Background:The possibility of exposure to a considerable amount of electromagnetic waves exists all around us. The hippocampus is involved in spatial memory and learning processes which could be compromised by exposure to cell phone emitted radiofrequency (RF)-electromagnetic field (EMF .( Objective: To explore the effect of exposure to EMF on hippocampal function and to throw more attention on the mechanisms of interaction in the form of hippocampal acetylcholine (ACh), glutamate, malondialdehyde (MDA) and hippocampal cellular responses mediated by autophagy (Atg7 gene expression) and mitochondrial repair mechanism (SIRT1( Subjects and Methods: This study was performed on 39 young apparently healthy male Wistar albino rats, initially weighing 70-90 grams. They were randomly divided into three equal groups: control group (group I), cell phone-EMF exposed group (group II), which was exposed to cell phone, 2 hours/day, 6 days/week for 12 weeks, and alpha lipoic acid-treated cell phone-exposed group (group III) which was exposed to EMF as group 2 and received i.p injection of alpha lipoic acid in a dose of 50 mg/kg for the last 3 weeks of cell phone exposure. Twelve weeks later, all rats were subjected to cognitive function test for learning and spatial memory using Morris water maze. Body weight changes and liver function tests (ALT and AST) were evaluated, then hippocampal levels of glutamate, ACh, MDA, gene expression of Atg7 and SIRT1 were measured.Results: Compared to the control rats, cell phone exposure in group II did not alter the cognitive function test and the hippocampal glutamate level, but it caused significant rise in hippocampal MDA and acetylcholine levels, though there was a higher non-significant increased expression of SIRT1 and Atg7. Lipoic acid treatment concomitant with EMF exposure induced increase in the time spent in target quadrant with shortened time to reach the platform on fifth day of training compared to the controls. Also, lipoic acidtreated cell phone exposed rats exhibited significantly enhanced hippocampal glutamate level accompanied by significantly reduced hippocampal MDA and acetylcholine levels compared to control rats and preserved higher but non-significant levels of SIRT1 and Atg7 expression. Conclusion:Increased hippocampal ACh and expression of SIRT1 and Atg7 could be the early protective response against the higher MDA with exposure, thereby preventing the negative impact of EMF exposure on learning and spatial memory. Lipoic acid treatment improved cognition by increasing glutamate necessary for long term potentiation and decreasing hippocampal MDA.