Ucp2 – natural-birth – hippocampus development
A report by Julia Simon-Areces et al., published in PLoS One indicates that natural (vaginal) birth but not Caesarian section birth in mice triggers uncoupling protein 2 (Ucp2) expression in hippocampal neurons.
The major finding of this study:
natural birth in mice triggers UCP2 expression in hippocampal neurons.
As discussed by the authors, the perinatal environment represents a critical period in brain development that determines the adult architecture of the central nervous system and related functions.
Mitochondrial Ucp2 is a critical determinant of fatty acid utilization by adult neurons and is involved in cell proliferation, neuroprotection and synaptogenesis in the adult brain. An important characteristic of breast milk, in contrast to placental blood support, is its high content of long chain fatty acids besides glucose.
In a previous work, published in Nature magazine, the authors have identified the mitochondrial uncoupling protein 2 (Ucp2) as a critical determinant of fatty acid utilization by adult neurons.
Specifically, the found that ghrelin initiates robust changes in hypothalamic mitochondrial respiration in mice that are dependent on uncoupling protein 2 (UCP2). Activation of this mitochondrial mechanism is critical for ghrelin-induced mitochondrial proliferation and electric activation of NPY/AgRP neurons, for ghrelin-triggered synaptic plasticity of pro-opiomelanocortin-expressing neurons, and for ghrelin-induced food intake.
Why uncoupling protein 2 induction is important for brain/hippocampus development?
Reviewing the literature, the authors of the PLoS One study address several studies showing that Ucp2 promotes scavenging of reactive oxygen species (ROS) in neurons, thus, most likely contributing for the promotion of dendritic growth and synaptogenesis. Of note, ROS are a critical negative regulator of hippocampal circuit development and, they are important contributors to neuronal lipid metabolism. Uncoupling protein 2 is also implicated in protection of adult as well as developing neurons in a febrile seizure model in rats at a time of breastfeeding.
In the PLoS One study, Julia Simon-Areces and colleagues from the Cajal institute in Spain; the Federal University of Rio Grande do Sul, Brazil, and the Yale University School of Medicine, US investigated the Ucp2 induction in the hippocampus perinatally, and the Ucp2-associated cellular mechanisms involved in the development of neuronal circuits in vitro with implications for adult behavior.
Uncoupling protein 2 mRNA levels were induced in newborns by vaginal birth, and significantly higher level of Ucp2 protein expression was observed at the day of delivery in animals that were born via vaginal birth compared to those with Cesarean section.
In naturally born mice, uncoupling protein 2 protein remained elevated early postnatally, as well as in adulthood. According to the authors, their findings are consistent with previous reports indicating beneficial effects of Ucp2 and high fat content of breast milk, related to protection of febrile seizures in early postnatal animals. The authors suggest that Ucp2 mRNA induction may be associated with hypoxia/ischemia that accompanies vaginal birth.
Furthermore, the authors discuss that Ucp2 activity neutralizes ROS, thus allowing continuous CPT1-promoted fatty acid oxidation and transcription of genes promoting mitochondrial proliferation. This, according to the investigators enables continuous support of the bioenergetics needs of sustained neuronal firing and synaptic plasticity. And, importantly, this intracellular signaling should be supportive of neuronal activation and decreased vulnerability of neurons to cellular stress in any region where they are activated.
The authors conclude, quote: “These data reveal a critical role for Ucp2 expression in the development of hippocampal neurons and circuits and hippocampus-related adult behaviors”. Also, the induction of Ucp2 by birth -associated physiological stress enables metabolic adaptation to a switch available nutrient utilization that is critical for proper survival and development of hippocampal and other brain neurons.
In many countries Caesarian sections are performed in more than 30% of all births. This report is probably among the first to address and study in details, in experimental conditions, a possible relationship between natural birth and brain development.
As per another PLoS One 2016 study Caesarean section (CS) rates continue to evoke worldwide concern because of their steady increase, lack of consensus on the appropriate CS rate and the associated additional short- and long-term risks and costs. Latin America and the Caribbean region has the highest CS rates (40.5%), followed by Northern America (32.3%), Oceania (31.1%), Europe (25%), Asia (19.2%) and Africa (7.3%).
SOURCE: PLoS One, 2012, 7(8):e42911. Epub 2012 Aug 8
