Microglia modulate brainstem serotonergic expression following neonatal sustained hypoxia exposure: implications for Sudden Infant Death Syndrome

Abstract

We showed previously that the end of the second postnatal week (P11-15 days) represents a period of development during which the respiratory neural control system exhibits a heightened vulnerability to sustained (SH, 11% O₂, 5 days) hypoxia exposure. In the current study, we investigated whether the vulnerability to SH during the same developmental time period is associated with changes in brainstem serotonin (5-HT) expression and whether it can be prevented by the microglia inhibitor, minocycline. Using whole-body plethysmography SH attenuated the acute (5 min) hypoxic ventilatory response (HVR) and caused a high incidence of mortality compared to normoxia rats. SH also increased microglia cell numbers and decreased 5-HT immuno-reactivity in the nucleus of the solitary tract (nTS) and dorsal motor nucleus of the vagus (DMNV). The attenuated HVR, mortality, and changes in nTS and DMNV immuno-reactivity was prevented by minocycline (25 mg kg⁻¹/2days during SH). These data demonstrate that the 5-HT abnormalities in distinct respiratory neural control regions can be initiated by prolonged hypoxia exposure and may be modulated by microglia activity. These observations share several commonalities with the risk factors thought to underlie the etiology of Sudden Infant Death Syndrome (SIDS), including: 1) a vulnerable neonate; 2) a critical period of development; 3) evidence of hypoxia; 4) brainstem gliosis (particularly the nTS and DMNV); and 5) 5-HT abnormalities.

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