Abst ract
Submitted: December 28, 2015 Accepted: March 31, 2016
Fluoxet ine effect s on periodont ogenesis:
hist om orphom et rical and
im m unohist ochem ical analyses in rat s
Repor t s have indicat ed t hat ser ot onin plays an im por t ant r ole in cell m igrat ion and different iat ion during t he organogenesis of several t issues, including t he oral t y pes. Adm inist rat ion of select ive ser ot onin r eupt ake inhibit or ( SSRI ) drugs during pregnancy could affect t he delivery of serot onin t o em bryonic t issues alt ering it s developm ent . Obj ect ive: This st udy aim ed
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t he form at ion of t he periodont al ligam ent during pregnancy and lact at ion in rat pups. Mat erial and Met hods: Twelve pregnant rat s of Wist ar lineage w ere divided int o four st udy groups. I n t he cont rol group, 0.9% sodium chloride solut ion was adm inist ered orally, t hroughout t he ent ire period of t he 21 days of pregnancy ( CG group) and in t he CGL group, it was adm inist rat ed during pregnancy and lact at ion ( from day 1 of pregnancy t o t he 21st day aft er birt h) . Fluoxet ine was adm inist ered orally at t he dose of 20 m g/ kg in a group t reat ed during pregnancy only ( FG group) , and during pregnancy and lact at ion ( FGL group) . Hist om et rical, hist ochem ical and im m unohist ochem ical
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was m ade under light m icroscopy, and periodont al ligam ent collagen was qualit at ively evaluat ed under a polarizing light m icroscope. Result s: The
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exposure t im e during lact at ion.
Keyw ords: Periodont ium . Fluoxet ine. Serot onin.
Luciana Silva REGUEIRA1
Priscylla Gonçalves
Correia Leite de MARCELOS1
Isabela Maria SANTIAGO-JAEGGER1
Danyel Elias da Cruz PEREZ2
Joaquim EVÊNCIO NETO3
Liriane BARATELLA-EVÊNCIO4
http://dx.doi.org/10.1590/1678-77572015-0564
1Universidade Federal de Pernambuco, Faculdade de Odontologia, Recife, PE, Brasil. 2Universidade Federal de Pernambuco, Faculdade de Odontologia, Departamento de Clínica e Odontologia Preventiva, Seção de Patologia Oral Recife, PE, Brasil.
3Universidade Federal de Pernambuco, Faculdade de Odontologia, Departamento de Morfologia e Fisiologia Animal, Recife, PE.
4Universidade Federal de Pernambuco, Faculdade de Odontologia, Departamento de Histologia e Embriologia, Recife, PE, Brasil.
Corresponding address: Liriane Baratella Evêncio Departamento de Histologia e Embriologia
I nt roduct ion
Th e r e h a v e b e e n a n i n c r e a s i n g n u m b e r o f
p r e scr i p t i o n s f o r a n t i d e p r e ssa n t s si n ce 1 9 9 0 ,
p a r t i cu l a r l y a f t e r t h e i n t r o d u ct i o n o f Se l e ct i v e
Ser ot onin Reupt ak e I nhibit or s ( SSRI s) , w hich ar e
indicat ed in clinical sit uat ions such as depr ession,
obsessive com pulsive and bipolar disorders. I n t his
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pr escr ibed dr u gs f or t h e t r eat m en t of depr essiv e
disor der s, ev en dur ing pr egnancy and lact at ion3 0.
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been report ed in new borns, due t o it s long half- life
and clinically act ive m et abolit es28.
Blood sam ples from t he um bilical cords obt ained
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h av e sh ow n sig n if ican t ser u m lev els, eq u iv alen t
t o 60% of t he m ot her ’s dose11 ZKLFK MXVWL¿HV DQG
pr ov ides suppor t for conduct ing r esear ch w it h t he
aim of det ect ing possible t erat ogenic effect s on babies
exposed t o t his dr ug. Select ive ser ot onin r eupt ake
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in cr eases t h e ex t r acellu lar con cen t r at ion of t h is
neurot ransm it t er, w hich plays im port ant roles in t he
regulat ion of behavior, m ood, anxiet y, aggressiveness,
depression, sleep, fat igue and appet it e suppression6.
