

1. Taw qhia

Muaj kev paub ntau ntxiv tias ob qho tib si kev ntxhov siab thiab kev tiv thaiv kab mob yog qhov tseem ceeb hauv ntau yam kab mob hauv lub paj hlwb uas yog, tig mus, cuam tshuam nrog ntau yam sib txawv, xws li tus naj npawb ntawm cov neurotransmitters uas muaj nyob hauv tib neeg lub cev, thaum twg los tau [1,2 ] (Daim duab 1). Cov lus teb sib txawv rau kev ntxhov siab muaj nyob, nyob ntawm seb nws puas mob lossis mob ntev.

Qhov thib ib yog ib qho physiological teb, whereas qhov thib ob yog, feem ntau, teeb meem, dysregulating tus raug thiab noj qab haus huv kev nyuaj siab teb. Ntawm no, kev tswj tsis tau, kev ntxhov siab ntev yuav txhawb nqa ntau yam kev hloov pauv hauv ob peb lub hauv paus paj hlwb, neuropsychiatric thiab neurodegenerative disorders [3,4].

Tseeb tiag, kev tshawb fawb hauv neuropsychiatry qhia tias kev ntxhov siab ntsig txog kev txawv txav muaj lub luag haujlwm tseem ceeb hauv kev tsim cov kab mob ntawm cov kab mob no. Cov kev tshawb fawb ntxiv kuj tau hais tias qhov tsis txaus ntseeg hauv cov lus teb kev ntxhov siab muaj lub luag haujlwm tseem ceeb hauv cov kab mob neurodegenerative [4].

Lub serotonergic signaling nyob rau hauv lub hlwb yog cuam tshuam los ntawm ntau yam ntawm cov kev ntxhov siab teb, thiab cov tshuaj uas cuam tshuam nrog serotonergic txoj kev yuav cuam tshuam cov teebmeem ntawm kev ntxhov siab [5].

Ib qho piv txwv uas qhia txog qhov kev sib raug zoo no yog ib qho kev sim ua nrog cynomolgus liab uas tau sib cais los ntawm lawv cov resilience rau kev ntxhov siab xws li siab, nruab nrab, thiab qis resilience.

Nyob rau hauv txoj kev tshawb no, cov tsiaj rhiab heev rau kev ntxhov siab tau qhia tsawg dua nyob rau hauv ntau cov noob uas tseem ceeb rau kev ua haujlwm ntawm serotonergic system.

Cov noob no suav nrog Plasmacytoma nthuav tawm cov ntawv sau tseg 1 (Pet-1), tryptophan hydroxylase (Tph2), serotonin transporter (SERT), thiab serotonin 1A receptor (5-HT1A).

Tag nrho cov proteins no yog ib qho tseem ceeb rau kev txhim kho lub hlwb serotonergic systems, ntau lawm, thauj, thiab serotonin zog, raws li. Nyob rau hauv lem, nyob rau hauv tib txoj kev tshawb no, muaj ib tug nce nyob rau hauv qhov kev qhia ntawm corticotropin-tso tshuaj hormone (CRH) nyob rau hauv cov tsiaj muaj kev nyuaj siab rau cov kev nyuaj siab dua piv rau cov resilient ntau [6]. Yog li ntawd, tag nrho cov ntaub ntawv no qhia tias serotonin thiab rhiab heev rau kev ntxhov siab koom nrog.

Cov teebmeem ntawm kev ntxhov siab ntawm cov kab mob serotonergic tuaj yeem ua tau ntev thiab koom nrog kev hloov pauv hauv cov noob caj noob ces thiab epigenetic qhia, ua rau muaj kev hloov pauv hauv cov kab ke no [7]. Tsis tas li ntawd, cov kev ntxhov siab tuaj yeem txhim kho lossis txo qis kev tiv thaiv kab mob. Ntau cov txheej txheem lom neeg, xws li kev ntxhov siab, nco, pw tsaug zog, thiab pub mis, yog hloov kho los ntawm peripheral cytokines, qhov tseeb uas qhia txog kev muaj kev sib txuas lus ntawm lub cev tiv thaiv kab mob thiab lub hlwb [2]. Kev hloov pauv hauv lub hlwb yog txuam nrog kev dementia thiab kev nyuaj siab, qhov twg serotonin kuj muaj qee yam tseem ceeb (Daim duab 2).

