A new animal model of (chronic) depression induced by repeated and intermittent lipopolysaccharide administration for 4 months
PBN-AR
Instytucja
Instytut Farmakologii im. Jerzego Maja Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
en
Czasopismo
BRAIN BEHAVIOR AND IMMUNITY
ISSN
0889-1591
EISSN
1090-2139
Wydawca
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI
URL
Rok publikacji
2013
Numer zeszytu
Strony od-do
96-104
Numer tomu
31
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
en
Chronic depression;
Inflammation;
Cytokines;
Leaky gut;
LPS;
Oxidative and nitrosative stress
Streszczenia
Język
en
Treść
Chronic activation of immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways plays an important role in the pathophysiology of clinical depression. Increased IgA responses directed against LPS of gram-negative bacteria, indicating increased bacterial translocation, may be one of the drivers underpinning these pathways. There is a strong association between signs of bacterial translocation and chronicity of depression and O&NS, but not pro-inflammatory cytokines.The aims of the present study were to: (1) develop a new neurobehavioral model of (chronic) depression (anhedonic behavior) that may reflect chronic LPS stimulation and is associated with increased oxidative stress, and (2) to delineate the effects of fluoxetine on this new depression model.We established that in female mice repeated LPS injections once daily for 5days (from 750μg/kg to a maximal dose 1250μg/kg; increasing doses for the first three days which were then gradually decreased on day 4 and 5) at a one-month interval and this repeated for 4 consecutive months induced chronic anhedonia (estimated by the preference to drink a 1% sucrose) lasting for at least 7weeks. Chronic LPS administration significantly decreased thymus weight, proliferative activity of splenocytes, production of interferon (IFN)γ and interleukin-(IL)10, and increased superoxide and corticosterone production. Treatment with fluoxetine for 3weeks abolished the neurobehavioral effects of LPS. The antidepressant effect of fluoxetine was accompanied by increased production of IL-10 and reduced superoxide and corticosterone production.Our results suggest that repeated intermittent LPS injections to female mice may be a useful model of chronic depression and in particular for the depressogenic effects of long standing activation of the toll-like receptor IV complex.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
480334
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