Ser ot onin has also been descr ibed as a signal
f o r d ev el o p m en t , d u e t o i t s i n d u ct i v e act i o n i n
t issu e pr olif er at ion an d m or ph ogen esis, n eu r on al
different iat ion, cell m igrat ion, expression of grow t h
fact ors, cellular and ext racellular adhesion19.
A st udy21 invest igat ed t he pat t ern of 5HT recept ors
in t h e d ev elop m en t of r at em b r y os an d v er if ied
m alfor m at ions t hat inv olv ed defect s in t he neural
t ube and front onasal process arising from exposure
t o 5HT ant agonist s. The aut hors concluded t hat t he
use of serot onin ant agonist s m odulat es t he role of
t his neurot ransm it t er in t he m orphogenesis of diverse
craniofacial regions, and could have t he sam e effect
when t hese drugs are adm inist ered during pregnancy.
I n t he sam e st udy, 5HT recept ors w ere det ect ed in
t oot h ger m s and t he m andibular m esenchy m e, in
addit ion t o t he endocar dium , st r iat ed m uscle and
neural crest .
Evidence has show n t he role of serot onin on bone
physiology, since it regulat es ost eoclast different iat ion2,
increases t he quant it y ofost eoprot egerin ( OPG) and
dim inishes t he ost eoclast - act ivat ion fact or RANKL,
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Fur t her m or e, bot h t he ost eoblast s and ost eocy t es
of r at s ar e capable of sy n t h esizin g 5 - HT, as w ell
as ex pr essing funct ional com ponent s of ser ot onin
recept ors and t ransport ers4.
Serot onin has also been report ed t o be a possible
m odulat or of sensorial signals from t he m ast icat ory
m uscles and m echanor ecept or s of t he per iodont al
ligam ent22. The presence of serotonin in the sym pathetic
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t h e r elat ion sh ip of t h is n eu r ot ran sm it t er w it h t h e
m orphogenesis and hom eost asis of oral st ruct ures26.
Since t he serot onin syst em has a regulat ory funct ion
in t he m orphogenet ic processes of neural and
non-neural t issues, including enam el and dent in10 and as
periodont al t issues have been found t o be sensit ive
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drug m ay int erfere in periodont ogenesis.
I n view of t he presence of serot onin absorpt ion
sit es in em bryonic dent al st ruct ures20, t he hypot hesis
of t he int erference of Select ive Serot onin Reupt ake
I nhibit or s on per iodont ium for m at ion is plausible.
How ever, t here are no st udies in t he lit erat ure t hat
have evaluat ed t his hypot hesis. Thus, t he aim of t his
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on t he form at ion of t he periodont ium in rat s w hose
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during pregnancy and lact at ion.
Mat erial and m et hods
Anim als
A r an d om ized , b lin d ex p er im en t al st u d y w as
co n d u ct ed . Th e r esea r ch w a s a p p r o v ed b y t h e
l ocal Et h i cs Com m i ssi on on t h e Use of An i m al s
( prot ocol 23076.017680/ 2011- 83) . The experim ent al
p r oced u r es an d an im al car e w er e in accor d an ce
w it h t he European Convent ion for t he Prot ect ion of
Vert ebrat e Anim als used for Experim ent al and Ot her
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A t ot al of 1 2 r at s (Rat t u s n or v eg icu s alb in u s
Wist ar ) , w it h an av er ag e w eig h t of 2 5 0 g , w er e
random ly divided int o t he st udy groups. The anim als
w ere kept in a room at a t em perat ure of 23 + / - 2° C,
w it h a 12/ 12 hour light / dark cycle ( light from 06: 00
h t o 18: 00 h and dark from 18: 00 h t o 06: 00 hours)
and received t he st andard vivarium diet ( Presence of
rat s and m ice – Presence, Paulínia, São Paulo, Brazil)
and wat er ad libit um. The adult anim als w ere m at ed
pregnancy. The day on w hich pregnancy was proved
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beginning of t he anim als’ t reat m ent s.
