Effect of Olanzapine on neuronal activation, parvalbumin-positive interneurons, and parameters of infammation and oxidative stress in rat brain following chronic social isolation

[A. Stanisavljević Ilić]

121 str.

Biologija - Neuronauke / Biology - Neuroscience

Dugotrajna izolacija (IZ) može doprineti razvoju depresije i anksioznosti, pri čemu se kao terapija koristi antipsihotik olanzapin (Olz). Međutim, molekulski mehanizmi delovanja IZ i ograničena efikasnost Olz nisu dovoljno istraženi. Stoga je ispitivan efekat Olz (7,5 mg/kg/dnevno) primenjen tokom poslednje 3 od ukupno 6 nedelja IZ, na ponašanje mužjaka pacova nalik depresivnom i anksioznom. Analizirane su promene u broju c-Fos pozitivnih (c-Fos+) ćelija u moždanim regionima, parvalbumin (PV)+ interneurona i glutamat dekarboksilaze 67 (GAD67)+ ćelija u slojevima (lat. cornu Ammonis, CA 1-3; lat. gyrus dentatus, DG) dorzalnog hipokampusa (dHIP), kao i antioksidativni i anti-inflamacijski efekti Olz u hipokampusu i njegov uticaj na antioksidativni status jetre. Olz je smanjio povećan broj c-Fos+ ćelija u dHIP, retrosplenijalnom i medijalnom prefrontalnom korteksu nakon IZ. Tretman Olz nije uticao na smanjeni broj PV+ ćelija u slojevima stratum oriens (SO) i stratum pyramidale (SP) u dorzalnom CA1 (dCA1) i dDG kod pacova izloženih IZ, ali je povećao broj GAD67+ ćelija u SO i SP slojevima dCA1. U hipokampusu, IZ je povećala proteinsku ekspresiju interleukina-6 (IL-6), supresora signalizacije citokina 3 (SOCS3) i bakar-cink superoksid dismutaze (Cu/Zn-SOD), dok je istu smanjila kod katalaze (KAT). Tretman Olz normalizovao je vrednosti Cu/Zn-SOD i KAT na fiziološki nivo, ali nije uticao na nivo IL-6, dok je smanjio proteinsku ekspresiju SOCS3. U jetri IZ je povećala aktivnost KAT, kao i nivoe malondialdehida i proteinskih karbonilnih grupa, dok je tretman Olz povećao aktivnost SOD i proteinsku ekspresiju Cu/Zn-SOD, a smanjio proteinsku ekspresiju i aktivnost KAT. Dobijeni rezultati doprinose razumevanju mehanizama delovanja IZ i tretmana Olz u moždanim regionima i jetri.

Chronic isolation (CI) can lead to depression and anxiety with antipsychotic drug Olanzapine (Olz) being used as therapy. However, molecular mechanisms of CI and limited efficacy of Olz remain unclear. Therefore, the effect of Olz (7.5 mg/kg/day) administered during the last 3 out of 6-weeks CI was examined in male rats with depression and anxiety-like behaviors. Changes in the number of c-Fos positive (c-Fos+) cells in brain regions, parvalbumin (PV)+ interneurons and glutamate decarboxylase 67 (GAD67)+ cells in layers (cornu Ammonis, CA 1-3; dentate gyrus, DG) of dorsal hippocampus (dHIPP) were analyzed, along with antioxidant and anti-inflammatory effects of Olz in hippocampus, and its impact on antioxidant status of liver. Olz reduced the increased number of c-Fos+ cells in the dHIPP, retrosplenial and medial prefrontal cortex following CI. Olz treatment did not affect the reduced number of PV+ cells in the stratum oriens (SO) and stratum pyramidale (SP) layers of dorsal CA1 (dCA1) and dDG in CI rats, but increased the number of GAD67+ cells in the SO and SP of dCA1. In the hippocampus, CI increased protein expression of interleukin-6 (IL-6), suppressor of cytokine signaling 3 (SOCS3), and copper-zinc superoxide dismutase (Cu/Zn-SOD), while it decreased catalase (CAT) levels. Olz treatment normalized Cu/Zn-SOD and CAT levels to physiological values but didnt affect IL-6 levels and reduced SOCS3 protein expression. In the liver CI increased CAT activity as well as the levels of malondialdehyde and protein carbonyl groups, while Olz treatment increased SOD activity and Cu/Zn-SOD protein expression, and reduced both CAT protein expression and activity. The obtained results contribute to the understanding of mechanisms of CI and Olz treatment in brain regions and liver.

dugotrajna izolacija, ponašanje nalik depresivnom i anksioznom, olanzapin, hipokampus, jetra

Chronic isolation, depression and anxiety-like behaviors, olanzapine, hippocampus, liver

577.25:577.1(043.3)

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