Ib qho piv txwv paub zoo yog kev nyuaj siab cuam tshuam nrog rheumatoid mob caj dab. Tsis tas li ntawd, ntau cov kev tshawb fawb soj ntsuam tau ua pov thawj tias cov neeg mob kev nyuaj siab tau nce ntshav qib ntawm proinflammatory cytokines [8]. Tsis tas li ntawd, hais txog tus kab mob Parkinson, tseem muaj cov ntaub ntawv pov thawj txhawb nqa los ntawm kev kis mob, tshuaj, thiab kev tshawb nrhiav caj ces uas cov txheej txheem inflammatory yog qhov tseem ceeb rau kev kis kab mob [9].

Yog li, kawm txog cov txheej txheem inflammatory, cov lus teb kev ntxhov siab, thiab lawv cov kev sib txuas rau ib leeg thiab cov txheej txheem neuronal, yog qhov tseem ceeb rau kev nkag siab tob txog cov kab mob cuam tshuam loj heev, Kev Nyuaj Siab Loj (MDD), Parkinson's disease (PD), thiab Alzheimer's disease (AD) .

Daim duab 2. Serotonin, ib qho neurotransmitter nrog lub luag haujlwm tseem ceeb hauv cov txheej txheem ntawm kev sib kis ntawm neuronal, kuj yog ib qho tseem ceeb hauv kev sib haum xeeb hauv kev ntxhov siab thiab kev tiv thaiv kab mob hauv ntau yam pathologies, xws li MDD, AD, thiab PD. Nyob rau hauv daim duab no, cov qauv tshuaj sawv cev rau serotonin thiab cov ntawv sau qhia txog qee yam haujlwm tseem ceeb ntawm cov neurotransmitter no hauv cov ntsiab lus ntawm tsab xov xwm no. Tsim nrog BioRender.com.

2. Kev ntxhov siab

2.1. Nyob rau hauv Major Depressive Disorder

Ntau yam ntawm lub cev muaj feem xyuam rau cov lus teb kev ntxhov siab, ntawm kev nco txog lub paj hlwb autonomic thiab hypothalamic-pituitary-adrenal (HPA) axis. Kev ua kom cov axis tau hais los saum toj no ua rau nce qib ntawm glucocorticoid qib [4,10]. CRH koom nrog hauv HPA axis hauv ib txoj hauv kev uas txhawb nqa lub hypophysis kom tso tawm adrenocorticotropin hormone (ACTH) thiab, yog li, tswj kev tso tawm glucocorticoid thiab ntau lawm.

MDD yog ib qho kev puas siab puas ntsws loj, uas muaj ntau qhov kev xav los piav qhia nws cov kab mob pathophysiology. Txawm li cas los xij, qis qis ntawm serotonin nyob rau hauv lub hauv paus paj hlwb yog ib qho ntawm cov kev xav uas feem ntau txhawb los ntawm cov zej zog kev tshawb fawb, txawm tias xav tau kev qhia meej [11]. Tus kab mob no muaj cov txheej txheem nyuaj thiab qee zaum tsis paub meej txog cov txheej txheem lom neeg muaj feem cuam tshuam rau hauv nws cov etiology, suav nrog kev ntxhov siab ntawm kev puas siab puas ntsws; melancholia thiab atypical nta yog, ntsig txog, txuas rau lub siab ua haujlwm ntawm kev ntxhov siab thiab nws cov kev txwv tsis pub [2,12,13].

Cov ntaub ntawv pov thawj rau kev sib cuam tshuam tseem ceeb ntawm qhov kev ntxhov siab thiab MDD tshwm sim hauv ntau yam. Nws paub tias cov tshuaj tiv thaiv kev ntxhov siab txo qis HPA axis muaj nuj nqi thiab tias los ntawm kev tawm tsam CRH, muaj qhov txo qis ntawm cov lus teb kev ntxhov siab [2]. Qhia txog lub luag haujlwm ntawm kev ntxhov siab hauv MDD, kwv yees li 50% ntawm cov neeg mob uas muaj kev nyuaj siab qhia HPA axis ua haujlwm tsis zoo, ua rau muaj kev cuam tshuam tsis zoo ntawm corticosteroid secretion. Tsis tas li ntawd, nce CRH mRNA qhia hauv hypothalamus tau pom nyob rau hauv cov neeg mob MDD, nrog rau kev nce qib hauv cerebrospinal kua [4].

Raws li tau hais los saum no, los ntawm kev ua rau HPA axis, kev ntxhov siab ua rau kev tso tawm ntawm glucocorticoids. Hauv kev tshawb fawb hauv cov nas, qhov kev ncua ntev ntawm corticosterone (glucocorticoid hauv cov nas) ua rau muaj kev hloov pauv hauv morphological hauv neuronal dendrites, txhawb kev atrophy [14,15]. Tsis tas li ntawd, synapse poob thiab neuronal tuag los ntawm glutamate excitotoxicity tau pom [16-18].