Treat m ent
Four groups of 6 pups com prised t he research: t he
cont rol pregnancy group ( CG) , w hich t he pups cam e
from rat s t hat received oral adm inist rat ion of 0.9%
sodium chloride solut ion during t he ent ire period of
pregnancy; cont rol pregnancy and lact at ion group, in
which t he pregnant rat s received oral adm inist rat ion of
0.9% sodium chloride solut ion during pregnancy and
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hy dr ochlor ide ( Phar m a Nost ra, Rio de Janeir o, RJ,
Brazil) dilut ed in saline t o m ake a solut ion w it h a
concent rat ion of 20 m g/ kg/ m ladm inist ered orally up
t o t he end of pregnancy ( FG) , and FGL group, w hich
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t hrough t o t he end of lact at ion, i.e., 21 days aft er
birt h. From each lit t er, t w o m ale pups w ere random ly
select ed, t o com pose t he num ber of six anim als per
st udy group.
At 25 days of life, t he pups of all t he groups w ere
anest het ized by an int ram uscular inj ect ion of ket am ine
hydrochloride ( 50 m g/ kg) and xylazine ( 20 m g/ kg) ,
and were perfused via t he int racardiac rout e wit h a 4%
form aldehyde solut ion. The specim ens w ere obt ained
by m aking a front al cut in t he m axilla at a t angent
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analyze t he periodont ium of t he palat ine root of t he
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Hist olog ical p r ocessin g an d m or p h olog ical
analyses
To charact erize a blind t est , each anim al received
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w ho did not part icipat e in t he analysis process. The
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form aldehyde for 24 hours at room t em perat ure. Aft er
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Fina Lt da, Duque de Caxias, RJ, Brazil) for 15 days.
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t o convent ional hist ological processing for inclusion in
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w er e obt ained and st ained w it h hem at ox y lin- eosin
( HE) , Masson’s Trichrom e ( TM) and picrosirius red, and
m ount ed on Ent ellan® ( Merck Millipore, Darm st adt ,
Hessen, Germ any) .
For collagen analysis, t he hist ological slides st ained
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em it t ed by t he t issue, using a polarizing pet rographic
m icr oscope ( Oly m pus BX40, Oly m pus Cor porat ion,
Tokyo, Honshu, Japan) .
Fo r t h e h i st o m o r p h o m et r i ca l a n a l y si s o f t h e
hist ological sect ions st ained wit h HE, a light m icroscope,
m odel ECLYPSE 51® ( Nikon, Tokyo, Honshu, Japan) ,
was used, coupled t o a m icrocam era, connect ed t o
a com pu t er w it h an im age acqu isit ion car d ( ATI )
an d r u n n in g t h e I MAGE J sof t w ar e p r og r am f or
hist om or phom et r y ( SciJava soft w ar e ecosy st em –
New York, New York, EUA) . From each anim al t en
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ob t ain ed , u sin g a 2 0 X m ag n if icat ion t o m easu r e
t he periodont al ligam ent t hickness and quant ify t he
RVWHREODVWVRVWHRFODVWVFHPHQWREODVWVDQG¿EUREODVWV IRUHDFK¿HOG)RUWKHFHOOFRXQWper¿HOGWKHFHOOV consider ed ost eoblast s w er e t hose adj acent t o t he
ax is parallel t o t he bone m at r ix ; t hose consider ed
ost eoclast s w ere t he m ult inucleat ed, acidophilic cells
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being cells found parallel and adj acent t o cem ent um ,
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I m m u n o h i st o ch em i ca l a n a l y si s o f t y p e I
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To per f or m t h e im m u n oh ist och em ist r y f or t h e
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ant ibody ab34710 was used ( Abcam I nc., Cam bridge,
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neut ral buffer ed parafor m aldehy de ( Sigm a Aldr ich,
São Paulo, SP, Brazil) 4% for 20 hours at 4° C. Aft er
d eh y d r at ion an d d iap h an izat ion b y con v en t ion al
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high grip silanized slides ( EasyPat h, São Paulo, SP,
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t hen ant igen ret rieval was perform ed w it h a sodium
phosphat e buffer solut ion ( PBS) , pH 7.6 in a pressure
cooker for 30 m inut es.
