Research Projects

Synaptic plasticity is the process of reshaping neuronal connections, which determines the functionality of neurons. In Alzheimer's disease patients, a decline in neurogenesis and bias in neural circuitry is observed, which is associated with oxidative stress (OS), a key pathological correlate in the progressive neurodegenerative process. However, little is known about how regulation of neural plasticity occurs during oxidative stress. Neuropeptide Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) plays important roles in neuronal survival, neuroprotection, inflammation, and immunomodulation. The proposed study aims to elucidate this missing link by exploring the influence of PACAP on neuronal plasticity and synaptic function under OS. Preliminary in vitro data suggests a possible association between PACAP and transcription factors like HIF, a protein stabilized under OS, in regulating dendritic architecture. The study also examines the influence of PACAP and its downstream targets on energy homeostasis and their influence on the regulation of dendritic architecture under OS. The proposed studies will fill a critical void in our understanding of how PACAP, along with other factors, regulates the transcriptional milieu to enhance dendritic architecture under OS. Aims 1 and 2 will elucidate the molecular mechanisms by which PACAP influences dendritic formation under oxidative stress, while Aim 2 will elucidate the mechanisms by which PACAP regulates mitochondrial functioning and neurite formation in cells exposed to oxidative stress.