Altered Development of Mesencephalic Dopaminergic Neurons in SIDS: New Insights into Understanding Sudden Infant Death Pathogenesis

Abstract

Sudden infant death syndrome (SIDS) is defined as the unexpected sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation. The SIDS pathogenesis is still unknown; however, abnormalities in brain centers that control breathing and arousal from sleep, including dramatic changes in neurotransmitter levels, have been supposed in these deaths. This is the first study focusing on mesencephalic dopaminergic neurons, so far extensively studied only in animals and human neurological diseases, in SIDS. Dopaminergic structures in midbrain sections of a large series of sudden infant deaths (36 SIDS and 26 controls) were identified using polyclonal rabbit antibodies against tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, and the dopamine transporter, a membrane protein specifically expressed in dopaminergic cells. Dopamine-immunolabeled neurons were observed concentrated in two specific structures: the pars compacta of the substantia nigra and in the subnucleus medialis of the periaqueductal gray matter. Anatomical and functional degenerations of dopaminergic neurons in these regions were observed in most SIDS cases but never in controls. These results indicate that dopamine depletion, which is already known to be linked especially to Parkinson’s disease, is strongly involved even in SIDS pathogenesis.

Sudden Infant Death Syndrome, Pulmonary Edema, and Sodium Toxicity: A Grounded Theory

“…In addition to high sodium levels, cow milk is much higher in phosphorus than breast milk, and excessive dietary phosphate has been linked to degeneration of dopaminergic neurons [ 73 ]. Coincidently, a recent study found degeneration of dopaminergic neurons in the majority of 36 SIDS cases, compared to no effect in control infants [ 74 ], a finding that is concordant with harm in SIDS from cow milk consumption. Infants’ exposure to excessive minerals in cow milk and other solid foods with potential risk associated with sodium toxicity and SIDS can be reduced by recommendation of exclusive breastfeeding during the first six months after birth, as advised by the American Academy of Pediatrics [ 75 ] and the World Health Organization [ 76 ].…”

Involvement of the Superior Colliculus in SIDS Pathogenesis

“…This failure to respond in the presence of a hypoxic challenge can lead to SIDS [ 11 , 12 ]. In fact, numerous studies have demonstrated the association between morphological and/or functional alterations of the brainstem centers that regulate breathing/hypoxemia responses and SIDS [ 13 , 14 , 15 , 16 , 17 , 18 ].…”