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Updated: Mar 28, 2026
Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Microglia modulate brainstem serotonergic expression following neonatal sustained hypoxia exposure: implications for
P M MacFarlane1, C A Mayer1, D G Litvin2
1Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, OH, 44106, USA.
Key Points:
Neonatal sustained hypoxia exposure modifies brainstem microglia and serotonin expression. The altered brainstem neurochemistry is associated with impaired ventilatory responses to acute hypoxia and mortality. The deleterious effects of sustained hypoxia exposure can be prevented by an inhibitor of activated microglia. These observations demonstrate a potential cause of the brainstem serotonin abnormalities thought to be involved in sudden infant death syndrome.
Abstract:
We showed previously that the end of the second postnatal week (days P11-15) represents a period of development during which the respiratory neural control system exhibits a heightened vulnerability to sustained hypoxia (SH, 11% O2 , 5 days) 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 immunoreactivity 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 immunoreactivity was prevented by minocycline (25 mg kg(-1) /2 days 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 aetiology of sudden infant death syndrome, 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.
Insights
Neonatal sustained hypoxia exposure alters brainstem serotonin and microglia, impairing breathing responses and increasing mortality. A microglia inhibitor prevented these effects, suggesting a link to sudden infant death syndrome.
Area of Science:
- Neuroscience
- Developmental Biology
- Respiratory Physiology
Background:
- The second postnatal week is a critical developmental period for respiratory control.
- Neonatal sustained hypoxia (SH) exposure during this period heightens vulnerability.
- Previous work indicated SH alters brainstem neurochemistry, impacting ventilatory control.
Purpose of the Study:
- To investigate if SH during the second postnatal week alters brainstem serotonin (5-HT) expression.
- To determine if microglia activity mediates these SH-induced changes.
- To assess if minocycline, a microglia inhibitor, can prevent SH-induced effects.
Main Methods:
- Rats were exposed to sustained hypoxia (11% O2 for 5 days) during the second postnatal week.
- Whole-body plethysmography assessed hypoxic ventilatory response (HVR).
- Brainstem tissue (nucleus of the solitary tract and dorsal motor nucleus of the vagus) was analyzed for microglia and 5-HT immunoreactivity.
Main Results:
- SH exposure attenuated HVR and increased mortality.
- SH increased microglia numbers and decreased 5-HT immunoreactivity in the nTS and DMNV.
- Minocycline treatment prevented the attenuated HVR, mortality, and neurochemical changes.
Conclusions:
- SH during a critical developmental window induces brainstem serotonin abnormalities.
- Microglia activation plays a key role in mediating the deleterious effects of SH.
- These findings suggest a potential mechanism linking neonatal hypoxia, brainstem changes, and sudden infant death syndrome.
