ISSN 2320-5407 International Journal of Advanced Research (2016), Volume 4, Issue 1, 959- 994 959 Journal homepage: http://www.journalijar.com INTERNATIONAL JOURNAL OF ADVANCED RESEARCH RESEARCH ARTICLE Differential responses of amygdala and hippocampus consequent to Aβ 40 and Aβ 42 induced toxicity in the rat brain: A comparative study. Neha Mishra, Rameshwar Singh, Deepak Sharma * School of Life Sciences, Jawaharlal Nehru University, New Delhi, India. Manuscript Info Abstract Manuscript History: Received: 14 November 2015 Final Accepted: 22 December 2015 Published Online: January 2016 Key words: Amygdala; Hippocampus; Oxidative stress; Amyloid beta- protein (1-40); Amyloid beta- protein (1-42); Cognition; Social behavior. *Corresponding Author Deepak Sharma. Amyloid beta (Aβ) peptides are the principal constituents of senile plaques of Alzheimer’s disease (AD) brain, and are thought to play an important role in the etiology and pathogenesis of AD. The present study assesses the responses of brain regions (hippocampus and amygdala) to amyloid toxicity in the light of behavioral and oxidative parameters. Aggregated Aβ 40 and Aβ- 42 were stereotaxically injected into the hippocampus or amygdala, and their effects on cognitive (Morris water maze test) and non-cognitive (fear, anxiety, general emotional state: open field and light and dark chamber tests) behaviors were studied. Since human-specific social behaviors (empathy, sympathy etc.) also exist in rodents, the effect on these behaviors was also determined by three-chamber social behavior test. The oxidative stress generated by amyloid-β peptides is thought to contribute to the disease- associated behavioral deficits. Therefore, the present study also investigated the oxidative stress produced in the rat brain following amyloid injections. The oxidative stress produced by Aβ peptides was higher in the hippocampus compared with that in the amygdala. Similarly greater behavioral anomalies were caused in animals with intrahippocampal administration than in those with intraamygdalar administration. Thus, hippocampus showed a higher vulnerability to amyloid toxicity than amygdala. Furthermore, the results demonstrated that the oxidative stress spread from the injected site to distant brain regions like cortex, midbrain, cerebellum, and medulla. The results also showed that compared with Aβ 40 , Aβ 42 generated higher levels of oxidative stress and produced more severe behavioral deficits. . Copy Right, IJAR, 2016,. All rights reserved. Introduction:- The deposition and accumulation of amyloid β-peptide (Aβ) in neuritic plaques and neurotoxicity of Aβ are considered central to the pathogenesis of Alzheimer’s disease (AD) (Hardy et al., 1991; Hardy et al., 1992; Masters et al., (1985); Wisniewski et al., 1994). Exogenously injected Aβ rodent model is a common model used in t he Alzheimer’s disease related research. The amyloid plaques are said to be the loci of oxidative stress as Aβ can produce reactive oxygen species (Behl et al., 1992; Behl et al., 1994; Pike et al., 1991). AD brain cells exhibit abnormally high amounts of oxidatively modified proteins (Hensley et al., 1995; Lyras et al., 1997; Smith et al., 1991), lipids (Hajimohammadreza et al., 1990; Hensley et al., 1995; Lovell et al., 1995; Lovell et al., 1997; Lyras et al., 1997; Marcus et al., 1998; McIntosh et al., 1997; Subbarao et al., 1990.), and DNA (Gabbita et al., 1998; Markesbery et al., 1999; Mecocci et al., 1994.). Aβ peptide-induced oxidative stress is also thought to contribute to cognitive deficits (Jhoo et al., 2004). Characteristic behavioral symptoms associated with AD are of great clinical interest and numerous researchers have administered different amyloid peptides into the brain to study various behavioral anomalies and biochemical effects, yielding many contradicting reports of amyloid toxicity (Borbély et al., 2014; Cioanca et al., 2014; Cleary et