# Wyoming Sensory Biology COBRE

> **NIH NIH P20** · UNIVERSITY OF WYOMING · 2021 · $287,393

## Abstract

Abstract
Women are much more likely than men to develop Alzheimer’s disease (AD) and related dementias, which are
associated with progressive disruption of circadian rhythms. Additionally, women are more likely than men to
develop circadian disorders, such as sleep disorders, and one particular feature of circadian dysfunction in
patients with AD and related dementias is “sundowning syndrome”, a poorly understood clinical phenomenon
characterized by agitation, aggression, and delirium during the early evening hours. Sundowing symptoms have
a major impact on the quality of life for both the patient and their caregivers, who are also more likely to be
women, and often lead to the decision to seek institutionalization. The neurobiology of sundowning remains
unknown, however the temporal periodicity of sundowning symptoms suggests a possible disturbance in the
master circadian clock, the suprachiasmatic nucleus (SCN) of the hypothalamus, or in the pathways by which
the SCN modulates particular rhythms. Rhythms of sleep-wake and locomotor activity (LMA) are regulated by
the SCN via a pathway through its major postsynaptic target, the subparaventricular zone (SPZ), to the
dorsomedial hypothalamus (DMH). Additionally, we recently demonstrated that the propensity for behavioral
aggression also follows a daily rhythm that is regulated by the SCN, via an additional pathway through the SPZ,
to the ventromedial hypothalamus (VMH). Importantly, disrupting this SCNSPZVMH pathway led to
increased aggression during the early resting phase (the light period for nocturnal mice), which is temporally
analogous to when AD and dementia patients who experience sundowning display increased agitation and
aggression. This suggests that the function of certain structures within this circuit may be compromised in AD
and dementia. Interesting, women have also been shown to have a particular profile of inflammatory markers in
AD, however these differences have never been examined directly in areas associated with circadian regulation.
We have begun examining circadian rhythms in the TAPP mouse model, which develops amyloid-beta (a-beta)
plaques and tau neurofibrillary tangles (both hallmarks of AD neuropathology), and our preliminary results
suggest that these mice exhibit increased early resting period aggression and disrupted LMA at very early ages
of AD pathology. In this proposal, we will examine whether sex-differences in specific inflammatory markers are
associated with sex differences in increased aggression during the early resting phase and disrupted LMA
rhythms in female and male TAPP mice, and in their female and male wild-type controls. We will focus our
analysis in a circuit-based and region-specific manner, by specifically examining lysates from dissected
hypothalamic tissue containing the SCN and SPZ, and dissected midbrain tissue containing areas which we
know project to the circadian system and which display heavy phosphorylated tau pathology at later ages.

## Key facts

- **NIH application ID:** 10395258
- **Project number:** 3P20GM121310-05S2
- **Recipient organization:** UNIVERSITY OF WYOMING
- **Principal Investigator:** Qian-Quan Sun
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $287,393
- **Award type:** 3
- **Project period:** 2017-09-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10395258

## Citation

> US National Institutes of Health, RePORTER application 10395258, Wyoming Sensory Biology COBRE (3P20GM121310-05S2). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10395258. Licensed CC0.

---

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