Bina Kumari Mehta’s research while affiliated with Birla Institute of Technology, Mesra and other places

Background: Minocycline a tetracycline antibiotic is known for anti-inflammatory and neuroprotective actions. Here we determine the therapeutic potential of minocycline against type 2 diabetes associated cognitive decline in rats. Methods: High fat diet (HFD) and low dose streptozotocin (STZ; 25 mg/kg) were used to induce diabetes in Sprague-Dawley rats. Fasting blood glucose and haemoglobin (Hb) A1c were measured in these animals. Cognitive parameters were measured using passive avoidance and elevated plus maze test. Hippocampal Acetylcholine esterase (AchE), reduced glutathione (GSH), cytokines, chemokine levels were measured and histopathological evaluations were conducted. The diabetic animals were then given minocycline (50 mg/kg; 15 days) and the above parameters were reassessed. MTT and Lactate dehydrogenase (LDH) assays were conducted on neuronal cells in the presence of glucose with or without minocycline treatment. Results: We induced diabetes using HFD and STZ in these animals. Animals showed high fasting blood glucose levels (>245 mg/dl) and HbA1c compared to control animals. Diabetes significantly lowered step down latency and increased transfer latency. Diabetic animals showed significantly higher AchE, Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and Monocyte chemoattractant protein (MCP)-1 and lower GSH levels and reduced both CA1 and CA3 neuronal density compared to controls. Minocycline treatment partially reversed the above neurobehavioral and biochemical changes and improved hippocampal neuronal density in diabetic animals. Cell line studies showed glucosemediated neuronal death, which was considerably reversed upon minocycline treatment. Conclusions: Minocycline, primarily by its anti-inflammatory and antioxidant actions prevented hippocampal neuronal loss thus partially reversing the diabetes-associated cognitive decline in rats.

Objectives: Type 2 diabetes (T2D)-associated cognitive impairment is highly prevalent especially among the geriatric population. Here, we investigate the role of exercise in T2D-associated cognitive decline in rats. Methods: T2D was induced using high-fat diet (15 days) followed by low-dose STZ (25mg/kg). The T2D animals were subjected to aerobic exercise on running wheel for 6 weeks. Effect of aerobic exercise on cognitive performance of T2D animals was measured using step-down and transfer latency tests. This was followed by the measurement of reduced glutathione levels in hippocampal homogenates. We also measured hippocampal AchE activity and levels of neuroinflammatory markers such as IL-1 β, TNF-α and MCP-1. Morphology and density of hippocampal neurons were also determined by histopathological studies. Results: Exercise led to the following changes in T2D animals. It led to decrease in fasting blood glucose level (<250 mg/kg) and HbA1c (8.5 ± 0.23) compared to diabetic (11.73 ± 0.14) animals and improved insulin resistance. There was an increase in step-down latency (p < 0.001) and a decrease in transfer latency (p < 0.01) suggesting improved cognitive function. A significant increase in GSH levels (1.828 ± 0.024) compared to diabetic group (1.52 ± 0.03; p < 0.001) and decrease in AchE activity (1.4 ± 0.05) compared to diabetic group (1.65 ± 0.03; p < 0.05) were also observed. It reduced the levels of neuroinflammatory markers such as IL-1β, TNF-α and MCP-1 (p < 0.01). Hippocampal sections showed higher CA1 and CA3 neuronal density (p < 0.001) than T2D group. Conclusion: We may conclude that aerobic exercise could partially reverse diabetes-associated cognitive decline by reducing oxidative stress and inflammatory milieu in T2D animal brain.

OBJECTIVE: The objective of the study was to characterize the mechanism associated with metabolic syndrome (MetS)-associated cognitive decline and determine the effect of minocycline on the above condition in mice. MATERIALs AND METHODS: We developed a HFHC diet-induced MetS model in mice. Diagnostic characteristics of MetS including waist circumference, lipid levels, blood pressure, and fasting blood glucose were measured in these Swiss albino mice. Cognitive parameters were measured using passive avoidance and elevated plus maze test. Hippocampal acetylcholine esterase (AchE), reduced glutathione (GSH), and cytokine levels were measured and histopathological evaluation conducted. The MetS animals were administered minocycline (50 mg/kg; 10 days) and the above parameters were measured. RESULTS: We successfully induced MetS using HFHC diet in mice. Animals showed significantly higher fasting blood glucose levels (P < 0.001), systolic blood pressure (P < 0.01), waist circumference (P < 0.001), low-density lipoprotein (P < 0.001), and triglyceride (P < 0.01) and reduced high density lipoprotein levels (P < 0.05) compared to control animals. Both scopolamine and MetS significantly lowered (P < 0.01) step-down latency and increased transfer latency (P < 0.001). MetS animals showed significantly higher AchE (P < 0.001) and tumor necrosis factor-α (P < 0.001) and Interleukin-1 β (P < 0.01) and lower GSH (P < 0.001) levels and reduced both CA1 (P < 0.001) and CA3 (P < 0.01) neuronal density compared to controls. Minocycline treatment partially reversed the above neurobehavioral and biochemical changes and improved hippocampal neuronal density in MetS animals. CONCLUSION: MetS led to hippocampal oxidative stress and neuroinflammatory changes with a corresponding loss of hippocampal neuronal density and cognitive decline. Anti-inflammatory and antioxidant property of minocycline may be responsible for its neuroprotective actions in these animals.

