# Investigating the role of astrocytes on neuronal activity and behavioral modulation

> **NIH NIH K01** · NEW YORK INST OF TECHNOLOGY · 2020 · $143,014

## Abstract

Project Summary/Abstract:
 This proposal describes a four-year training project, which will prepare the applicant to achieve the goal
of becoming an independent investigator in diabetes and neurobiology research. The research proposed here
aims to better understand insulin and IGF-1 signaling in the brain, which will have potential implications for
public health. The applicant also proposes a detailed training plan, which includes further training in specialized
techniques and attending scientific and career development seminars and courses. The applicant has
assembled an outstanding Boston-based mentoring team to support the research as well as career
development throughout the training period. The applicant will be co-mentored by Dr. C. Ronald Kahn, a
renowned expert in insulin signaling and diabetes research, at Joslin Diabetes Center, Harvard Medical
School, and Dr. Philip Haydon, a pioneer and expert in astrocyte biology and gliotransmission, at Tufts
University College of Medicine. In addition, the applicant will receive technical and intellectual support from
scientific advisors Drs. Emmanuel Pothos and Bradford Lowell.
 Insulin is known to act in the brain to suppress appetite and to improve cognition and depression
symptoms. Patients with diabetes have a greater risk to develop neurological disorders, including Alzheimer's
disease and major depression. Loss of insulin receptors in the brain leads to overfeeding, insulin resistance
and more depressive-like behaviors in mice. All of these indicate that insulin is a key regulator to maintain
normal neurophysiology. However, the mechanism by which insulin signaling in the brain controls
neurobehaviors is still not fully understood. My preliminary studies show that mice with astrocyte-specific
insulin receptor deletion exhibit increased depressive-like behavior, which indicates that insulin signaling
originated from astrocytes is important for regulation of neuronal activity and behaviors. The overall goal of
this project is to characterize the relative roles of insulin receptor (IR) and IGF-1 receptor (IGF1R) in astrocytes
for neural functions and behaviors. The central hypothesis is that IR, and possibly IGF1R, signaling is
important for normal metabolism and function of astrocytes, and that loss of these actions will lead to altered
neurotransmitter homeostasis, which secondarily modulates dopaminergic neuronal activity, thus altering
behaviors. Aim 1 will define the cell autonomous roles of IR and IGF1R in astrocytes on the regulation of
intracellular signaling, cellular metabolism, neurotransmitter release, which could contribute to neuronal
regulation. Aim 2 will examine the roles of IR and IGF1R in astrocytes on dopaminergic neural circuitry and
mood regulation in normal and diabetic conditions. These studies will expand our knowledge of IR and IGF1R
signaling in the brain under normal physiological condition and in the context of diabetes and insulin
resistance, and could provide new ...

## Key facts

- **NIH application ID:** 10099014
- **Project number:** 7K01DK120740-03
- **Recipient organization:** NEW YORK INST OF TECHNOLOGY
- **Principal Investigator:** Weikang Cai
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $143,014
- **Award type:** 7
- **Project period:** 2019-03-26 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10099014

## Citation

> US National Institutes of Health, RePORTER application 10099014, Investigating the role of astrocytes on neuronal activity and behavioral modulation (7K01DK120740-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10099014. Licensed CC0.

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