# The Hippocampus and Brainstem in the Sudden Infant Death Syndrome

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2020 · $647,492

## Abstract

Project Summary
Despite the safe sleep campaign, SIDS remains the leading cause of postneonatal infant mortality in the
United States today, with an overall rate of 0.40/1000 live births. Our laboratory has provided compelling
evidence in 4 independent datasets of defects in the serotonergic (5-HT) network in the medulla (lower
brainstem) involved in protective responses to life-threatening challenges during sleep. These 5-HT defects
include significantly decreased levels (~26%) of 5-HT itself in SIDS cases compared to age-adjusted controls.
Over the last two decades, our group has provided substantial evidence, from studies using neurochemical
techniques in frozen tissue, that a subset of SIDS is characterized by serotonergic (5-HT) brainstem pathology
in regions involved in cardiorespiratory control and arousal. In 2015, we then reported a novel anatomic
finding, from light microscope studies, in the dentate gyrus (DG) of the hippocampus in a major subgroup of
SIDS cases (~40%) in a separate dataset. In this latter dataset, 5-HT brainstem neurochemical defects could
not be simultaneously sought because the hippocampal tissues were from formalin fixed brains in the archives
of the San Diego medical examiner's system. The dentate abnormality in SIDS is part of the spectrum of
granule cell dispersion (GCD), which is characterized prominently by bilamination of the granule cells (GCs),
so-called dentate bilamination (DB). DB and associated GC abnormalities in the SIDS cases had almost
exclusively been reported previously in patients with temporal lobe epilepsy (TLE), some of who died from
sudden unexplained death in epilepsy (SUDEP). We now ask: 1) Do cases of SIDS-DB also have 5-HT
brainstem pathology? 2) Does the combined entity of SIDS-DB and 5-HT pathology share molecular,
cellular, and genetic features with TLE and/or SUDEP? 3) Does SIDS-DB and 5-HT pathology represent
one of many entities on a spectrum of underlying, intrinsic temporal lobe vulnerabilities associated
with sudden death across life? In these scenarios, DB is postulated to be a developmental abnormality in
GC proliferation and/or migration, and a precursor lesion to Ammon's horn sclerosis in TLE. We will test the
overall hypothesis that the DG and medullary 5-HT network are both abnormal in the same SIDS cases,
and that SIDS cases with DB share molecular, cellular, and genetic features in common with TLE
and/or SUDEP. In four Specific Aims, we will test this hypothesis using a variety of state-of-the-art techniques,
including transcriptomics with laser capture microdissection in the granule cells of the hippocampus, and whole
exome sequencing in SIDS cases with DB. The study's potential impact is the discovery of a cause(s) of
large subgroup (40%) of SIDS that will lead to intervention strategies, as well as biomarkers to identify
living infants at risk. Understanding DB in SIDS also opens up avenues to elucidate the cellular and
molecular pathology of sudden unexplained death b...

## Key facts

- **NIH application ID:** 9933942
- **Project number:** 5R01HD090064-04
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** ROBIN Lynn HAYNES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $647,492
- **Award type:** 5
- **Project period:** 2017-09-08 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9933942

## Citation

> US National Institutes of Health, RePORTER application 9933942, The Hippocampus and Brainstem in the Sudden Infant Death Syndrome (5R01HD090064-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9933942. Licensed CC0.

---

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