OBJECTIVE: The objective of the study was to characterize the mechanism associated with metabolic syndrome (MetS)-associated cognitive decline and determine the effect of minocycline on the above condition in mice. MATERIALs AND METHODS: We developed a HFHC diet-induced MetS model in mice. Diagnostic characteristics of MetS including waist circumference, lipid levels, blood pressure, and fasting blood glucose were measured in these Swiss albino mice. Cognitive parameters were measured using passive avoidance and elevated plus maze test. Hippocampal acetylcholine esterase (AchE), reduced glutathione (GSH), and cytokine levels were measured and histopathological evaluation conducted. The MetS animals were administered minocycline (50 mg/kg; 10 days) and the above parameters were measured. RESULTS: We successfully induced MetS using HFHC diet in mice. Animals showed significantly higher fasting blood glucose levels (P < 0.001), systolic blood pressure (P < 0.01), waist circumference (P < 0.001), low-density lipoprotein (P < 0.001), and triglyceride (P < 0.01) and reduced high density lipoprotein levels (P < 0.05) compared to control animals. Both scopolamine and MetS significantly lowered (P < 0.01) step-down latency and increased transfer latency (P < 0.001). MetS animals showed significantly higher AchE (P < 0.001) and tumor necrosis factor-α (P < 0.001) and Interleukin-1 β (P < 0.01) and lower GSH (P < 0.001) levels and reduced both CA1 (P < 0.001) and CA3 (P < 0.01) neuronal density compared to controls. Minocycline treatment partially reversed the above neurobehavioral and biochemical changes and improved hippocampal neuronal density in MetS animals. CONCLUSION: MetS led to hippocampal oxidative stress and neuroinflammatory changes with a corresponding loss of hippocampal neuronal density and cognitive decline. Anti-inflammatory and antioxidant property of minocycline may be responsible for its neuroprotective actions in these animals.

Diabetic neuropathy, a microvascular complication associated with diabetes, is one of the most common forms of neuropathy. Current rodent models of type 2 diabetes are mostly transgenic which fail to mimic human type 2 diabetes and its secondary complications, including peripheral neuropathy. Our aim is to develop a non-transgenic animal model of type 2 diabetic neuropathy which closely mimics the human disease. Methods: High-fat diet (HFD; normal pellet diet + lard) and a dual dose of streptozotocin (25mg/kg) were used to induce diabetes in Sprague-Dawley rats. Developments of neuropathy in these animals were measured using behavioral parameters like tail flick latency, pain threshold using randall selitto, and gait test. Nerve conduction velocity and histopathological evaluation of sciatic nerve were also carried out. Paclitaxel treated animals served as neuropathy controls. Results: The animals developed diabetes (blood glucose >250 mg/ dl; HbA1c 11.77 ±0.14%). All the classical symptoms of painful neuropathy, reduction in tail flick latency (p<0.05), reduced vocalization threshold in randall selitto (p<0.01), gait test showing a highly negative sciatic functional index (p<0.01) and reduced nerve conduction velocity (p<0.01) were evident in HFD-STZ animals. The above response was comparable to paclitaxel-treated neuropathy controls. Histopathological evaluation of sciatic nerves showed indications of sciatic nerve damage in HFD-STZ and paclitaxeltreated animals. The above neuropathic conditions were successfully reversed upon glibenclamide treatment (10 mg/kg) in HFD-STZ treated diabetic animals. Conclusion: Hence we successfully developed a cost-efficient non-transgenic model of diabetic neuropathy which closely mimics the characteristics of the human form of the disease. © 2017, Association of Pharmaceutical Teachers of India. All rights reserved.

Metabolic syndrome (MetS) is characterized by a cluster of disorders like obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia. All these disorders are responsible for the development of secondary morbid and co-morbid conditions. The current review focuses on the molecular pathogenesis of secondary late complications associated with metabolic syndrome including cognitive impairment, depressive disorder, neuropathy, arthritis and colorectal cancer. © 2015, International Journal of Pharmacy and Pharmaceutical Science.

Metabolic syndrome (MetS) is characterized by a cluster of disorders like obesity, insulin resistance, glucose intolerance, hypertension and dyslipidemia. All these disorders are responsible for the development of secondary morbid and co-morbid conditions. The current review focuses on the molecular pathogenesis of secondary late complications associated with metabolic syndrome including cognitive impairment, depressive disorder, neuropathy, arthritis and colorectal cancer.