جستجوی مقالات مرتبط با کلیدواژه « Dorsal hippocampus » در نشریات گروه « پزشکی »

Studies have shown that polycystic ovary (PCO) may be induced by morphine and CA1 may be damaged by PCO-related oxidative stress but can be protected by a potent GABAB receptor agonist. Therefore, this study aimed to investigate the protective effect of baclofen against oxidative stress in the dorsal hippocampus (DH) of morphine-treated rats with ovarian cysts.

 In total, 66 female Wistar rats were selected and randomly divided into control and experimental groups. The control group received saline (1 ml/kg, intraperitoneally [i.p.], once a day). Experimental groups were treated with morphine (5 mg/kg, i.p.), baclofen alone (10-30 mg/kg, i.p.), and baclofen (10, 20, 30 mg/kg, i.p.) before morphine (5 mg/kg, i.p.), once daily. One group received morphine (0.4 µg/rat) once in the ventromedial hypothalamus, and the last ovariectomized group was administered morphine (5 mg/kg, i.p.) after recovery. Then blood and hippocampus samples were prepared. Moreover, the levels of oxidative stress factors (GPX, MDA, SOD, and CAT), and the intensity of estrogen and glucocorticoid receptors in DH were evaluated. Ovaries and the uterus were also examined biometrically.

In the morphine-treated groups, regardless of the injection method, the development of follicles was rare, compared to the control group, instead, thick-walled follicular cysts were abundant. However, in the groups that received baclofen alone or baclofen together with morphine, the number of cysts decreased and the number of mature follicles increased significantly. Oxidative agents showed high levels in the DH of the morphine-treated group, which correlated with low estrogen receptors in DH. However, baclofen pretreatment improved these conditions. Besides, glucocorticoid receptors in DH did not show significant differences in different groups, and necrosis in the CA1 area was not observed either in the morphine-receiving group or in the other groups. The uterus did not show significant changes in any group.

Prophylactic use of baclofen can protect against morphine side effects.

Mitochondria and peroxisomes are tightly connected organelles that cooperate in lipid oxidation and maintenance of redox homeostasis. However, the peroxisome’s role in the modulation of the mitochondrial regulatory factors has remained unanswered. SIRT1- PGC-1α interaction as a pivotal pathway in energy expenditure leads to mitochondrial biogenesis. Histone deacetylase (HDAC)6 and HDAC10 also regulate mitochondrial dynamics. Mitochondrial dysfunction is a cause and/or consequence of aging and neurodegenerative disorders.

In this study, to disturb importing proteins into the peroxisomes, PEX5 was down-regulated in the dorsal hippocampus by lentivirus-mediated shRNA. The impact of PEX5 reduction on peroxisomes was explored by assessment of catalase activity, a regular peroxisome matrix enzyme, and PMP70 and PEX14 expression. Then, mitochondrial biogenesis factors, PGC-1α, and mitochondrial transcription factor A (TFAM) were measured by quantitative polymerase chain reaction and mitochondrial-related HDACs, SIRT1, SIRT3, HDAC6 and HDAC10, by western blotting. Besides, spatial learning and memory were assessed using the Morris water maze task.

Our results revealed a significant reduction of HDAC6 and SIRT1, alongside with decrease in mitochondrial biogenesis factors PGC-1α and TFAM, and no alteration in HDAC10 and SIRT3. Despite all observed changes, memory performance displayed no detectable alteration in the experimental groups. These data suggest the role of peroxisomes in modulating mitochondrial dynamics via regulation of HDAC6 and SIRT1 expression.

Peroxisome dysfunctions may occur upstream to mitochondrial failure and can be considered as a potential therapeutic target for aging and age-related disorders.