# The striatal cholinergic interneurons in Parkinson's disease and treatment

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $462,557

## Abstract

Project Summary/Abstract
Dopaminergic therapy in Parkinson’s disease (PD) is the most successful example of rationale treatment
approach addressing neurotransmitter deficit in neurodegenerative disorders. However, it is limited by
motor fluctuations including dyskinesia that develops over several years of treatment. It is not clear if
disease progression or treatment is the major factor in producing L-DOPA-induced dyskinesia (LID), but
clinical and experimental evidences point to contributions of age of onset, disease severity, and chronic
dopaminergic drug exposure. We have recently reported that elevated cholinergic signaling may be a
major contributor to LID. Repeated L-DOPA administration in parkinsonian mice produces LID, which is
associated with hyperexcitability of striatal cholinergic interneuron (ChI) evidenced by extracellular
signal-regulated kinase (ERK) activation and enhanced response of ChI to dopamine. Moreover, the
expression of LID was partially attenuated by preventing ERK activation or a muscarinic receptor
antagonist. Ablation of ChI dramatically reduces LID in a mouse model of PD created by 6-OHDA lesion.
To define the role of ChI further, we will utilize a novel method of selectively activating or suppressing
ChI by Designer Receptor Exclusively Activated by Designer Drug (DREADD) system using transgenic mice
expressing Cre in ChI and adenovirus-mediated delivery of floxed construct of DREADD to the striatal ChI.
We will determine the role of ChI in LID development and expression separately. The outcome of this
experiment would indicate fundamentally different approaches, either as a prophylaxis to
prevent LID development or for symptomatic control of LID expression once it has already
developed. We will then characterize cellular mechanisms of ChI hyperactivity associated with LID by
examining gene expression changes, morphological alterations and electrophysiological properties.
Multidisciplinary approaches will provide us necessary insights and tools to devise therapeutic
approaches to LID.

## Key facts

- **NIH application ID:** 9950866
- **Project number:** 5R01NS101982-04
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Un Jung Kang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $462,557
- **Award type:** 5
- **Project period:** 2017-05-01 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9950866

## Citation

> US National Institutes of Health, RePORTER application 9950866, The striatal cholinergic interneurons in Parkinson's disease and treatment (5R01NS101982-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9950866. Licensed CC0.

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