Understanding Meth’s Impact, One Cell at a Time

A team of researchers from the University at Albany and the University at Buffalo are using Raman spectroscopy to examine how Methamphetamine use impacts neural cells.

ALBANY, N.Y. (April 24, 2019) – While the opioid crisis in the United States draws most of the headlines, other dangerous drugs continue to hold communities in the grip of addiction, perhaps none as prominently as methamphetamine, or "meth" for short. Associated with the television show “Breaking Bad” and for its production in household labs, the drug remains highly lethal, and according to The New York Times, more of it is available in the United States than ever before.

From left, Research Associate Professor of Medicine Supriya Mahajan (University at Buffalo), Assistant Professor of Physics Alexander Khmaladze (University at Albany), and Assistant Professor of Physics Jonathan Petruccelli (University at Albany)

A team of SUNY researchers at the University at Albany and the University at Buffalo are hoping to use new technologies to understand just how meth reacts with the mitochondria in cells, and hopefully find better ways to treat the drug’s devastating impact.

The research team, consisting of UAlbany assistant professors of Physics Alexander Khmaladze and Jonathan Petruccelli and Research Associate Professor of Medicine Supriya Mahajan from the Jacobs School of Medicine and Biomedical Sciences, Department of Medicine at the University at Buffalo, have been awarded $1.1 million through the National Institutes of Health National Institute of Drug Abuse to examine meth addiction treatment on mitochondrial respiration.

Methamphetamine abuse causes neuronal apoptosis, or rapid cell death in humans. This can result in a spectrum of mild to moderate neurocognitive disorders that may progress to dementia. But while the damage caused by meth addiction may be readily apparent, Khmaladze and Petruccelli are hoping their technique for analyzing this interaction -- Raman spectroscopy -- will help doctors and scientists develop new therapies for addiction treatment and exposure response.

“We are employing Raman spectroscopic technique to detect meth-induced chemical changes within neurons, mitochondrial protein expression, and the distribution change in cytochrome C during apoptosis,” said Khmaladze. Neurocognitive disorders are a result of damage to the nerve terminals of dopamine-producing neuronal cells that trigger activation of apoptotic mechanisms, causing death of brain cells, including neurons, astroglia and microglia.

Chronic use of meth, an addictive psychostimulant, produces neurotoxicity by causing microglial activation and the secretion of pro-inflammatory cytokines, which leads to neural injury and cell demise. Mahajan said that their study is based on the hypothesis that “Meth treatment significantly impacts mitochondrial respiration and induces activation of the mitochondrial-dependent intrinsic apoptotic pathway, resulting in neuronal cell death.”

“Our project utilizes innovative optics-based methodologies, such as three dimensional quantitative phase imaging and Raman spectroscopy, to study Methamphetamine-induced cell apoptosis in primary neurons in real time,” said Petruccelli. “By monitoring cell apoptosis in human neurons non-invasively, in real time using quantitative phase imaging (QPI), we can observe the morphological changes in the affected cells.”

The researchers believe their approach offers some significant advantages over the current methods, including compatibility at low cost with existing bright-field microscopes, greater stability and robustness to vibration and improved spatial resolution. Further, by monitoring their Raman spectroscopic signatures during various stages of cell apoptosis, they will be able to detect chemical changes and protein content within neurons and other neuronal cells.

“Apoptosis is a rapid process,” continued Khmaladze. “It is, therefore, a challenge to study the dynamics of protein-protein and protein-membrane interactions in apoptotic cells in-vivo, determine structural changes in membrane-bound proteins, and capture conformational changes in response to apoptotic stimuli in real time, all of which are key to understanding the mechanisms of both apoptosis induction and execution.”

The relationship between apoptosis and the cell cycle, and the paradoxical effect of some inducers of cell death in cell proliferation has made it difficult to understand and identify apoptosis-specific regulatory mechanisms.

Khmaladze, Petruccelli and Mahajan hope to overcome these challenges by using advanced optics tools, such as QPI and Raman spectroscopy.

“With the tools at our disposal, we can achieve important advances in molecular identification of the cell death machinery,” said Petruccelli. “Our proposed multi-institutional, interdisciplinary project will employ a new imaging techniques to evaluate mitochondrial dynamics, which will advance both fundamental and applied aspects of biophysical research.”

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