# The role of the Htr1B serotonin receptor in the neonate autoresuscitation reflex and embryonic serotonergic neurogenesis as a potential mechanism in Sudden Infant Death Syndrome

> **NIH NIH F31** · BAYLOR COLLEGE OF MEDICINE · 2024 · $48,974

## Abstract

Project Abstract/Summary
Sudden infant death syndrome (SIDS) is an idiopathic disease characterized by an unknown cause of death in
infants less than a year of age after a full autopsy, death scene investigation, and medical history review. SIDS
is a large subset of Sudden Unexpected Infant Death (SUID) which, according to the CDC, takes the lives of
3400 infants per year in the US alone and is one of the leading causes of deaths in neonates representing a
significant, unmet medical need. Although the underlying cause of SIDS remains unknown, carefully controlled
post-mortem studies have revealed subtle brainstem abnormalities to be present in many SIDS cases.
Researchers have found that, in subsets of SIDS cases, there are significant decreases in serotonin (5-
Hydroxytryptomine, 5-HT), tryptophan hydroxylase 2 (TPH2) levels (an enzyme necessary for 5-HT production),
and decreased binding affinity of some 5-hydroxytryptamine receptors. Notably, in some of the same SIDS
cases showing reduced serotonin levels, researchers also found a significant increase in the number of
serotonergic neurons (5-HT neurons), suggesting a negative feedback relationship between developmental
serotonin signaling and neurogenesis to regulate serotonergic neuron numbers. However, the functional
consequences of these serotonergic abnormalities associated with SIDS remains to be fully characterized. A
leading hypothesis in the field is that the failure in the autoresuscitation reflex is a common endpoint in many
SIDS cases. Autoresuscitation occurs when the infant stops breathing and falls into an apneic state due to
extreme hypoxic/hypercapnic conditions, typically thought to occur from lying in a face down position, as many
SIDS cases are found. As a last line of defense, the infant initiates deep gasping to reoxygenate the heart to
restart its cardiorespiratory system. Studies have shown that the loss, or acute perturbation, of 5-HT signaling
and/or neurons in neonate mice significantly impacts their ability to autoresuscitate or survive when they are
exposed to episodic anoxia, mimicking SIDS like, face down conditions. However, it is not clear which serotonin
receptors (5-HTr) play a role in the autoresuscitation reflex. I hypothesize that the loss of Htr1B function
negatively impacts the neonate autoresuscitation reflex and embryonic serotonergic neurogenesis, two
key processes thought to be functionally disrupted across a large subset of SIDS cases. To test my
hypothesis, we will utilize loss of function and conditional Htr1B knockout mouse lines in combination with our
closed loop automated robotic platform to characterize neonate cardio-respiratory function and autoresuscitation
reflex. Additionally, we will assay mutant mice using novel spatial transcriptomics (MERFISH) to examine activity
dependent genes as a proxy for respiratory network dynamics as well as genetic lineage tracing tools to
characterize developmental changes related to serotonergic neurogenesi...

## Key facts

- **NIH application ID:** 10901065
- **Project number:** 1F31HL168962-01A1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Dipak Patel
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $48,974
- **Award type:** 1
- **Project period:** 2024-09-16 → 2027-09-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10901065

## Citation

> US National Institutes of Health, RePORTER application 10901065, The role of the Htr1B serotonin receptor in the neonate autoresuscitation reflex and embryonic serotonergic neurogenesis as a potential mechanism in Sudden Infant Death Syndrome (1F31HL168962-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10901065. Licensed CC0.

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