# Role of extracellular vesicles in methamphetamine mediated neurotoxicity

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $318,730

## Abstract

Abstract:
Methamphetamine (Meth) and related amphetamine compounds, which are potent psychostimulants, are
among the most commonly used illicit drugs. With > 35 million users worldwide, Meth abuse poses a significant
health and economic threat globally. Acute and chronic doses of Meth have been shown to produce long-term
damage in many brain regions. However, the mechanisms underlying Meth neurotoxicity are still not known.
The current proposal focuses on one important and emerging player called
extracellular vesicles (EVs) and
their role in chronic Meth abuse. Extracellular vesicles (EVs) have been garnering increasing interest for their
role in several neurological disorders and understanding their role in the brain during drug abuse is just
beginning to emerge.
EVs can release their cargo into target cells and trigger downstream signaling pathways
.
Our own recent study has revealed that EV associated microRNA (miRNA) cargo can be responsible for
neuronal injury. However, EV miRNA cargo and their involvement in Meth associated neurotoxicity is not well
understood thus warranting further studies in this direction. We are particularly interested in understanding the
effect of such EV-carried miRNAs on neurons.
The overarching goal of this proposal is to examine the role of
EVs in the damaging effects of Meth on the central nervous system, specifically in a setting of chronic Meth
exposure. During course of this study, we will investigate several key questions in the field including molecular
and functional changes in neurons that are specifically driven by EVs during Meth abuse. These studies will be
conducted in three specific aims; (1) In Specific aim 1 we will utilize a robust strategy to isolate EVs from
archived monkey brain brains and from primary glial cells infected exposed to Meth, characterize them, and
determine Meth induced alterations in EV associated miRNA cargo. (2) Specific aim 2 is specifically designed
to study synaptodendritic injury and causative mechanism resulting from treatment with EVs isolated from
brains and primary glial cells from Meth treated groups and finally in (3) Specific aim 3, we will use a chronic
self-administration rat model to study the effects of brain EVs on neuronal damage and determine the
importance of sex as a variable. The experiments proposed in this study will unravel crucial signaling events
that mediate such neurotoxicity therefore providing a strong foundation to build further therapeutic studies for
the eventual prevention of long-term neuronal damage in Meth abuse that considers the role of sex.

## Key facts

- **NIH application ID:** 9963168
- **Project number:** 5R01DA042379-05
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Sowmya Yelamanchili
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $318,730
- **Award type:** 5
- **Project period:** 2016-09-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963168

## Citation

> US National Institutes of Health, RePORTER application 9963168, Role of extracellular vesicles in methamphetamine mediated neurotoxicity (5R01DA042379-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9963168. Licensed CC0.

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