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.
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Abbreviations
- DMH:
-
Dorsomedial hypothalamus
- DR:
-
Dorsal raphe
- DTg:
-
Dorsal tegmental nucleus
- LH:
-
Lateral hypothalamus
- LDT:
-
Laterodorsal tegmental nucleus
- LC:
-
Locus coeruleus
- MPB:
-
Medial parabrachial nucleus
- Ox:
-
Orexin
- OxA:
-
Orexin A
- OxB:
-
Orexin B
- PPT:
-
Pedunculopontine tegmental area
- PeF:
-
Perifornical area
- Pn:
-
Pontine nucleus
- PPO:
-
Prepro-orexin
- REM:
-
Rapid eye movement
- URTIs:
-
Upper respiratory tract infections
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Acknowledgments
The tissue used in this study was provided by the NSW Forensic and Analytical Science Service. The authors acknowledge the facilities, and scientific and technical assistance of the Australian Microscopy and Microanalysis Research Faculty at the Australian Centre of Microscopy and Micro Analysis, University of Sydney. Research funded by the SIDS Stampede, Australia, and the Miranda Bradshaw Foundation.
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Hunt, N.J., Waters, K.A., Rodriguez, M.L. et al. Decreased orexin (hypocretin) immunoreactivity in the hypothalamus and pontine nuclei in sudden infant death syndrome. Acta Neuropathol 130, 185–198 (2015). https://doi.org/10.1007/s00401-015-1437-9
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DOI: https://doi.org/10.1007/s00401-015-1437-9