Tag nrho cov kev tshawb pom no cuam tshuam nrog kev paub tsis meej, ua rau muaj kab mob xws li MDD. Kuj tseem muaj pov thawj tias MDD cuam tshuam txog qhov txo qis ntawm hippocampus thiab prefrontal cortex, uas muaj kev ntxhov siab ntev ua lub luag haujlwm tseem ceeb. Tseeb, nyob rau hauv kev tshawb fawb nrog cov tsiaj qauv ntawm kev nyuaj siab tshwm sim los ntawm kev ntxhov siab, nws tau pom tias nyob rau hauv txhua ntu ntawm kev nyuaj siab, ib tug ntau pronounced txo ntawm lub hlwb tau pom [19]. Qee cov kev tshawb fawb kev sim kuj tau pom tias qhov nce siab hauv kev ntxhov siab hauv nas yog cuam tshuam nrog kev txo qis hauv txoj kev ua haujlwm ntawm 5-HT1A receptor, ua kom cov serotonin 2 receptor (5-HT2), thiab serotonin 1b. receptor (5-HT1B).

Yog li, nws yog qhov tsis txaus ntseeg tias kev ntxhov siab vim kev hloov pauv cuam tshuam rau serotonergic system koom nrog kev nyuaj siab [20]. Tsis tas li ntawd, hauv cov tsiaj nyeg, nws tau pom tias hauv vivo concentrations ntawm lub hlwb metabolites txo qis, tshwj xeeb tshaj yog N-acetyl-aspartate (−13%), creatine thiab phosphocreatine (−15%), thiab choline-muaj cov tebchaw (−13%).

Cov teebmeem ntawm kev ntxhov siab no tau tiv thaiv los ntawm kev tswj hwm ntawm tianeptine, tshuaj tiv thaiv kev ntxhov siab [21]. Hauv lwm txoj kev tshawb fawb, MDD tau cuam tshuam nrog ntau dua oxidative kev nyuaj siab malondialdehyde qib thiab qis zinc thiab uric acid qib, piv rau kev noj qab haus huv tswj [22]. Lwm cov kev tshawb fawb taw qhia tias kev ntxhov siab cuam tshuam nrog kev hloov pauv hauv tib neeg glucocorticoid receptor gene (NR3C1) [23,24], tib neeg serotonin transporter gene (SLC6A4) [25,26], hlwb-derived neurotrophic factor gene, (BDNF) [27] ], FK506 binding protein 5 gene (FKBP5) [28], thiab spindle thiab kinetochore txuam complex 2 genes (SKA2) [29], tau pom tias muaj feem cuam tshuam nrog kev kuaj mob ntawm MDD. Ib lo lus nug tseem ceeb yog seb qhov kev ntxhov siab puas yog qhov ua rau lossis kev nyuaj siab [4]. Qhov no yog qhov nthuav thiab cog lus tsom mus rau kev tshawb fawb.

Cov kev hloov pauv hauv cov kab ke serotonergic cuam tshuam nrog kev xav thiab kev ntxhov siab, nrog rau kev ua haujlwm rau kev ntxhov siab, tau tham dav dav thiab yog cov ncauj lus tseem ceeb. Ntau qhov kev tshawb fawb tau tsom mus rau kev sib raug zoo ntawm kev xaiv serotonin reuptake inhibitors (SSRIs-cov tshuaj nquag siv hauv kev kho kev nyuaj siab, uas ua rau kom cov cellular concentration ntawm serotonin) thiab ntau yam ntawm HPA axis [5,30].

Ntau cov ntaub ntawv pov thawj qhia tau hais tias qhov kev tswj hwm mob hnyav ntawm fluoxetine (SSRI feem ntau raug kho rau MDD) ua rau muaj kev nce ntxiv hauv cov ntsiab lus ntawm serotonin extracellular hauv hypothalamus, suav nrog hauv paraventricular nucleus nucleus uas yog enriched hauv CRH-CRH-muaj. neurons. Yog li, cov ntaub ntawv pov thawj pom tau hais tias kev tswj hwm tus mob hnyav ntawm cov tshuaj no ua rau muaj kev ua haujlwm ntawm HPA axis, suav nrog nce qib ntawm CRH mRNA, nce kev qhia ntawm cov ntsiab lus hloov pauv, thiab nce siab ntawm ACTH thiab corticosterone hauv cov ntshav.

