Glibenclamide treatment modulates the expression and localization of myosin-IIB in diabetic rat brain

Costa, Alice Vieira da; Calábria, Luciana Karen; Santos, Paula de Souza; Goulart, Luiz Ricardo; Espíndola, Foued Salmen

doi:10.1016/j.jns.2014.03.020

Cited by 3 publications

(3 citation statements)

References 63 publications

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“…Glyburide has been shown to improve high fat diet-induced anxiety and cognitive impairment [27] and reduce the expression of myosin-IIB in the frontal cortex and hippocampus of diabetic rats [28] . In our study glibenclamide treatment partially reversed cognitive impairment in diabetic rat thus confirming the cognitive impairment in these animals to be mediated by T2D [29] .…”

Section: Resultssupporting

confidence: 85%

Characterization of Cognitive Impairment in Type 2 Diabetic Rats

Mehta¹,

Banerjee²

2017

pharmaceutical-sciences

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Among all the secondary complications of type 2 diabetes, cognitive impairment associated with diabetes is less well studied and characterized. We made an attempt to investigate the molecular mechanisms involved in cognitive decline in high fat diet-streptozotocin model of type 2 diabetes. High-fat diet and a single low dose streptozotocin (25 mg/kg) were used to induce diabetes in Sprague-Dawley rats. Developments of cognitive deficit in these animals were measured using change in transfer latency in elevated plus maze test and stepdown latency in passive avoidance test. This was followed by biochemical estimation of acetylcholinesterase and reduced glutathione levels followed by histological evaluation of cortical and hippocampal slices. The high fat diet-streptozotocin animals developed type 2 diabetes, characterized by an increase in fasting blood glucose levels >250 mg/kg, marked increase (P<0.001) in triglyceride (207±7.2) and total cholesterol level (125.3±2.7) with a decrease (P<0.001) in high-density lipoproteins (14.27±1.1) when compared to control animals. After 4 weeks of development of type 2 diabetes high fat diet-streptozotocin animals showed signs of cognitive deficit with a significant decline in step-down latency (P<0.001) and a significant increase in transfer latency (P<0.001) compared to controls. The high fat diet-streptozotocin animals also showed significant decrease (P<0.001) in cortico-hippocampal glutathione levels and increase in (P<0.001) acetylcholinesterase activity as compared to control animals suggesting type 2 diabetes-associated oxidative stress and decrease in hippocampal Ach activity. Immunohistochemical studies in these animals showed pronounced astrogliosis and microglial activation in the cortical and hippocampal slices suggesting neuroinflammatory changes. We also found significant loss (P<0.001) of hippocampal neurons at CA1 and CA3 region in the diabetic rats as compared with healthy controls. Antidiabetic compound glibenclamide (10 mg/kg for 3 weeks) partly reversed the above neurobehavioral, biochemical and histological changes in the diabetic rat brain. Hence we show that high fat diet-streptozotocin type 2 diabetic rats may develop signs of cognitive impairment. This cognitive decline was found to be associated with an increase in acetylcholinesterase activity and loss of hippocampal neurons. Oxidative stress and neuroinflammatory changes in the brain of these animals may be responsible for hippocampal neuronal loss, which could be partly reversed upon glibenclamide treatment.

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Section: Resultssupporting

confidence: 85%

Characterization of Cognitive Impairment in Type 2 Diabetic Rats

Mehta¹,

Banerjee²

2017

pharmaceutical-sciences

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“…Glibenclamide also reverse damage caused by diabetes on myosin-IIB expression and reduce the patho-physiological changes in the brain. 20 Myosin-Va distribution in non-diabetic is more intense in the cytoplasmic soma and extension of pyramidal neurons with intense perinuclear labeling in both cortex (Figure 3A-D; Figure 5A-D), a similar pattern was described by Takagishi et al 47 . Myosin-Va is a molecular motor associated with transport vesicles in neurons 48 and its expression changed after treatment with aqueous Pouteria ramiflora extract, likely as a response to the plant's antioxidant and neuroprotective properties.…”

Section: Resultssupporting

confidence: 80%

“…The rats were fasted for 24 h, anesthetized by intraperitoneal injection of xylazine (10 mg/kg body weight, bw)/ketamine (75 mg/ kg bw) and streptozotocin (40 mg/kg bw, 0.01 M citrate buffer, pH 4.5; Sigma-Aldrich, USA) via the penile vein (2 mL/kg bw) was injected. 6,8,9,20,21 Non-diabetic rats received equal volume of citrate buffer through penile vein. Then animals were fasted for another 90 min after injection.…”

Section: Induction Of Diabetes Mellitusmentioning

confidence: 99%

Vochysia rufa and glibenclamide promote effects on oxidative damage and in proteins implicated in vesicular trafficking in diabetic rat brain

Costa¹,

Calábria²,

Rezende³

et al. 2022

OAJS

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Many Vochysiaceae species are widely used in folk medicine to treat some diseases. Vochysia rufa, popularly known as “quina-doce”, has been used in folk medicine to treat type 1 and type 2 diabetes mellitus in the state of Minas Gerais, Brazil. Although the antidiabetic and antioxidant effects and phytochemical profile of Vochysia rufa have already been elucidated, further studies are needed on the effects of this treatment in specific tissues, such as the brain. This study investigated the effect of aqueous extract of Vochysia rufa in diabetic rat brains and for this purpose, oxidative stress markers and the expression/localization of proteins implicated in vesicular trafficking were evaluated. Thirty-two rats were randomized into four groups (non-diabetic, diabetic non-treated, diabetic treated for 43 days with glibenclamide - 6 mg/kg or Vochysia rufa - 500 mg/kg). The extract was administered by gavage for 43 days. Analyses were conducted of enzymes concentration and activity in the brain. The protein levels and localization of myosin-Va, CaMKII, synapsin, SNAP-25 and GLUT4 were also analyzed. Vochysia rufa extract decreased superoxide dismutase, glutathione peroxidase, reduced glutathione, total sulfhydryl and lipid peroxidation levels and increased glutathione S-transferase levels. Additionally, Vochysia rufa treatment increased the expression of myosin-Va, CaMKII and also synapsin, which were confirmed by immunolocalization. The treatment with aqueous extract of Vochysia rufa reduces oxidative stress on diabetic rat and protecting the brain from damage caused by hyperglycemia.

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