Normobaric hyperoxia preconditioning attenuates streptozotocin - induced impairments in spatial learning

Introduction: A large body of evidence points to oxidative stress as prime candidate mediating the behavioral impairments and memory deficits in Alzheimer's disease (AD). It has been demonstrated that hyperoxia preconditioning activates complex endogenous neuroprotective mechanisms including an increase in capacity of antioxidant defence mechanisms. The aim of this study was to investigate the beneficial effects of normobaric hyperoxia preconditioning in streptozotocin (STZ)induced memory impairment in rats. Materials and Methods: Male Wistar rats were first exposed to air with high oxygen concentration (>90%) or atmospheric air for 24 hours and then STZ (3 mg/kg) was bilaterally infused in lateral ventricles of the brain. Two weeks later Morris Water Maze (MWM) test was performed to assess spatial learning and memory consolidation. Results: STZ increased escape latency (P<0.05), distance and number of crossed quadrants (P<0.05) especially on 1st and 2nd days. However, hyperoxia preconditioning significantly attenuated STZ-induced learning and memory deficits during training sessions in the MWM (P<0.05). Preconditioning also increased time spent and swimming distance in the target quadrant in probe test (P<0.05). However, hyperoxia preconditioning had no effect on the swimming speed. Conclusion: Hyperoxia preconditioning significantly attenuated STZ-induced impairments in spatial learning and memory. These results suggest that hyperoxia may have a potential therapeutic effect at the early stage of AD and possibly the prevention of memory deficits. D ow nl oa de d fr om w w w .p hy ph a. ir at 1 7: 58 IR S T o n M on da y O ct ob er 5 th 2 01 5 hyperoxia preconditioning attenuates memory impairments by STZ Physiol Pharmacol 19 (2015) 130-138 | 131 prime candidate causing the behavioral impairments and memory deficits observed in AD (Launer et al., 1998, Cantuti-Castelvetri et al., 2000). Free radicals such as hydroxyl radicals and hydrogen peroxide can be formed in cells during aerobic metabolism of endogenous and exogenous substances. Cells have enzymatic and non-enzymatic scavenger systems to remove these free radicals. However, if free radical production and scavenger systems remain unbalanced, cells are exposed to oxidative stress damage, resulting in cell injury (Parinandi et al., 1990, Griesmacher et al., 1995). Thus, antioxidants have been considered as having putative positive benefits in altering, reversing or a potential treatment of Alzheimer’s dementia. It is well known that if the noxious stimulus below the threshold of damage to the tissue is applied, of damage.(sentence may need to be rephrased) This phenomenon which is called preconditioning has been demonstrated in a variety of organs such as heart, kidney, and brain. preconditioning involves complex endogenous protective mechanisms including an increase in capacity of antioxidant defense mechanisms (Cadet et al., 2009), inhibition of mitochondrial permeability, transition pore opening (Hausenloy et al., 2009), and inhibition of excitotoxicity/(cytotoxicity??) through down regulation of NMDA and AMPA receptors (Tanaka et al., 2002). Preconditioning has attracted the interest of clinical and basic neuroscientists and the studies over the past decade have resulted in various promising strategies for the treatment of patients with acute brain injury. Several strategies have been tested in randomized clinical trials (Dirnagl et al., 2009). although the causes of neurodegeneration are different both in acute (such as stroke) and chronic n forms (such as Alzheimer's disease (AD) and Parkinson's disease), but the mechanisms leading to neuronal death including mitochondrial dysfunction, apoptosis, and caspase activation are the same (Soane et al., 2007). Therefore, preconditioning strategies may prevent or attenuate the neuronal death in chronic neurodegenerative disorders too. In this study, we examined the effect of normobaric hyperoxia preconditioning on learning and memory deficits in streptozotocin (STZ)-induced AD in rats. Intracerebroventricular (i.c.v.) injection of STZ causes behavioral impairments including prolonged impairment in learning and memory which resemble AD (Blokland et al., 1993, Lannert et al., 1998). Moreover, i.c.v. injection of STZ, in a subdiabetogenic dose produces oxidative stress and several authors have attributed the cognitive impairment in STZinduced AD to STZ-induced oxidative stress (Sharma et al., 2001, Raza et al., 2012). Materials and methods