Txawm li cas los xij, cov kev tshawb fawb tib yam no tau pom tias serotonin tuaj yeem qhib / txwv tsis pub HPA axis nyob rau hauv koob tshuaj, lub sijhawm ua haujlwm, thiab subtype ntawm serotonergic receptor koom nrog. Piv txwv li, kev tswj hwm ntawm 5-HT1A agonists rau hauv paraventricular nucleus inhibits cov haujlwm ntawm HPA axis ntawm cov tshuaj tsawg, ua rau muaj qhov cuam tshuam ntawm qhov ntau npaum li cas [31].

Tsis tas li ntawd, ntau daim ntawv pov thawj qhia tau hais tias kev tswj hwm ntev ntawm SSRIs txo cov haujlwm ntawm HPA axis, yog li txo cov ntshav plasma ntawm ACTH, thiab CRH mRNA hauv paraventricular nucleus [32].

2.2. Hauv Alzheimer's Disease

Kev ntxhov siab ntev yog ib qho kev pheej hmoo cuam tshuam nrog AD pathogenesis [33,34]. Ntau qhov kev tshawb fawb qhia tias ntau yam kev ntxhov siab nce qib ntawm ntau yam kab mob cuam tshuam nrog AD, uas yog amyloid precursor protein, A peptide, thiab intracellular neurofibrillary tangles. Tsis tas li ntawd, kev poob ntawm synaptic plasticity kuj tau pom, nrog rau kev nce hauv hyperphosphorylated tau, intracellularly [33,35,36].

Thaum lub HPA axis tau qhib kom muaj ntau yam hauv MDD, hauv AD, nws tsuas yog ua haujlwm nruab nrab xwb, uas tuaj yeem piav qhia los ntawm kev puas tsuaj thaum ntxov hauv hippocampus los ntawm tus kab mob no. Txawm hais tias cortisol thiab CRH tuaj yeem koom nrog hauv MDD, tsis muaj pov thawj tseeb txog seb lawv puas tau koom nrog qhov kev puas tsuaj loj uas hippocampus raug kev txom nyem thaum AD.

Qhov ntawd tsis tau txhais hais tias cortisol tsis ua lub luag haujlwm hauv AD vim tias nws muaj kev cuam tshuam nrog cov lus teb inflammatory hauv AD [37]. Cov qib cortisol hauv plasma tau nce nrog AD [37] thiab cov qib ntawm salivary cortisol muaj feem cuam tshuam nrog kev txuas ntxiv AD [38], ntxiv rau qhov tseeb tias muaj kev sib raug zoo ntawm cov qib cortisol hauv ntshav thiab cerebrospinal kua (CSF). Tsis tas li ntawd, neuronal poob tau pom nyob rau hauv hippocampus ntawm nas uas muaj kev ntxhov siab / kho nrog corticosteroids [39].

Nws tau xav tias, thaum lub sij hawm ntev ntawm kev ntxhov siab, kev tswj hwm ntawm glucocorticoids yuav ua rau lub hippocampus, tshwj xeeb tshaj yog cov nas laus. Nyob rau hauv cov xwm txheej ib txwm muaj, HPA axis yog inhibited los ntawm hippocampus, yog li qhov kev puas tsuaj uas hippocampus raug kev txom nyem yuav ua rau muaj kev ua haujlwm ntawm cov axis no, ua rau muaj kev ua haujlwm ntau ntawm glucocorticoid ntau ntau, ua rau muaj kev puas tsuaj hauv hippocampus. Qhov degree uas HPA axis qhib tau txuas nrog kev paub tsis meej thiab hippocampal atrophy [40–42].

Tseeb, qhov poob ntawm hippocampal ntim hauv cov neeg mob uas muaj kev nyuaj siab unipolar tau tshaj tawm [43], uas tuaj yeem yog qhov tshwm sim ncaj qha ntawm kev rov ua dua lub sijhawm ntawm kev nyuaj siab. Lub hippocampus nyob rau hauv cov neeg mob kev nyuaj siab qhia tau hais tias tsis muaj loj heev cell poob los yog pathological hloov raws li nyob rau hauv cov neeg mob nrog AD [37]. Txawm li cas los xij, qhov txo qis hauv hippocampus tsis txhais hais tias cell poob vim nws tuaj yeem hloov pauv hauv cov ntsiab lus dej, raws li tau hais tseg [44,45].