Aft er t his procedure, t he preparat ions were t reat ed
w it h hy dr ogen per ox ide, 3 % solu t ion in absolu t e
m et hanol for 15 m inut es at r oom t em perat ur e t o
b l o ck en d o g en o u s p er ox i d ase. Th en , t h ey w er e
w ash ed in PBS t h r ee t im es f or f iv e m in u t es p er
wash. The areas around t he sect ions on t he slides
w ere cleaned t horoughly and t he prim ary ant ibody
according t o t he m anufact urer ’s prot ocol. They w ere
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each. They sam ples w ere t hen left t o t he addit ion and
UHDFWLRQRIWKH³.LW´1+LVWR¿QH® Sim ple St ain MAX
PO ( MULTI ) ( im m uno- peroxidase Universal polym er,
ant i- m ouse and rabbit - Nichir ei Biosciences I nc.,
Tokyo, Honshu, Japan) . I n each sect ion 2 drops w ere
added t o provide com plet e coverage of t he t issues,
for 30 m inut es at r oom t em perat ur e. Again, t hey
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each. The diam inobenzidine chrom ogen was applied
( DAB - EasyPat h, São Paulo, SP, Brazil) t o preparat ions
t o provide com plet e coverage of t he sect ions for 20
m in u t es at r oom t em perat u r e. Th e sect ion s w er e
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The pr eparat ions w er e count er st ained w it h Har r is
hem at oxylin ( Leica Micr osyst em s, Nussloch,
Rhein-Neckar- Kreiss, Germ any) for 5 m inut es, washed in
wat er, cleared in xylene and m ount ed on Ent ellan®
( Merck Millipore, Darm st adt , Hessen, Germ any) . The
preparat ions were observed and phot ographed under a
light m icroscope, Leica I CC50 HD ( Leica Microsyst em s
Nussloch, Rhein- Neckar- Kreiss Germ any) .
The int ensit y of t he st aining for each ant ibody
w as det er m ined in a sem i- qualit at ive assessm ent .
I m m unor eact iv it y for collagen t y pe I in t he m aj or
t issues and cells in t he periodont ium was charact erized
by a score ( 0, + / - , + , + + , + + + ) . The score ranged
from negat ive st ain ( 0) t o a very st rong posit ive st ain
( + + + ) . A score of + / - represent s t issues/ cells w hich
w ere w eakly posit ive but som e negat ive, a score of +
represent s t issue/ cells w hich w ere posit ive but w it h
w eak st aining and a score of + + represent s t issues/
cells w hich w ere posit ive w it h st rong st aining.
St at ist ics
The quant it at ive dat a w er e t abulat ed using t he
Soft ware program s SPSS 13.0 for Window s and Excel
2 0 0 7 . The Kolm ogor ov- Sm ir nov Test of Nor m alit y
was applied and com par isons bet w een t w o gr oups
w ere m ade using t he Mann- Whit ney U t est , since t he
hypot hesis of norm alit y of t he dat a was excluded. All
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of 95% ( p< 0.05) .
Result s
The rat s had an average of 10 pups per lit t er, but
only t he m ale offspring w ere included in t he st udy
groups. During t he experim ent one FG group puppy
was st illborn.
Hist ological and biochem ical analysis
The hist ological analysis show ed no evidence of
any difference in t he periodont al m orphology bet ween
t he experim ent al groups ( Figure 1) . I n all groups, t he
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wit h approxim at ely half t he root form ed and t he crown
already having erupt ed. At t his st age, t he root apex
was found t o be open and a t hin layer of dent in and
rem ainders of Hert w ig’s epit helial sheat h w ere found
in t his region.
