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Kenkel, W. M.

Publications and source records attributed to Kenkel, W. M..

2 recordsLinked to original sources

Oxytocin and Vasopressin at Birth Prevent Hypoactivity and Excess Weight Gain in Vole Offspring Delivered by Cesarean Section

Birth occurs during a sensitive period in brain development wherein hormones facilitate the dramatic shift in physiology that accomplishes the transition to extrauterine homeostasis. The surge in birth signaling hormones is abridged in cases of delivery by cesarean section (CS), which accounts for 32% of all births in the U.S. Epidemiological studies have associated birth via CS with increased risk of obesity in later life. Here, we sought to investigate this association using an experimental preclinical animal model, the prairie vole. Subjects were delivered either via vaginal delivery (VD) or CS and then cross-fostered. CS delivery led to increased body weight across development, which could be prevented with hormone rescue of oxytocin (OXT) and arginine vasopressin (AVP), delivered to neonates immediately after CS. This weight gain could not be attributed to differences in birth weight, parenting, food consumption, or thermoregulation; however, CS subjects moved slower than VD subjects, which hormone rescue reversed. Hormone rescue also reduced adiposity in adulthood among CS subjects. The dopamine system was dysregulated in the caudate/putamen of CS offspring, suggesting a neural mechanism for the decreased locomotion. Hormone rescue of CS neonates restored dopamine synthesis in the caudate/putamen and increased spontaneous locomotor activity. These findings suggest CS can lead to increased weight gain in part through a reduction of locomotion driven by long-lasting changes in striatal dopamine regulation, all of which can be prevented by treating CS neonates with a single peripheral administration of two birth-signaling hormones, OXT and AVP.

neuroscience↗

Impact of Cesarean Delivery on Reward Behavior and Neurodevelopment in Adult Prairie Vole Offspring

Accumulating clinical evidence has shown that birth by Cesarean section (CS) is associated with a higher incidence of disorders involving the dysregulation of dopamine (DA), such as attention deficit-hyperactivity disorder, autism spectrum disorder, and obesity, compared to vaginal delivery (VD). The mesolimbic (ML) system encompasses DAergic neurons that modulate reward processes underlying learning, motivation, and food intake. Previous research has shown that there are lower levels of DA in the prefrontal cortex and higher in the nucleus accumbens (NAc) of CS offspring. Alterations in the ML-DA system as a consequence of birth via CS may impact behavioral response to rewarding stimuli, such as food. Thus, we aimed to ascertain the behavioral and neurodevelopmental outcomes relevant to food reward in CS prairie vole offspring. This study utilized conditioned place preference (CPP) testing to assess learning using context-dependent conditioning, operant conditioning to assess acquisition of a conditioned response and motivation to receive a reinforcer, and immunohistochemistry (IHC) to stain for tyrosine hydroxylase (TH) in the NAc. Behavioral results showed no difference in preference for the conditioned chamber during CPP testing between CS offspring and their VD counterparts. CS prairie vole offspring had a lower average break point during progressive-ratio testing compared to VD offspring, but no difference in response during fixed-ratio 1 or 3 testing. IHC results showed CS offspring had lower levels of TH-immunoreactivity in the NAc core and shell. These findings further support that delivery by CS has long-term neurodevelopmental effects, specifically in the brains reward system, and that CS offspring have decreased motivation toward food reward independent of deficits in learning.

neuroscience↗