Massachusetts General Hospital, Alzheimer's Disease Research Unit
Charlestown, MA, United States
Role of Neural Activity in Alzheimer's Disease
Principal Investigator
Mentors
Project Goals
Development of therapeutics for Alzheimer's disease (AD) has been hampered by a lack of clear understanding of the biology governing its progression. Until recently, the scientific community has been focusing predominantly on the nuanced molecular mechanisms leading to the onset of AD. These approaches have often disregarded perturbations of overall function of the neurons that are vulnerable to Alzheimer's disease. The research proposed by Dr. Ksenia V. Kastanenka and colleagues is designed to provide significant insight into this area of neural activity and contribute greatly to an unexplored aspect of the disease. The results of this study will build a stronger platform for successful therapeutic agent innovation.
Project Summary
The goal of this project is to explore the importance of neural activity perturbations on the development of AD using an animal model. Dr. Ksenia V. Kastanenka and colleagues are testing whether hyperactivity of neurons in the brain leads to AD pathology. To that end the researchers are expressing a light-sensitive protein in neurons that can be activated with brief flashes of light to induce hyperactivity in these neurons. Subsequently, they measure levels of calcium, which is an important signaling molecule in the brain, and visualizing amyloid plaques. These studies allow neurons to be studied in exquisite detail, using state-of-the-art technology. The team is also testing whether activation of neurons that normally play a role in silencing neural networks in the brain, by light, can restore the balance between excitation and inhibition.
This research will provide great insight into the area of neural hyperactivity that has been greatly unexplored and will build a stronger platform for innovation of successful therapeutic agents.
Publications
Kastanenka KV, Herlitze S, Boyden ES, Tsai L-H and Bacskai BJ. Optogenetics shed light on Alzheimer’s disease. EC Neurology ECO.01 (2017): 27-29.
Lee YF, Gerashchenko D, Timofeev I, Bacskai BJ, Kastanenka KV. Slow Wave Sleep Is a Promising Intervention Target for Alzheimer's Disease. Front Neurosci. 2020 Jun 30;14:705. doi: 10.3389/fnins.2020.00705. PMID: 32714142; PMCID: PMC7340158. 
Kastanenka KV, Calvo-Rodriguez M, Hou SS, Zhou H, Takeda S, Arbel-Ornath M, Lariviere A, Lee YF, Kim A, Hawkes JM, Logan R, Feng D, Chen X, Gomperts SN, Bacskai BJ. Frequency-dependent exacerbation of Alzheimer's disease neuropathophysiology. Sci Rep. 2019 Jun 20;9(1):8964. doi: 10.1038/s41598-019-44964-z. PubMed PMID: 31221985. 
Kastanenka KV, Hou SS, Shakerdge N, Logan R, Feng D, Wegmann S, Chopra V, Hawkes JM, Chen X, Bacskai BJ. Optogenetic Restoration of Disrupted Slow Oscillations Halts Amyloid Deposition and Restores Calcium Homeostasis in an Animal Model of Alzheimer's Disease. PLoS One. 2017 Jan 23;12(1):e0170275. doi: 10.1371/journal.pone.0170275. PMID: 28114405; PMCID: PMC5257003.
First published on: July 10, 2012
Last modified on: April 17, 2024