The periodont ium in t he apical region present ed a
large quant it y of undifferent iat ed cells and ost eoclast s,
charact er izing t he phy siological pr ocesses of t oot h
er upt ion. The cer v ical por t ion of t he r oot show ed
a looser per iodont al t issue due t o r em odeling and
r ed i r ect i o n o f t h e p er i o d o n t al f i b er b u n d l es f o r
erupt ion of t he t oot h. Whereas, in t he m iddle port ion
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be m or e m at u r e an d or gan ized, sh ow in g bu n dles
b ei n g i n ser t ed i n t o t h e cem en t u m an d al v eo l ar
bone. Throughout t he ext ension of t he ligam ent , t he
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found adj acent t o t he cem ent um and alveolar bone
surfaces, respect ively. Close t o t he bone, ost eoclast s
w it h norm al m orphology w ere also observed.
I n all gr oups, t he t rabecular alveolar bone was
sh ow n t o be t h in , discon t in u ou s an d w it h am ple
m edullary spaces. Ost eoblast s w ere observed at t he
m argin of t he alveolar bone, as w ell as ost eocyt es
engulfed w it hin t he t rabecular bone, show ing cort ical
b on e in d ev elop m en t . Wit h f u r t h er r ef er en ce t o
t he bone st ruct ures, t he presence of blood vessels
belonging t o t he Haversian syst em was observed in
t he support ing alveolar bone.
Cem ent um deposit ion was observed in t he form of
a t hin, acellular layer, accom panying t he process of
dent inogenesis on root dent in. Cem ent oblast s w ere
show n t o be oval, w it h t he long axis parallel t o t he
root surface.
Bot h t he alveolar bone and cem ent um present ed
a st rong red color in t he hist ological sect ions st ained
w it h picrosirius red. I n t he peripheral port ions of t he
periodont al ligam ent , t he presence of m at ure collagen
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t he ligam ent w ere show n t o be looser and im m at ure,
ev id en ced in Masson ’s Tr ich r om e b y a lig h t b lu e
color ing and in picr osir ius r ed by less int ense r ed
st aining.
Polarizing m icroscopy analysis
The sam ples evaluat ed present ed no alt erat ions
as regards t he t ype and disposit ion of collagen in t he
periodont ium of anim als t hat w ere eit her subm it t ed
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2) . Under polarizing m icroscopy analysis, picrosirius
red showed coherence of periodont al ligam ent collagen
organizat ion in bot h yellow and green colors in bot h
experim ent al groups. The presence of collagen was
also ob ser v ed in t h e b asal lam in a an d acellu lar
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alv eolar b on e p r esen t ed a p r ed om in an ce of r ed
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Th e p o l a r i z a t i o n t e ch n i q u e a l l o w e d f o r t h e
Figure
1-days of life. Control group in Pregnancy (CG), Fluoxetine in Pregnancy (FG), Control in Pregnancy and Lactation (CGL) and Fluoxetine in Pregnancy and Lactation (FGL). Images stained with hematoxylin and eosin, Masson’s Trichrome and picrosirius red. Note the cells that
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bundles, which were disposed obliquely and ascending
in t he cem ent - alveolar bone direct ion.
Hist om orphom et ric analysis
Th e m e a s u r e m e n t s p e r f o r m e d r e v e a l e d n o
st at ist ical difference bet w een t he CG and FG groups,
for any of t he analyzed variables ( Table 1) .
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Variables Group CG Group FG p-Value*
Mean + SD Mean + SD
Periodontal Ligament thickness 290.17i ± 26.68i 287.03 ± 21.45 0.447
Fibroblast 57.35 ± 13.86 61.88 ± 9.66 0.091
Osteoblast 8.28 ± 2.69 7.23 ± 2.23 0.081
Osteoclast 0.67 ± 0.77 0.45 ± 0.65 0.105
Cementoblast 9.15 ± 2.91 10.23 ± 2.81 0.073
(i) inches
Table 1- Evaluation of periodontal ligament thickness and quantity of periodontium cell type in Groups CG and FG
Figure
2-days of life. Control group in Pregnancy (CG), Fluoxetine in Pregnancy (FG), Control in Pregnancy and Lactation (CGL) and Fluoxetine in Pregnancy and Lactation (FGL). Cuts stained with picrosirius red and analyzed under a polarizing microscope. Note the predominance
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in t he num ber of cells of w hich t he per iodont ium
is com posed. The FGL group show ed a st at ist ically
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( p= 0.006) , ost eoblast s ( p= 0.027) and cem ent oblast s
( p= 0.001) w hen com pared w it h it s respect ive cont rol
g r ou p ( CGL) . Th e m easu r em en t s of p er iod on t al
ligam ent t hickness and quant it y of ost eoclast bet ween
t h e CGL an d FGL g r ou p s sh ow ed n o st at ist ically
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I m m unohist ochem ical analysis of collagen I
Type I collagen im m unoreact ivit y was evident by a
very st rong posit ive st ain ( + + + ) in t he alveolar bone
and dent in in all gr oups. The per iodont al ligam ent
show ed a posit ive but w eak st aining in all specim ens
( Figure 3) .
