PhD Transfer Exam – Sara Pintwala (Peever lab)

PhD Transfer Exam

Thursday May 11^th, 10:10 am – Ramsay Wright Building, Rm. 432

Sara Pintwala (Peever lab)

“Central nervous system cell transplants: a new model for disordered sleep”

Abstract

Narcolepsy is an autoimmune disorder affecting three million people worldwide. This disorder is characterized by degeneration of 85-95% of neurons in the lateral hypothalamus producing orexin, a neurotransmitter essential for arousal stability. This results in undetectable levels of orexin in the central nervous system (CNS) and the onset of debilitating symptoms such as excessive daytime sleepiness and a sudden loss of postural muscle tone, termed cataplexy. Presently there is no cure for narcolepsy. By the nature of this disorder it could be reasoned that reinstating orexin neurotransmission will lead to a recovery of function and behavior. Cell transplant experiments to cure disease have before proven successful, but are dependent on the availability of neurons of identical phenotype to the cells lost. Thus, the goal of my project is to investigate the character of three novel hypothalamic cell lines and to determine the consequences of transplantation of these neurons into the CNS in a mouse model of narcolepsy. First, I will characterize three novel hypothalamic, and putatively orexinergic, cell lines. Second, I will determine survival of these cultured neurons in the CNS post-transplantation. Thirdly, I will demonstrate reversal of the behavioural abnormalities associated with narcolepsy. Lastly, I will demonstrate the recovery of orexin neurotransmission in the CNS with microdialysis. I hypothesize that the hypothalamic cell lines described here are of an orexinergic phenotype, will survive transplantation into the CNS and reverse narcoleptic symptomatology. If these novel hypothalamic cell lines possess characteristics and morphology similar to that of their in vivo counterparts, their transplant and survival in the CNS will represent a novel therapeutic target for narcolepsy and cure this disorder. This proposal has significant implications for clinical interventions for narcolepsy, but also provides significant insight into the field of cell transplantation.

Ramsay Wright is a wheelchair accessible building.