ROLE OF BDNF IN ENRICHED ENVIRONMENT MEDIATED AMELIORATION OF HYPOBARIC HYPOXIA INDUCED MEMORY IMPAIRMENT

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1 ROLE OF BDNF IN ENRICHED ENVIRONMENT MEDIATED AMELIORATION OF HYPOBARIC HYPOXIA INDUCED MEMORY IMPAIRMENT THESIS SUBMITTED TO BHARATHIAR UNIVERSITY, COIMBATORE, INDIA FOR THE DEGREE OF DOCTOR OF PHILOSOPHY IN ENVIRONMENTAL SCIENCES BY VISHAL JAIN UNDER THE SUPERVISION OF DR. G. ILAVAZHAGAN DEPARTMENT OF NEUROBIOLOGY DEFENCE INSTITUTE OF PHYSIOLOGY & ALLIED SCIENCES LUCKNOW ROAD, TIMARPUR, DELHI , INDIA SEPTEMBER, 2012

2 CERTIFICATE This is to certify that the thesis entitled Role of BDNF in Enriched Environment mediated amelioration of Hypobaric Hypoxia induced memory impairment submitted to the Bharathiar University, in partial fulfillment of the requirements for the award of the degree of Doctor of Philosophy in Environmental Sciences is a record of original research work done by Mr. Vishal Jain during the period of his research in the Department of Neurobiology at Defence Institute of Physiology and Allied Sciences, under my direct supervision and guidance and the thesis has not formed the basis for the award of any Degree/Diploma/Associateship/Fellowship or other similar title of any candidate of any university. Place: Delhi Date: (DR. G. ILAVAZHAGAN) COUNTERSIGNED

3 DECLARATION I, Vishal Jain hereby declare that the thesis entitled Role of BDNF in Enriched Environment mediated amelioration of Hypobaric Hypoxia induced memory impairment submitted to the Bharathiar University, in partial fulfillment of the requirements for the award of the degree of Doctor of Philosophy in Environmental Sciences is a record of original and independent research work done by me during under the supervision and guidance of Dr. G. Ilavazhagan, Scientist H, and it has not formed the basis for the award of any Degree/Diploma/Associateship/Fellowship or other similar title to any candidate of any university. Place: Delhi Date: (VISHAL JAIN)

4 ACKNOWLEDGEMENT This thesis is the end of my journey in obtaining my Ph.D. I have not traveled in a vacuum in this journey. This thesis has been kept on track and been seen through to completion with the support and encouragement of numerous people including my well wishers, my friends, colleagues and various institutions. This thesis would not have been possible without the guidance and the help of several individuals who in one way or another contributed and extended their valuable assistance in the preparation and completion of this study. First and foremost, I convey my gratitude to my Ph.D. supervisor Dr. G. Ilavazhagan who has supported me throughout my thesis with his patience and knowledge whilst allowing me the room to work in my own way. I attribute the level of my doctorate degree to his encouragement and effort and without him this thesis, too, would not have been completed or written. One simply could not wish for a better or friendlier supervisor. Under his guidance, I successfully overcame many difficulties and learned a lot. Despite his busy schedule he used to review my thesis progress, gave his valuable suggestions and made corrections. He has taught me both consciously and unconsciously how good research is done. I appreciate all his contributions of time, ideas, and funding to make my Ph.D. experience productive and stimulating. The joy and enthusiasm he has for the research was contagious and motivational for me, even during tough times in the Ph.D. pursuit. His unflinching courage and conviction will always inspire me and I hope to continue work with his supervision and noble thoughts in my further career. I am especially thankful to Dr. Shashi Bala Singh, Director, DIPAS for her expert and active involvement in my research. She took personal pain in facilitating my research that made my task much easier. She always encouraged me to learn new things and motivated me to update myself in my research area. I will always remain grateful for her support, without which it would not have been possible to achieve this goal.

5 I take this opportunity to sincerely acknowledge the Defence Institute of Physiology and Allied Sciences, Defence Research and Development Organization, Ministry of Defence, India for providing financial assistance in the form of Research Fellowship which buttressed me to perform my work comfortably. I am immensely thankful to my mentor Dr. Dipti N. Prasad who was a source of inspiration for me. Her valuable suggestions and personal guidance during my experiments are memories of a life time. I am grateful to her for the immense moral support and affection bestowed by her without which this target could never be accomplished. Her efforts in developing a healthy scientific temperament in me and other lab mates was a lesson to be remembered for times to come. Her constant perusal of my research work and personal advices at difficult times kept my spirits high. I convey my gratitude to Lt. Col. Devnandini Sharma, who provided immense moral support, inculcated scientific temperament and discipline during experimentation in the lab. She took personal pain and supported me during tough time in my family. I can never forget her kindness and helping attitude towards me. I extend my thanks to Mrs. Ruma Dutta, Dr. Nilofer Khan, Dr. Ekta Kohli and Dr. Jyotsna Prasad for providing me the required facilities and persistent support during my experiments. Their readiness to help, even out of the way, to facilitate scientific work is a lesson to be memorized. I place on records my sincere thankfulness to Dr. Sunil Kumar Hota and Dr. Kalpana Barhwal Hota, who constantly monitored the progress of my work. They readily extended their helping hand at times of need and gave valuable suggestions during the course of my study. Their constant encouragement, affection and immense faith are unforgettable. My sincere thanks to Dr. Zahid Khan for helping me prepare some of my manuscripts and response to reviewers and Dr. Rajkumar Tulswani for his immense support in providing me suggestions and all necessary help whenever I needed them. I also thank Dr. Shubha Shukla and Dr. Koushik Ray for helping me in mastering some of the techniques implemented during the present study. Their efforts and guidance was of much value during execution of my experimental plans. I also convey

6 my gratitude t0 Mr. Bhagwat Singh and Dr. Tripude who provided the animals used during the present study. The contributions of my colleagues during my experiments are praise worthy. I am thankful to Dr. Bharat Singh, Mr. Iswar Baitharu & Mr. Narendra Sharma for their constant support and help in conducting the experiments during my Ph.D tenure. The personal bondage shared with them provided strength to overcome several hurdles during the course of my studies. I extend my heartfelt thanks to Mr. Satyanarayan Deep, Mr. Gaurav, Ms. Megha and Ms. Neetu who consistently supported me and boosted my morale in hard times. I am also thankful to my trainees i.e. Ms. Manju Bala Samar, Mr. Aditya Chaudhary, Ms. Nivedita, Ms. Shrishti and Ms. Apoorva for their constant support at personal and professional level during my Ph.D. tenure. These fellows not only supported me during my experiments but also encouraged me to tackle many problems. Without friends like them, this milestone would have been difficult to be reached. My heartfelt thanks to Dr. Panchanan, Dr. S. Muthuraju, Mr. Amitabh, Mr. Alpesh, Ms. Khushbu, Ms. Heena, Ms. Preeti and Ms. Reena for the friendly and cordial environment they provided in the lab that helped me in focusing on my goal. I would like to specially convey my thanks to my colleague, my best friend Ms. Chhavi Goel for her kind support throughout my doctorate studies. She always stood with me in every situation. Her support and motivation is like a boon for me which helped me a lot in achieving my goals. The blessings of my parents, love of my brother and sisters were my strength that cannot be captured in words. I am also very delighted by affection of Mrs. Banu which gave me strength and motivation during discussion with my supervisor. At this juncture of my career, I convey my gratefulness to all those who have been instrumental in fulfilling my dream and solemnly vow to continue my pursuit of remedies for human suffering. (VISHAL JAIN)