Ya’kubî, Ülkeler Kitabı (Kitabü’l Büldan)

Persistent impaired glucose metabolism in a zebrafish hyperglycemia model

Katiucia Marques Capiotti, Régis Antonioli Junior, Luiza Wilges Kist, Maurício Reis Bogo, Carla Denise Bonan, Rosane Souza da Silva.

Artigo publicado no periódico

Comparative Biochemistry and Physiology, Parte B 171:58-65. 2014  

(doi: 10.1016/j.cbpb.2014.03.005)  

    3.2 CAPÍTULO II

ARTIGO CIENTÍFICO

Hyperglicemia induces memory impairment linked to increased acetilcholinesterase activity in zebrafish (Danio rerio).

Katiucia Marques Capiotti, Daiani Almeida De Moraes, Fabiano Peres Menezes, Luiza Wilges Kist, Maurício Reis Bogo, Rosane Souza Da Silva.

Artigo publicado no periódico

Behavioural Brain Reasearch, 274:319-25. 2014. (doi: 10.1016/j.bbr.2014.08.033)

322 K.M.Capiottietal./BehaviouralBrainResearch274(2014)319–325

3.1. Inhibit oryavoidancetask

Inordert oevaluat eifhyperglycem iacouldbecausingadefi cit onm em ory,w esubm it t edt heanim alst ot heinhibit oryavoidance paradigm .Allanim alsgroupshadt heirm em oryt est ed24haft er t raining.Im port ant ly,nodifferencesw erefoundbet w eent rain- inglat enciesforallgroups.Ourresult sdem onst rat edt hatanim als exposedt o111m Mglucosehadadecreaseont helat encyont he t estsession(p<0.0001)(Fig.1).Therefore,t oascert aint hathyper- glycem iacont inuest oaffectt hem em oryevenaft er7or14daysof glucosew ashout ,w eperform edt hesam eexperim entofinhibit ory avoidancew it h w ashoutgroups.Our result sdem onst rat edt hat w ashoutgroups(7and14days)alsodem onst rat edadecreaseof lat encyont estsession(p<0.0001andp<0.05,respect ively)(Fig.1). How ever,t hese14daysofglucosew it hdraw alseem t oprom ot e anim provem ent inm em ory com paredt ot he7daysofglucose w it hdraw al(Fig.1).

3.2. Locomotoract ivityassessment

Toevaluat eif hyperglycem iacould alt er locom ot or param e- t ers,w efi rst lyobservedt helocom ot oract ivit yofanim alst reat ed in 111m M glucose and w ashout group (7 days). Our result s dem onst rat ed t hat t here are no differences in dist ance t rav- eled[ F(2,39)=0.2772;p=0.7594]andm eanspeed[ F(2,39)=0.1729;

p=0.8418]bet w eencont rol,111m Mglucose-t reat edandw ashout group(dat anotshow ed).

3.3. Effectofhyperglycemiaonacet ylcholinest erase(AChE) activity

Aft erverifyt hathyperglycem iam odifi esm em oryparam et ers inzebrafi sh,w eobserved if t heglucoset reat m ent w asablet o inducechangesonAChEact ivit yinbrainfromadultzebrafi sh.Our result sdem onst rat edt hatAChEact ivit yw assignifi cant lyincreased in111m M glucosegroup(15%)[ F_(2,25)=16.35; p=0.0001] w hen com paredt ocont rolgroup(Fig.2).TherearenochangesonAChE act ivit yinglucose-w ashout7daysgroupw hencom paredt ocon- t rolgroup,butw hencom paredt o111m MGlucosegroupt herew as areduct ionofAChEact ivit y(25%),[ F(2,25)=16.35p=0.0001].

Fi g.1.111m Mglucoseandw ashout(7and14days)t reat m entinduceslong- t ermm em orydefi citsininhibitoryavoidancet ask.C:cont rol-t r eat edanim als,Glu: 111m Mglucose-t r eat edanim als,W7:W ashout7days–t r eat edanim als,W14: W ashout14days–t r eat edanim als.Cont rolanim alsw erem anipulatedsim ilarly butexposedt ow at eronly.Barsindicat eanim als’m eanlat encies+S.E.Mt ocross com part m ent(inseconds)int raining(TR)andt est(TT)sessions.Atleasteleven zebrafi shw er eusedforeachgr oup.*p<0.05,**p<0.01and***p<0.0001indicat e st at ist icallysignifi cantdifferencebetw eenlat enciest estsessionsforcont rolgroup anim als.

Fi g.2.Effectof111m Mglucoseandglucose-w ashout(7days)t reat m entonacet yl- cholinehydrolysis.**indicat essignifi cantly differ encew hencom paredt ot he contr olgroup.#indicat essignifi cantlydiffer encew hencom paredt ot he111m M glucosegr oup.Dat ar epresentm eans±S.E.Moffourdifferentexperim ents,each oneperform edint riplicat e.Dat aw er eanalyzedst at ist icallybyone-w ayANOVA follow edbyTukeyt estasposthoct est ,consider ingap<0.05signifi cant.Thespe- cifi cenzym eact ivit yisrepor tedasm icrom oleoft hiocholinereleasedperhourper m illigramofprot ein.

3.4. Effectofgalant aminet reat mentonhyperglycemiczebrafish

3.4.1. Inhibitoravoidancetask

Inordert oevaluat eifgalant am inecouldreverset hedefi citon m em orycausedbyhyperglycem ia,w esubm it t edt heanim alst o t heinhibit oryavoidanceparadigm2haft ergalant am inet reat m ent . Ourresult sdem onst rat edt hatgalant am inew asablet oreverset he m em orydefi citcausedbyhyperglycem ia(p<0.001)(Fig.3).Im por- t ant ly,nodifferencesw erefoundbet w eent raininglat enciesforall groups.

3.4.2. Locomot oractivit yassessment

To evaluat e if galant am ine could alt er locom ot or param e- t ers, w e observed t he locom ot or act ivit y of anim als t reat ed incont rol,galant am ine0.05ng/g,111m M glucoseand 111m M glucose+galant am inegroup.Our result sdem onst rat ed t hat t he t reat m ent w it h galant am ine decreased t he dist ance t raveled [ F(3,28)=7.145;p=0.0013](Fig.4A)andm eanspeed[ F(3,30)=4.693;

p=0.0072](Fig.4B)incom parisont o111m Mglucosegroup.Galan- t am inebyit selfshow ednost at ist icaldifferencefrom t hesaline group.

3.5. Effectofhyperglycemiaonache,insulinreceptors,andglut-3 expressioninbrainofzebrafish

Toevaluat ew het hert het reat m entw it h111m Mglucoseand7 daysofw ashoutcouldalt ert hegeneexpressionofAChE,real-t im e

Fi g.3.Hyperglycem iacausedby111m Mglucoset reat m entby14dayscaused cognit ivedefi citst hatw ererever sedbygalant am ine(0.05ng/g).S:saline-t reat ed anim als,Gal:Galant am ine-t reatedanim als,Glu:111m Mglucose-t r eat edanim als, Glu+Gal:111m MGlucose+Galant am ine-t reat edanim als.Atleastninezebrafi sh w ereusedforeachgroup.Anim alsr eceivedsingleint r aper it onealinject iongalan- t am ine(0.05ng/g)2hbeforet het rainingsession.***p<0.001and*p<0.05indicat e st at ist icallysignifi cantdiffer encebet w eenlat enciesont estsessionst ocontr olgr oup anim alsand#

p<0.001indicat esdifferencebet w eenlat enciesont estsessiont o glucosegroup.