Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome

Abstract

Infants at risk of sudden infant death syndrome (SIDS) have been shown to have dysfunctional sleep and poor arousal thresholds. In animal studies, both these attributes have been linked to impaired signalling of the neuropeptide orexin. This study examined the immunoreactivity of orexin (OxA and OxB) in the tuberal hypothalamus (n = 27) and the pons (n = 15) of infants (1-10 months) who died from SIDS compared to age-matched non-SIDS infants. The percentage of orexin immunoreactive neurons and the total number of neurons were quantified in the dorsomedial, perifornical and lateral hypothalamus at three levels of the tuberal hypothalamus. In the pons, the area of orexin immunoreactive fibres were quantified in the locus coeruleus (LC), dorsal raphe (DR), laterodorsal tegmental (LDT), medial parabrachial, dorsal tegmental (DTg) and pontine nuclei (Pn) using automated methods. OxA and OxB were co-expressed in all hypothalamic and pontine nuclei examined. In SIDS infants, orexin immunoreactivity was decreased by up to 21 % within each of the three levels of the hypothalamus compared to non-SIDS (p ≤ 0.050). In the pons, a 40-50 % decrease in OxA occurred in the all pontine nuclei, while a similar decrease in OxB immunoreactivity was observed in the LC, LDT, DTg and Pn (p ≤ 0.025). No correlations were found between the decreased orexin immunoreactivity and previously identified risk factors for SIDS, including prone sleeping position and cigarette smoke exposure. This finding of reduced orexin immunoreactivity in SIDS infants may be associated with sleep dysfunction and impaired arousal.

Cumulative effects of repetitive intermittent hypercapnic hypoxia on orexin in the developing piglet hypothalamus

“…The fornix itself was used as an indicator to divide the hypothalamus into the regions studied including: PeF, DMH, and LH. Similar to our previous studies using human tissue (Hunt et al, 2015a,b) confirmation of the three hypothalamic regions was achieved by an additional H&E‐stained section.…”

“…Quantitation was performed by the observer being blinded to the exposure regime, and conducted as previously reported to present the data as a percentage positive (Hunt et al, 2013, 2015a,b). ImageJ computer software (National Institutes of Health, USA) with the cell counter plug‐in was used for analyzing images.…”

A “Wear and Tear” Hypothesis to Explain Sudden Infant Death Syndrome

“…In the rostral ventrolateral medulla and PGCL, orexin receptors are expressed in sympathoexcitatory bulbospinal neurons (103). A significantly decreased orexin immunoreactivity in the hypothalamus and pontine nuclei was observed in SIDS infants (104). …”

Changes in orexinergic immunoreactivity of the piglet hypothalamus and pons after exposure to chronic postnatal nicotine and intermittent hypercapnic hypoxia

“…IHC for OxA and OxB was performed as in our previous studies (Hunt et al ., , ), with commercially available antibodies (Table S1) (OxA, Sc‐8070; OxB, Sc‐8071; Santa Cruz Biotechnology, Dallas, TX, USA). All reactions were performed at room temperature unless otherwise stated.…”