Coenzyme Q10 modulates cognitive impairment against intracerebroventricular injection of streptozotocin 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.…”

“…Additionally, a synthetic variant of CoQ 10 , idebenone, has been tested in clinical trials in which inconsistent results were obtained; better cognitive score in with 90 -120 mg doses only (Gutzmann et al 1998;Weyer et al 1997) and no effect with even higher doses in another trial . Contrary to that, neuroprotective effect of CoQ 10 was clearly demonstrated both at the cognitive and neurochemical level in the STZ-icv rat sAD model (Ishrat et al 2006). Supplementation with CoQ 10 (10 mg/kg b.w.…”

“…Supporting the hypothesis that the pathophysiology in the STZ-icv animal models shares huge similarities with the one in AD patients, cholinergic deficits have also been consistently found in various STZ-icv animal AD models (from newborn and adult rats to adult mice treated with STZ-icv), by demonstrating as a decrease in ChAT and an increase in AChE activity in the hippocampus, respectively (Hellweg et al 1992;Blokland and Jolles 1993;Blokland and Jolles 1994;Prickaerts et al 1999;Terwel et al 1995;Sonkusare et al 2005;Ishrat et al 2006;(Lester-Coll et al 2006; de la Monte et al 2006;Kumar et al 2010;Tota et al 2011). Importantly, AChE inhibitors tested so far, have been consistently successful in improving/preventing memory deficits in STZ-icv sAD models.…”

“…A decrease in hippocampal ChAT activity was completely prevented by a 2-week oral treatment of acetyl-L-carnitine which acts by enhancing the utilization of alternative energy sources Terwel et al 1995). Changes in both ChAT and AChE in the hippocampus were prevented by chronic intraperitoneal treatment with the antioxidant coenzyme Q10 (Ishrat et al 2006). Pretreatment with a hepatoprotectant silibinin (100 and 200 mg/kg, po) attenuated STZ-icv (1 mg/kg) induced memory impairment by reducing oxidative and nitrosative stress and synaptosomal calcium ion level, restored increased activity and mRNA expression of AChE and also significantly increased STZ-icv induced decrement in α-7-nAChR mRNA expression in addition to dose-dependent restoration of ATP levels (Tota et al 2011).…”

“…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.…”