Discussion
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relat ive t o t he st age of t oot h developm ent and t he
m orphology of st ruct ures present in t he periodont ium
of t he anim als w ere in conform it y w it h t he descript ion
of t h e r at p er iod on t iu m in p r ev iou s st u d ies t h u s
conferring a pat t ern of m orphological norm alit y in t he
experim ent al groups1.
Th e h ist om or p h om et r ical an aly sis r ev ealed a
VLJQL¿FDQWUHGXFWLRQLQWKHQXPEHURIFHPHQWREODVWV RVWHREODVWV DQG ¿EUREODVWV LQ WKH SHULRGRQWLXP RI
pups from t he FGL group, w hose m ot hers received
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t her e w er e no alt erat ions in t he gr oup of anim als
H[SRVHG WR ÀXR[HWLQH GXULQJ SUHJQDQF\ RQO\ )*
group) .
I t has been report ed t hat t he effect s of t he use
RIÀXR[HWLQHGXULQJODFWDWLRQFDQEHWUDQVPLWWHGWR
Figure 3- Control group – Periodontal ligament presenting moderate positivity for collagen type I. Bar equivalent to 123 μm
Variables Group CGL Group FGL p-Value*
Mean + SD Mean + SD
Periodontal Ligament thickness 287.21i ± 29.63i 294.04 ± 37.93 0.445
Fibroblast 58.68 ± 13.98 51.68 ± 11.66 0.006
Osteoblast 7.30 ± 2.47 6.33 ± 2.43 0.027
Osteoclast 0.40 ± 0.56 0.32 ± 0.57 0.292
Cementoblast 10.95 ± 2.09 9.75 ± 2.49 0.001
(i) inches
t he new born257KHFOHDUDQFHRIÀXR[HWLQHGHFUHDVHV
LQ WKH SRVWSDUWXP SHULRG DQG ÀXR[HWLQH VHUXP LQ
t he m ot her is higher in t his period t han in t he t hird
t r im est er of pr egnancy1 8, w hich could ex plain t he
¿EUREODVWFHPHQWREODVWDQGRVWHREODVWUHGXFWLRQLQ
t he periodont al ligam ent in only t he FGL group.
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cells of t he periodont ium has not been report ed in t he
lit erat ure, som e st udies have reinforced t he foundat ion
for t his hypot hesis. The t oot h follicle, responsible for
t he form at ion of t he periodont ium , is derived from
t he neural crest cells27. Serot onin is responsible for
regulat ing cell m igrat ion from t he neural crest during
neurulat ion in a dose- dependent m anner23. Therefore,
t he effect s of select ive serot onin reupt ake m ay affect
st r uct ur es such as t he per iodont ium , der ived fr om
t his annex.
St u dies pr ev iou sly con du ct ed by ou r r esear ch
group did not reveal alt erat ions in t he form at ion and
m or phology of t he t em por om andibular j oint ( TMJ)7
DQGWRRWKHQDPHORIUDWSXSVWUHDWHGZLWKÀXR[HWLQH
( 10 m g/ k g) dur ing pr egnancy29. Never t heless, t he
DGPLQLVWUDWLRQ RI PJNJ ÀXR[HWLQH GXULQJ UDW SUHJQDQF\DQGODFWDWLRQPRGL¿HGWKHMDZERQHPDVV
of t he pups8. Taking t hese result s int o considerat ion,
besides t he fact t hat t he dose m ost used in hum ans
is 20 m g/ kg, w e opt ed t o conduct our st udy using t he
20 m g/ kg dose. The alt erat ions det ect ed at t he dose
of 20 m g/ kg can be explained by t he possibilit y of
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dose- dependent pat t ern described by Moiseiwit sch and
Lauder24 ( 1996) when t hey analyzed t he developm ent
of t he t oot h germ in vit r o.
