Chronic administration of pioglitazone attenuates intracerebroventricular streptozotocin induced-memory impairment in rats

What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer’s disease, about the therapeutic strategies in Alzheimer’s research

“…Many of antioxidant drugs have also been tested in the STZ-icv animal sAD models, suitable for such task due to the chemical nature of STZ which leads to generation of intracellular free radicals, nitric oxide (NO) and hydrogen peroxide, and mitochondrial damage (Szkudelski 2001). In line with that, significant and progressive elevation of MDA and decrement of GSH level, respectively, as well as oxidative-nitrative stress have been found in the rat brain 1 to 8 weeks following the STZ-icv treatment (Sharma and Gupta 2001a;Sharma and Gupta 2002;Ishrat et al 2006;Pathan et al 2006;Shoham et al 2007;Kumar et al 2010;Saxena et al 2011), demonstrating resemblance to the oxidative stress condition in the human sAD patients post-mortem.…”

“…Memory impairment induced by 3 mg/kg STZ-icv dose in rats was successfully Water Maze test, which was accompanied by lowered oxidative stress (GSH and MDA levels) and improved cerebral glucose utilization (Pathan et al 2006;Kaur et al 2009). Additionally, pioglitazone treatment of STZ-icv mice significantly attenuated higher levels of brain AChE activity, and oxidative stress levels measured by TBARS and GSH.…”

“…Following the parenteral administration of high doses, STZ selectively destroys insulin producing/secreting β cells in the pancreas, causing DM type I in adult animals (Szkudelski 2001), while multiple parenteral treatment with low to moderate STZ doses causes insulin resistance by damaging insulin receptor (IR) signalling (Blondel and Portha 1989;Kadowaki et al 1984;Giorgino et al 1992). Intracerebroventricular administration of low, subdiabetogenic doses of STZ has been shown to induce cognitive (Mayer et al 1991;Lannert and Hoyer 1998) and brain cholinergic deficits (Hellweg et al 1992;Blockland andJolles 1993, 1994), oxidative stress (Sharma and Gupta, 2001a;Sharma and Gupta 2002;Ishrat et al 2006;Pathan et al 2006;Shoham et al, 2006;Kumar et al, 2010;Saxena et al, 2011) as well as decrement in brain glucose/energy metabolism (Nitsch and Hoyer 1991;Plaschke et al 1996;Lannert and Hoyer 1998;Hoyer and Lannert 2007), and insulin resistant brain state (Salkovic-Petrisic et al 2006;Gruenblatt et al 2007;Steen 2006;Lester-Coll et al 2006;Agrawal et al 2010). These STZ-icv induced effects have been extensively reviewed elsewhere Salkovic-Petrisic et al 2012), and will not be elaborated here.…”

The Application of Pectin-Insulin Patch on Streptozotocin-Induced Diabetic Rats: Implications in the Hippocampal Function

“…The risk of developing learning and memory deficits is highly dependent of the chronicity as well as the quality control of hyperglycaemia [2]. Adequate glycaemic control has been reported to ameliorate the cognitive disturbances in diabetes [23]. Herein, we are reporting the effects of transdermal application of a pectin insulin patch on learning and memory, hippocampal insulin receptor expression and hippocampal TNF α and CRP concentration in streptozotocin-induced diabetic rats.…”

“…Streptozotocin has been shown to selectively destroy the pancreatic beta-cells mainly via the production of free radicals [23]. As a result, there is a deficit in insulin production which leads to hyperglycaemia [24].…”