Alteration of Aquaporins 1 and 4 immunohistochemical and gene expression in the cerebellum of diabetic albino rat.

Aquaporins (AQPs) are a family of transmembrane channel proteins. AQP1 and AQP4 are expressed in cerebellum amongst others. This study was designed to assess the effect of diabetes on AQP1 and AQP4 expression in cerebellum of rats. Diabetes was induced by a single intraperitoneal injection of Streptozotocin 45 mg/kg in 24 adult male Sprague Dawley rats. Six rats from control and diabetic groups were sacrificed at one, four, and eight weeks post diabetic confirmation. After eight weeks, measurement of malondialdehyde (MDA), reduced glutathione (GSH) concentrations, and cerebellar mRNA expression for AQP1 and AQP4 genes were performed. Immunohistochemical evaluation of AQP1, AQP4, and glial fibrillary acidic protein (GFAP) for cerebellar sections was performed for all groups. Diabetes caused degenerative changes in Purkinje cells with a significant increase in the cerebellar level of MDA and AQP1 immunoreactivity and a significant decrease in GSH level and AQP4 expression levels. However, the alteration in the AQP1 mRNA level was not statistically significant. GFAP immunoreactivity was increased in 8 W diabetic rats following its decrease in 1 W diabetic rats. Diabetes caused some alteration in the AQPs 1 and 4 expression in the cerebellum of diabetic rats which may contribute to diabetes-induced cerebellar complications.

Evaluation of the modulation of nitric oxide synthase expression in the cerebellum of diabetic albino rats and the possible protective effect of ferulic acid.

INTRODUCTION: Diabetes mellitus is a multisystem disease. Oxidative stress and nitric oxide isoforms are involved in diabetic pathogenesis. Ferulic acid is a natural substance that is distributed broadly in plants with strong potent properties. THE AIM OF THE RESEARCH: This research was designed to study the possible protective role of ferulic acid on oxidative stress and different Nitric oxide synthase isoforms (NOS) in the cerebellum of streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Twenty-four albino male rats were randomly divided into equal four groups: control group, group 2 received ferulic acid orally (10 mg/kg), group 3 diabetic group, group 4 diabetic rats received ferulic acid. After 8 weeks, the left cerebellar hemisphere was taken for tissue homogenate for oxidative markers and real-time PCR for NOS isoforms. Paraffin sections of the right cerebellar hemisphere were stained with cresyl violet, Luxol fast blue and immnunohistochemically stained for neuronal NOS, inducible NOS and endothelial NOS. RESULTS: Degenerative changes were seen in the cerebella of the diabetic rats with significant elevation of Malondialdehyde, Nitric Oxide, and decrease of Superoxide dismutase levels. nNOS expression decreased and iNOS expression increased significantly. The ferulic acid-treated group showed a reduction of the degenerative changes in the cerebellum with significant improvement in oxidative stress marker, an increase of nNOS expression, and a decrease of iNOS expression. CONCLUSIONS: Ferulic acid improves cerebellar functional and histopathological changes induced by diabetes which can be attributed mainly to its anti-oxidative effect and its ability to modulate NOS isoforms.

The neuroprotective effect of simvastatin on the cerebellum of experimentally-induced diabetic rats through klotho upregulation: An immunohistochemical study.

BACKGROUND: Diabetes mellitus is a multifactorial metabolic disorder that is complicated by multi-organ dysfunction including CNS. Klotho is an anti-aging protein expressed in Purkinje cells of the cerebellum. Klotho protects against the development of several neurodegenerative diseases. Simvastatin is a lipophilic statin that can enhance klotho expression. AIM OF THE STUDY: This study was designed to investigate cerebellar structural changes in diabetes, klotho expression in the cerebellum of diabetic rats and the neuroprotective effect of simvastatin. MATERIALS & METHODS: 24 adult albino rats were divided into 4 groups; control, simvastatin, diabetic (induced by single intraperitoneal injection of STZ 45 mg/kg) and diabetic treated by simvastatin (10 mg/kg once daily) after confirmation of diabetes. Rotarod test was performed for evaluation of motor coordination. Blood glucose and insulin levels were estimated for confirmation of diabetes. Reduced glutathione (GSH) and malonaldehyde (MDA) in cerebellar tissues were evaluated. The cerebellar samples were prepared for histological and immunohistochemical staining. RESULTS: The latency time on the rotarod was reduced in diabetic rats. Cerebellar structure was disturbed in diabetic group. Oxidative stress was evidenced by increased MDA and reduced GSH. Klotho expression was downregulated and caspase-3 was increased in diabetes. Simvastatin increased the latency time. Simvastatin diminished the changes in oxidative stress markers and succeeded to ameliorate the diabetic induced cerebellar changes. Simvastatin enhanced Klotho and diminished Caspase-3 expression. CONCLUSION: Simvastatin can ameliorate diabetic induced cerebellar changes through minimizing oxidative stress, enhancement of Klotho expression and reduction of apoptosis.