Changes in Cyclooxygenase-2 Immunoreactivity in the Hippocampus in a Model of Streptozotocin-Induced Type 1 Diabetic Rats

Nam, Sung Min; Yi, Sun Shin; Yoo, Dae Young; Kim, Woosuk; Choi, Jung Hoon; Hwang, In Koo; Seong, Je Kyung; Yoon, Yeo Sung

doi:10.1292/jvms.12-0036

Cited by 5 publications

(5 citation statements)

References 34 publications

(43 reference statements)

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“…However, the COX-2 pathway is not essential for the promotion of neuronal maturation following treatment with AA extract. Although multiple studies have reported that COX-2 has a pivotal role in enhancing neurogenesis in the hippocampus [131415], our western blot results showed that COX-2 expression in the hippocampus did not significantly change with chronic AA administration in mice fed either of the diets. It may be that AA does not affect the COX-2-related pathways, but that an alternative signaling pathway enhances neurogenesis.…”

Section: Discussioncontrasting

confidence: 68%

Neuronal maturation in the hippocampal dentate gyrus via chronic oral administration ofArtemisa annuaextract is independent of cyclooxygenase 2 signaling pathway in diet-induced obesity mouse model

et al. 2017

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Recently, we reported that Artemisia annua (AA) has anti-adipogenic properties in vitro and in vivo. Reduction of adipogenesis by AA treatment may dampen systemic inflammation and protect neurons from cytokine-induced damage. Therefore, the present study was undertaken to assess whether AA increases neuronal maturation by reducing inflammatory responses, such as those mediated by cyclooxygenase 2 (COX-2). Mice were fed normal chow or a high-fat diet with or without chronic daily oral administration of AA extract (0.2 g/10 mL/kg) for 4 weeks; then, changes in their hippocampal dentate gyri were measured via immunohistochemistry/immunofluorescence staining for bromodexoxyuridine, doublecortin, and neuronal nuclei, markers of neuronal maturation, and quantitative western blotting for COX-2 and Iba-1, in order to assess correlations between systemic inflammation (interleukin-6) and food type. Additionally, we tested the effect of AA in an Alzheimer's disease model of Caenorhabditis elegans and uncovered a potential benefit. The results show that chronic AA dosing significantly increases neuronal maturation, particularly in the high-fat diet group. This effect was seen in the absence of any changes in COX-2 levels in mice given the same type of food, pointing to the possibility of alternate anti-inflammatory pathways in the stimulation of neurogenesis and neuro-maturation in a background of obesity.

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Section: Discussioncontrasting

confidence: 68%

Neuronal maturation in the hippocampal dentate gyrus via chronic oral administration ofArtemisa annuaextract is independent of cyclooxygenase 2 signaling pathway in diet-induced obesity mouse model

et al. 2017

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“…In addition, treadmill exercise in COX-2 knockout mice significantly increased neurogenesis in the dentate gyrus ( 28 ). With colleagues, we have also demonstrated that COX-2 immunoreactivity was significantly increased in the hippocampus 3 weeks after streptozotocin treatment ( 29 ), while cell proliferation and neuroblast differentiation were significantly decreased at 3 weeks after streptozotocin treatment ( 30 ). The induction of COX-2 subsequently increases the synthesis of prostaglandin E 2 (PGE 2 ).…”

Section: Discussionmentioning

confidence: 83%

Hypothyroidism increases cyclooxygenase-2 levels and pro-inflammatory response and decreases cell proliferation and neuroblast differentiation in the hippocampus

