Histopathological and Behavioral changes in Cerebellum in Experimental models on Administration of kainic Acid followed by Nicotine

Abstract

Neurodegenerative diseases such as Alzheimer s, Parkinson s, Huntington s and newlineamyotrophic lateral sclerosis are multifactorial debilitating disorders of the nervous newlinesystem that affect approximately 30 million individuals worldwide. These diseases arise by abnormal protein dynamics with defective protein degradation and aggregation. newline newlineAlthough a lot of research has been carried out to understand the pathophysiology of newlinethese disorders, each of these disease has its own molecular mechanism and clinical manifestations. Despite the extensive efforts that have attempted to define the molecular mechanisms underlying neurodegeneration, many aspects of these pathologies remain elusive. In light of the recent achievements in the field of elucidating the pathophysiological aspects, the excitotoxicity is considered as an important mechanism involved in various neurodegenerative diseases of central nervous system (CNS). In the past decades, there has been great achievements in the elucidating excitatory signalling pathways in different neurodegenerative diseases of brain. In line with the above, recent studies on neurophysicochemical aspects suggest that cerebellum also could participate in excitotoxicity. In order to investigate the possible involvement of cerebellum in the excitotoxicity, an animal model that mimics the pathogenesis of excitotoxicity in neurodegenerative diseases should be considered. Thus, Kainic acid, an analogue of excitotoxic glutamate that induces neurodegeneration in rodents has been considered for the present research. Although many therapeutic approaches have been tested, no effective cure for these neurodegenerative diseases has been identified till date. Recent findings of nicotine effects on neuroprotection claimed it as a potential tool for the treatment of neurodegenerative disorders. In view of the above, my research addresses the question how nicotine protects the KA induced excitotoxicity and the underlying newlinemechanisms involved in neurodegeneration.We have utilized 24 adult male albino rats of wistar strain weighing 135-150 grams to study the possible therapeutic role of nicotine on the reversal of kainic acid induced excitotoxic cerebellar newlineneurodegeneration. The rats were divided in to four groups each consisting of 6 newlineanimals. The control group(Group-I) was given 0.9% saline as vehicle and the newlineexperimental groups (group-II with 1mg/kg Nicotine; group III- Kainic acid 1mg/kg; newlineIV- Kainic acid followed by Nicotine 1mg/kg bodyweight) were given intraperitoneal newlineinjections respectively for a period of 28 days. All the animals were sacrificed on the newlinelast day of experiment to study the histopathological and behavioral changes in newlinecerebellum. Kainic acid followed by Nicotine treated group animals showed less degeneration in the cerebellar cortex. Furthermore, minimal damage was observed inthe white matter of the cerebellum on histopathological examination, and there wassignificant improvement in motor co-ordination and behavioral activity in the samegroup animals. The present study reveals that long term administration of nicotinehas a protective role against excitotoxicity induced by kainic acid and its analogues incerebellum of experimental models and the mechanism of actions and cell mediatedprocess are yet to be evaluated by using different methods. newline newline