Hodge, et al.15 ( 2012) dem onstrated the involvem ent
RIÀXR[HWLQHLQERQHPHWDEROLVPLQDQin vit r o st udy. Th e au t h or s d et ect ed t h at b ot h ost eob last s an d
ost eoclast s, in addit ion t o expressing t he serot onin
t r an sp o r t er ( 5 - HTT) an d t h e ser o t o n i n r ecep t o r
5- HTR1B, also present ed t rypt ophan hydroxylase, an
enzym e t hat cat alyzes t rypt ophan for t he form at ion of
VHURWRQLQ,QWKLVVDPHVWXG\ÀXR[HWLQHZDVVKRZQ
t o inhibit t he quant it y of ost eoclast s and resorpt ion, in
DGRVHGHSHQGHQWPDQQHU$WDKLJKGRVHÀXR[HWLQH
also inhibit ed m ineralizat ion by t he ost eoblast s, but did
not alt er t he m orphological param et er of t he cells in
FXOWXUH:KHUHDVLQWKHSUHVHQWVWXG\QRVLJQL¿FDQW
alt erat ions w ere found in t he num ber of ost eoclast s.
Th er e i s co n v i n ci n g ev i d en ce t h a t ser o t o n i n
m odulat ors such as SSRI s can affect bone t urnover
d u e t o t h e cap acit y of t h e 5 - HT2 BR r ecep t or t o
facilit at e ost eoblast recruit m ent and proliferat ion9,13.
:LWK UHJDUGV WR ¿EUREODVWV LW KDV EHHQ HVWDEOLVKHG
t hat t hese cells express chains of int ercellular signals
act ivat ed by t he serot onin recept or 5HTlc16. There are
no st udies t hat correlat e t he effect s of serot onin and
it s inhibit or s on cem ent oblast s. How ever, as t hese
cells or iginat e fr om t he sam e em br yonic t issue as
¿EUREODVWV DQG RVWHREODVWV WKH WRRWK IROOLFOH LW LV
suggest ed t hat t hese cells are m odulat ed in a sim ilar
m anner by serot onergic st im uli.
Type I collagen is t he largest com ponent of t he
p er iod on t al lig am en t1 7. Pr ocollag en an d t y p e I I I
collagen are com ponent s of t he periodont al ligam ent
¿EHUEXQGOHVDQGWKHLUFRORFDWLRQZLWKW\SH,FROODJHQ
i n t h e sa m e f i b er h a s b een su g g est ed3. I n t h e
SUHVHQW VWXG\ WKH W\SHV RI FROODJHQ ¿EHUV IRXQG LQ
t he periodont al ligam ent did not present differences
bet w een bot h ex per im ent al gr oups obser ved under
im m unohist ochem ical analyses, w hat is in conform it y
w it h t he descript ion of t he periodont ium report ed in
t he lit erat ure12.
Conclusion
The result s obt ained suggest ed t hat periodont al
FHOOVDUHVHQVLWLYHWRWKHDFWLRQRIÀXR[HWLQHDQGLW
appears t o be dependent on t he t im e of exposure,
since only t he group exposed during pregnancy and
lact at ion p r esen t ed a d ecr ease in t h e q u an t it ies
o f f i b r o b l a st s, ce m e n t o b l a st s a n d o st e o b l a st s.
Despit e t h e cell r edu ct ion in t h e FGL gr ou p, t h e
d e scr i p t i v e m o r p h o l o g i ca l a n a l y si s sh o w e d n o
st ruct ural periodont al changes, so furt her st udies m ust
EHFRQGXFWHGWRFRQ¿UPWKHLQYROYHPHQWRIÀXR[HWLQH
on periodont ogenesis.
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