et al. 2018

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The present study investigated the effects of hypothyroidism on cyclooxygenase-2 (COX-2) and pro-inflammatory cytokines in the dentate gyrus to elucidate the roles of COX-2 in the hypothyroid hippocampus. Hypothyroidism was induced in rats by treating with 0.03% 2-mercapto-1-methyl-imidazole dissolved in drinking water for 5 weeks. The animals were sacrificed at 12 weeks of age. Hypothyroidism rats exhibited decreased triiodothyronine and thyroxine levels in the serum, while the levels of thyroid-stimulating hormone and the weight of thyroid glands were significantly higher in the hypothyroid rats compared with those in the vehicle-treated group. COX-2 immunoreactivity was significantly increased in the hippocampal CA2/3 region and the dentate gyrus compared with the vehicle-treated group. Levels of pro-inflammatory cytokines including interleukin (IL)-1β, IL-6 and tumor necrosis factor-α were significantly higher in the hippocampal homogenates of hypothyroid rats. Cell proliferation and neuroblast differentiation based on Ki67 and doublecortin immunohistochemistry were decreased in the dentate gyrus of hypothyroid rats compared with those in the vehicle-treated group. These results suggested that hypothyroidism-mediated COX-2 expression affected hippocampal plasticity by upregulating the levels of pro-inflammatory cytokines in the hippocampus. Therefore, COX-2 may be suggested as a candidate molecule for preventing hypothyroidism-induced neurological side effects.

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“…Rats were randomly assigned to the following groups ( n = 8 per group): control (Con), sevoflurane (Sev), DM (DM), DM + sevoflurane (DM/Sev), DM + sevoflurane + celastrol (Cel). In the 3 diabetes groups (DM, DM/Sev, and Cel), rats were given intraperitoneal injections of 10% STZ (1 mg/ml; S0130; Sigma, USA) in citrate buffer at 60 mg/kg to induce DM [ 9 , 10 ]. The preparation and injection of STZ were done under aseptic conditions.…”

Section: Methodsmentioning

confidence: 99%

“…If the time allowed to elapse before beginning the inhalation procedure is too long, some diabetic rats may die of unknown causes or die during the exposure to sevoflurane. For these reasons and on the basis of findings from pilot study data reported by others [ 9 , 11 ], we began the inhalation procedure 20 days after intraperitoneal (IP) injection of STZ.…”

Section: Methodsmentioning

confidence: 99%

The effect of celastrol on learning and memory in diabetic rats after sevoflurane inhalation

Liao¹,

Xiao²,

Zhu³

et al. 2018

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IntroductionThe aim was to devise an animal model showing some of the neuropathological changes seen in senile dementia, and to investigate the effect of celastrol on cognition neuropathology in this model.Material and methodsForty male Sprague Dawley rats weighing 300–350 g were randomly divided into 5 groups (n = 8 each): control (Con); inhaled sevoflurane (Sev); diabetes mellitus (DM); diabetes mellitus + inhaled sevoflurane (DM/Sev); diabetes + inhaled sevoflurane + celastrol (Cel). Diabetes was induced by an intraperitoneal injection of streptozotocin (STZ). After 20 days, the Sev, DM/Sev and Cel group rats inhaled 3% sevoflurane for 2 h, while the control and DM groups inhaled air. Cel group rats were given intraperitoneal injections of celastrol (0.7 mg/kg) daily for 4 days, while the control group received intraperitoneal injections of an equal volume of dimethylsulfoxide. The Morris water maze test was performed to test cognition. Animals were killed after the last water maze test and Congo red staining was used to observe deposition of amyloid substance in the hippocampus. The expression of GFAP and IGF-1 in the hippocampus was observed by immunohistochemistry.ResultsDiabetes decreased cognition, increased amyloid substance and GFAP expression, and decreased IGF-1 expression in the hippocampus (all p-values < 0.05). Sevoflurane administration intensified and celastrol decreased these changes (all p-values < 0.05).ConclusionsSev/DM rats showed cognitive and neurochemical changes similar to those seen in senile dementia. Celastrol decreased these changes and should be evaluated further as a possible clinical agent in dementia.

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Changes in Cyclooxygenase-2 Immunoreactivity in the Hippocampus in a Model of Streptozotocin-Induced Type 1 Diabetic Rats

Cited by 5 publications

References 34 publications

Neuronal maturation in the hippocampal dentate gyrus via chronic oral administration ofArtemisa annuaextract is independent of cyclooxygenase 2 signaling pathway in diet-induced obesity mouse model

Neuronal maturation in the hippocampal dentate gyrus via chronic oral administration ofArtemisa annuaextract is independent of cyclooxygenase 2 signaling pathway in diet-induced obesity mouse model

Hypothyroidism increases cyclooxygenase-2 levels and pro-inflammatory response and decreases cell proliferation and neuroblast differentiation in the hippocampus

The effect of celastrol on learning and memory in diabetic rats after sevoflurane inhalation

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