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1.
Transl Psychiatry ; 5: e606, 2015 Jul 21.
Article in English | MEDLINE | ID: mdl-26196439

ABSTRACT

Genes and social experiences interact to create variation in social behavior and vulnerability to develop disorders of the social domain. Socially monogamous prairie voles display remarkable diversity in neuropeptide receptor systems and social behavior. Here, we examine the interaction of early-life adversity and brain oxytocin receptor (OTR) density on adult social attachment in female prairie voles. First, pups were isolated for 3 h per day, or unmanipulated, from postnatal day 1-14. Adult subjects were tested on the partner preference (PP) test to assess social attachment and OTR density in the brain was quantified. Neonatal social isolation impaired female PP formation, without affecting OTR density. Accumbal OTR density was, however, positively correlated with the percent of time spent huddling with the partner in neonatally isolated females. Females with high accumbal OTR binding were resilient to neonatal isolation. These results are consistent with the hypothesis that parental nurturing shapes neural systems underlying social relationships by enhancing striatal OTR signaling. Thus, we next determined whether early touch, mimicking parental licking and grooming, stimulates hypothalamic OT neuron activity. Tactile stimulation induced immediate-early gene activity in OT neurons in neonates. Finally, we investigated whether pharmacologically potentiating OT release using a melanocortin 3/4 agonist, melanotan-II (10 mg kg(-1) subcutaneously), would mitigate the social isolation-induced impairments in attachment behavior. Neonatal melanotan-II administration buffered against the effects of early isolation on partner preference formation. Thus, variation in accumbal OTR density and early OT release induced by parental nurturing may moderate susceptibility to early adverse experiences, including neglect.


Subject(s)
Animals, Newborn/psychology , Arvicolinae/physiology , Oxytocin/physiology , Social Behavior , Social Isolation , Animals , Animals, Newborn/physiology , Arvicolinae/psychology , Female , Gene Expression/physiology , Object Attachment , Peptides, Cyclic/pharmacology , Receptors, Melanocortin/antagonists & inhibitors , Receptors, Oxytocin/physiology , Resilience, Psychological , Social Isolation/psychology , Vasopressins/physiology , alpha-MSH/analogs & derivatives , alpha-MSH/pharmacology
2.
Mater Sci Eng C Mater Biol Appl ; 42: 587-94, 2014 Sep.
Article in English | MEDLINE | ID: mdl-25063157

ABSTRACT

The internal mechanical property characteristics as functions of position and degradation time of PLGA(50:50)-αTCP nanocomposites of varying ceramic-polymer ratios degraded in an aqueous medium have been assessed using depth-sensing nanoindentation. The addition of nanoparticulate αTCP increases the elastic modulus of undegraded specimens from 3.72 ± 0.12 GPa for pure PLGA(50:50) samples to 7.23 ± 0.16 GPa recorded for undegraded 40 wt.% TCP nanocomposites. Additionally αTCP incorporation decreases the viscoelastic loss tangent from 0.189 ± 0.040 measured for pure undegraded PLGA(50:50) to an average of 0.091 ± 0.006 for undegraded ceramic-polymer composites. No variation in viscosity for the composites with ceramic loading was evidenced. The stiffening effect of αTCP addition closely conforms to the lower Hashin-Shtrikman bounds demonstrating that an evenly dispersed nano-filler is the least amenable ceramic configuration to enhance the mechanical properties of PLGA-αTCP nanocomposites. The mechanical property evolution for all composite types in an aqueous degradation medium is dominated by material hydration which effects reduced material stiffness and increased specimen viscosity generating a core-periphery mechanical property distribution in terms of elastic modulus and viscoelastic phase angle. The mechanical property core-periphery structure correlates strongly with the core-periphery density structure characterized using X-ray microtomography. Hydrated regions exhibit significant reductions in elastic modulus and viscosity increases which are typical of elastomers.


Subject(s)
Calcium Phosphates/chemistry , Lactic Acid/chemistry , Nanocomposites/chemistry , Nanotechnology/methods , Polyglycolic Acid/chemistry , Elastic Modulus , Polylactic Acid-Polyglycolic Acid Copolymer , Viscosity
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