# 5/13 ALK and Midkine as Novel Neuroimmune Regulators of Alcohol Consumption

> **NIH NIH U01** · UNIVERSITY OF ILLINOIS AT CHICAGO · 2020 · $388,554

## Abstract

One of the goals of the Integrative Neuroscience Initiative on Alcoholism (INIA)-Neuroimmune
consortium is to understand brain immune signaling systems and their role in the causes and treatments of
alcohol dependence. As part of INIA, we have identified the receptor tyrosine kinase, anaplastic lymphoma
kinase (ALK) and its putative secreted ligand midkine (MDK), as novel signaling proteins that may be involved
in alcohol use disorders. ALK and MDK are known to signal through immune response pathways in the body,
but the roles of ALK and MDK in immune signaling specifically in the brain in response to ethanol have not
been examined. The objective of the first Specific Aim of this project is to identify ethanol-responsive MDK- and
ALK-dependent neuroimmune signaling pathways in the brain using MDK and ALK inhibitors. This will be done
by treating mice either with a single dose of ethanol or allowing mice to drink alcohol. Phosphorylation of
proteins involved in neuroimmune signaling pathways will be measured in the first experiment. In the second
experiment, expression of genes encoding cytokines and chemokines will be tested. In the third experiment,
activation of microglia, the resident immune cells in the brain, and astrocytes, which are activated by
inflammatory processes, will be examined.
 Small-molecule inhibitors targeting ALK are effective in reducing binge-like drinking in mice, suggesting
that ALK is a potential therapeutic target for the treatment of alcohol use disorders. The mechanism(s) through
which ALK acts to regulate excessive drinking are not well understood. Evidence from our INIA work suggests
that ALK might act in the central nucleus of the amygdala (CeA), a key brain region involved in ethanol
dependence, to regulate excessive ethanol consumption and GABA neurotransmission. The goal of the
second Specific Aim of this project is to test for effects of MDK and ALK manipulation in the CeA on these two
parameters. Three experiments will be performed. The first involves viral delivery of short hairpin RNAs
targeting ALK or MDK directly into the CeA. In the second and third experiments, we will infuse ALK and MDK
inhibitors, or recombinant MDK protein, into the CeA. Mice will be tested for binge-like ethanol consumption
and for GABA-mediated inhibitory currents by electrophysiology after infusion.
 Another goal of INIA-Neuroimmune is to use new technologies to study neural circuits involved in the
development of excessive alcohol drinking. To this end, the objective of the third Specific Aim is to develop and
produce cutting-edge viral vectors for INIA investigators for selective knockdown, knockout, or overexpression
of genes. These vectors will be provided to INIA investigators for delivery to specific brain regions involved in
alcohol dependence. This will allow for the identification of the neural pathways in which INIA candidate genes
function to control alcohol drinking. This proposal involves numerous interactions with INI...

## Key facts

- **NIH application ID:** 9853702
- **Project number:** 5U01AA020912-10
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT CHICAGO
- **Principal Investigator:** Amy Wolven Lasek
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $388,554
- **Award type:** 5
- **Project period:** 2011-09-05 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9853702

## Citation

> US National Institutes of Health, RePORTER application 9853702, 5/13 ALK and Midkine as Novel Neuroimmune Regulators of Alcohol Consumption (5U01AA020912-10). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9853702. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*