# Preoptic/Hypothalamic Mechanisms of Sleep-Wake Regulation

> **NIH VA I01** · VA GREATER LOS ANGELES HEALTHCARE SYSTEM · 2026 · —

## Abstract

An estimated 54.1 million Americans, including 18.2 million Veterans (49% of the Veteran population),
are elderly and at higher risk for developing chronic sleep disturbance. Chronic insufficient or disrupted sleep
is associated with a spectrum of adverse health conditions, including anxiety, depressive disorders, obesity,
cardiovascular disease, cognitive decline, and Alzheimer's disease. Chronic neuroinflammation shares similar
health risks and a bidirectional relationship with sleep disruption.
 Recently, we found that chronic local inflammation in the preoptic-basal forebrain (POA-BF) of young
mice induces sleep disturbance resembling those in aging. Our preliminary data further suggests: a) that
lipopolysaccharide (LPS) given peripherally also triggers similar but late-onset sleep disruption after 8 weeks;
and b) that preoptic-hypothalamic (POA) tissues from LPS-treated and aged mice had higher levels of
microglia activation, a marker of neuroinflammation, lower levels of ATP-binding cassette transporter A1
(ABCA1) and higher intracellular cholesterol accumulation; lower levels of arginyltransferase1 (ATE1) and F-
actin; and an increased levels of caspase-3.
 We propose a series of innovative preclinical studies to investigate: a) can significant peripheral
inflammation induce lasting neuroinflammation in pivotal sleep-regulating systems, resulting in sleep
impairments similar to aging? b) does the decreased expression of ABCA1 and ATE1 during aging or chronic
neuroinflammation disrupt cholesterol balance, causing intracellular cholesterol accumulation and
cytoskeletal defects? do these changes cause dysfunction of critical sleep-regulatory systems leading to sleep
disturbances? and c) how effective are anti-inflammatory and cholesterol efflux-enhancing drugs in mitigating
sleep disturbances in aging or conditions characterized by chronic neuroinflammation?
Specific Aim 1: will determine if peripheral inflammation triggers lasting sleep-wake disruptions resembl

## Key facts

- **NIH application ID:** 11264635
- **Project number:** 5I01BX005167-06
- **Recipient organization:** VA GREATER LOS ANGELES HEALTHCARE SYSTEM
- **Principal Investigator:** Noor  Alam
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2026
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2021-01-01T00:00:00 → 2028-12-31T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11264635

## Citation

> US National Institutes of Health, RePORTER application 11264635, Preoptic/Hypothalamic Mechanisms of Sleep-Wake Regulation (5I01BX005167-06). Retrieved via AI Analytics 2026-06-24 from https://api.ai-analytics.org/grant/nih/11264635. Licensed CC0.

---

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