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Previous issue date: 2017-03-15 / A depress?o reduz a qualidade de vida do indiv?duo, compromete a funcionalidade
profissional e social e ? considerada a principal causa para incapacidade em termos de
anos perdidos no curso da doen?a. Apesar da severidade relatada, ainda n?o h? uma
compreens?o clara dos substratos neurais alterados na depress?o, por isso o estudo de
modelos animais que investiguem a etiologia deste transtorno torna-se extremamente
necess?rio. Este trabalho buscou comparar altera??es bioqu?micas no soro, c?rtex pr?frontal
(CPF) e hipocampo de camundongos submetidos a dois modelos animais de
depress?o: desamparo aprendido e administra??o do lipopolissacar?deo de E.Coli (LPS).
O teste de desamparo aprendido resultou em m?dia 70 % de animais desamparados,
verificado pela falha em escapar aos choques 24 h e 48 h ap?s a sess?o de indu??o do
desamparo. Os 30 % restantes foram considerados resilientes. Os animais desamparados
apresentaram mais dano oxidativo no CPF e soro, quando comparados aos animais
controles. N?o houve diferen?a entre desamparados e resilientes, por?m, foi observada
correla??o positiva entre o dano oxidativo no soro e CPF e o comportamento
desamparado. A concentra??o das citocinas pr?-inflamat?rias IL-1?, TNF?, IL-6 e antiinflamat?ria
IL-10 no CPF e hipocampo dos animais submetidos ao desamparo e
controles n?o foi diferente entre os grupos, por?m houve correla??o positiva entre a
citocina IL-6 no hipocampo e o comportamento desamparado dos animais. A atividade
da enzima indolamina 2,3-dioxigenase (IDO) n?o apresentou diferen?a significativa nos
animais submetidos ao modelo do desamparo e controles. A administra??o sist?mica de
LPS (0,8 mg/kg i.p.) induziu um comportamento doentio nos animais, caracterizado por
diminui??o da ingest?o de ?gua e comida, perda de peso e altera??o da temperatura retal
6 h ap?s a inje??o. Em 24 h o estado doentio diminuiu, por?m, os animais que
receberam LPS apresentaram imobilidade aumentada no teste de suspens?o pela cauda
em compara??o aos animais que receberam salina. Foi observado mais dano oxidativo
no soro, CPF e hipocampo do grupo LPS em compara??o aos grupos salina e controle.
As citocinas IL-?, TNF? no soro, CPF e hipocampo n?o apresentaram nenhuma
altera??o, indicando que a inflama??o induzida pela administra??o de LPS foi transit?ria.
A citocina IL-6 mostrou-se elevada no CPF do grupo que recebeu LPS em compara??o
ao grupo salina, correlacionada positivamente com o comportamento do tipo depressivo
dos animais. Os n?veis de IL-10 no hipocampo correlacionaram-se negativamente com o
comportamento do tipo depressivo e a atividade da IDO foi aumentada no CPF e
diminu?da no hipocampo do grupo LPS. Os resultados apresentados corroboram a
hip?tese da ativa??o do sistema imune no evento depressivo e consequente dano
oxidativo, verificado em dois modelos animais de depress?o. A ativa??o da IDO variou
entre as ?reas analisadas em cada modelo animal. / Major depression has a great impact on an individual?s quality of life and it is
considered the leading cause of burden in terms of years lost due to disability. However,
despite the severity of depression, the pathophysiology of the disease is still elusive. In
this regard, the use of animal models plays an important role in research for the etiology
of depression. This work compared biochemical alterations occurring on serum, prefrontal
cortex (PFC) and hippocampus in two animal models of depression: learned
helplessness and administration of lipopolyssaccharide from E.Coli (LPS). Learned
helplessness protocol used in this work resulted in 70 % of helpless mice, assessed by
the inability to escape from electroshocks given 24 h or 48 h after the helpless-induction
session. The other 30 % of mice were considered resilient. Helpless animals showed
more oxidative damage in PFC and serum when compared to controls. No difference
was seen between helpless and resilient groups, but there was a positive correlation
between the oxidative damage on serum and PFC and helpless behavior. There was no
difference in the concentration of IL-1?, TNF?, IL-6 and IL-10 cytokines on PFC and
hippocampus of the animals exposed to the learned helplessness test, but there was a
significant positive correlation between IL-6 concentration and depressive-like behavior
on hippocampus. Indoleamine 2,3-dioxygenase (IDO) enzyme activity was not altered
on learned helplessness model. Systemic administration of LPS (0,8 mg/kg) induced
sickness behavior on animals characterized by decreased food and water intake, bodyweight
loss and altered body temperature 6 h after administration. Sickness behavior is
over after 24 h, but LPS-treated mice displayed higher immobility time in the tail
suspension test when compared to saline. There was more oxidative damage in serum,
PFC and hippocampus of LPS group when compared to saline and controls. No
differences on IL-1? and TNF? concentration on serum, PFC and hippocampus of the
animals were detected, suggesting a transient nature of the LPS-induced inflammation.
LPS-treated group displayed higher concentrations of IL-6 on PFC when compared to
saline group, and IL-6 concentration positively correlated to depressive-like behavior.
IL-10 concentrations on hippocampus were negatively correlated to depressive-like
behavior and IDO activity was increased on PFC and decreased on hippocampus of
LPS-treated mice. Data presented here corroborate for the hypothesis of immune
activation during depressive episodes, then resulting in oxidative damage assessed in
two animal models of depression. IDO activity behaved with some specificity in each
animal model depending on the brain or systemic area.
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/23651 |
| Date | 15 March 2017 |
| Creators | Didonet, Julia Jensen |
| Contributors | 97013390968, http://lattes.cnpq.br/1759328747578795, Silva, Alianda Maira Cornelio da, 01179848683, Soares, Bruno Lob?o, 07069406797, http://lattes.cnpq.br/3124118595692286, Gaspar, Danielle Macedo, 50160176387, http://lattes.cnpq.br/1566937332957369, Silva, Regina Helena da, 18747270829, http://lattes.cnpq.br/0101190051087933, Gavioli, Elaine Cristina |
| Publisher | PROGRAMA DE P?S-GRADUA??O EM PSICOBIOLOGIA, UFRN, Brasil |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/doctoralThesis |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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