Tsis tas li ntawd, kev ua kom HPA axis thiab cov teeb meem kev paub hauv AD tuaj yeem piav qhia los ntawm cov txheej txheem txuas ntxiv ntawm tus kab mob no hauv hippocampus, tsis muaj cortisol yog qhov tseem ceeb. Lwm cov kev tshawb fawb taw qhia tias, los ntawm cov qauv tsiaj, cov kab mob ntawm AD tau txhim kho los ntawm kev cuam tshuam rau kev ntxhov siab thiab qib siab ntawm cortisol.

Tseeb tiag, dexamethasone txoj kev kho mob tau nce qib ntawm APP thiab tseem txhawb kev tsim cov cerebral amyloid plaques [46]. Tsis tas li ntawd, nyob rau hauv cov nas qus, kev kho mob nrog glucocorticoids, nrog rau kev cuam tshuam rau kev ntxhov siab ntev, induced hyperphosphorylation ntawm tau, thawj kauj ruam hauv keeb kwm ntawm neurofibrillary tangles [47]. Kev ntxhov siab ntev kuj tuaj yeem ua rau muaj kev cuam tshuam ntawm cov ntshav- hlwb teeb meem (BBB) ​​thiab ua rau cov kab mob neuroinflammation uas ua rau cov txiaj ntsig AD ua rau hnyav dua. Qhov kev ua haujlwm BBB no ua rau txo qis A nkag los ntawm lub hlwb mus rau cov ntshav ncig, ua rau nws tsub zuj zuj [48].

Lwm txoj kev tshawb fawb, hauv cov nas, tau qhia txog kev sib raug zoo ntawm kev ntxhov siab thiab qib peptide hauv lub hlwb. Tseeb tiag, kev ntxhov siab ntev nce qib ntawm A peptide los ntawm 84% [49]. Ntxiv mus, nyob rau hauv ib txoj kev tshawb no nrog tus tsiaj qauv ntawm AD APPV717I-CT100 (transgenic nas), nws tau tshaj tawm tias kev ntxhov siab tsis tu ncua cuam tshuam nrog cov teeb meem kev coj cwj pwm, amyloid deposits extracellularly, thiab neurodegeneration [50]. 

Lwm txoj kev tshawb fawb tau qhia tias tom qab kho triple transgenic A PP / PS1 / MAPT nas nrog dexamethasone, nce qib ntawm AD biomarkers xws li A precursor protein (A PP) thiab A tau pom [46].

Yav dhau los, nws tau xav tias tsuas yog qhov tsis ua haujlwm ntawm cholinergic system yog lub luag haujlwm rau cov tsos mob tshwm sim hauv AD [51]. Txawm li cas los xij, lub luag haujlwm tseem ceeb ntawm cov kab ke monoaminergic hauv AD tau nce ntxiv los ntawm cov zej zog kev tshawb fawb, txhawb nqa los ntawm ntau qhov kev tshaj tawm. Tshwj xeeb, serotonergic system zoo nkaus li ua lub luag haujlwm tseem ceeb hauv kev kawm thiab kev nco qab los ntawm kev sib cuam tshuam nrog lwm cov kab mob neurotransmitter, xws li cholinergic, GABAergic, dopaminergic, thiab glutaminergic systems [52,53].

Nrog rau qhov tshwj xeeb, tsis ntev los no tau tsim serotonergic antidepressants xws li vortioxetine, ntxiv rau inhibiting serotonin thauj, yog serotonergic receptor antagonists tseem ceeb rau kev paub txog kev ua haujlwm, xws li nyob rau hauv rooj plaub ntawm serotonin 7 receptor (5-HT7). Yog li, hauv cov neeg mob uas muaj kev nyuaj siab thiab mob AD, cov tshuaj no tau pom tias muaj kev txhim kho tseem ceeb hauv kev paub txog kev ua haujlwm piv rau cov tshuaj SSRIs, yog li dhau los ua ib lub ntsiab lus zoo heev ntawm kev kawm [54]. Zuag qhia tag nrho, muaj qhov cuam tshuam tseem ceeb ntawm serotonergic system ntawm AD.

Raws li tau hais ua ntej, kev ntxhov siab cuam tshuam rau ntau yam ntawm serotonergic signaling hauv lub hlwb thiab cov tshuaj serotonergic tuaj yeem hloov kho cov teebmeem ntawm kev ntxhov siab. Qhov no ua rau qhov tseem ceeb ntawm kev tshawb xyuas qhov teeb meem no: kev kawm txog seb serotonin cuam tshuam li cas rau kev ntxhov siab hauv AD.

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