| Along with the acceleration of social modernization,the phenomenon of absence of parental companionship in childhood is becoming more and more serious.The impact of lack of companionship on children's adult social behavior has gradually become a social problem.Parent-child relationships play an important to promote offspring healthy growth and development.Early life stress is thought to increase the risk for adult psychiatric disorders(anxiety,depression,substance and alcohol abuse,hyperactive stress physiology,and others).Attachment is a reciprocal connection between caregivers and child.In childhood,infants display attachment to their parents including physical attachment and emotional attachment.Once the baby's born,they are mainly based on physiological attachment.With the maturity of physiological function,the attachment of infants to their parents is dominated by emotion.In human,some parents provide adequate material support to their children,but they ignore the children's emotional needs.This form of emotional neglect is associated with a marked increase in vulnerability to abnormal social behaviors including early pregnancy,fighting,drug addiction,even to commit crimes.Whether the disruption of emotional attachment affects emotional and social behaviors remains unexplored.Although extensively research has focused on the effects of early life stress using only maternal separation or deprivation because of the limitation of animal models,the disruption of father-infant relationship impact on offspring is still unclear.This study using socially monogamous mandarin vole,to explore pre-weaning paternal deprivation on mood and social behaviors and its underlying mechanism will scientifically guide to guarantee physiological and behavioral health of mammal offspring including human.Part 1:Emotional attachment of pre-weaning pups to mothers and fathers in mandarin voles.In rodents,studies into the effects of maternal and paternal deprivation on the brain and behavior are traditionally done on animals from postnatal day 0 to 14 when parents display high levels of licking and grooming.Deprivation experiments that reveal attachment conducted during this period(postnatal day 1 to 21)are confounded because physiological and emotional deprivation occur simultaneously.Whether rodent pups of greater physiological independence from postnatal 14 to 21 days show emotional attachment towards mothers and fathers remains unclear.Here we establish a new animal model for attachment experiments in animals 14 to 21 days old using monogamous mandarin voles(Microtus mandarinus).Levels of emotional attachment of pups from postnatal 14 to 21 days were measured using preference tests.Pups spent more time in contact with their mothers,more time approaching,sniffing,climbing and walking near their mothers,and emitted more calls on their mother's side compared to an unknown female.They also showed a preference for their fathers over an unknown male.When mothers and fathers were presented simultaneously,pups increased number of vocalization near their mother.Pups also showed a very clear preference for their mother as they spent more time near her than near their father.The durations that pups spent in approach,sniff,climbing,inactivity and walking were increased near their mother.The relative time pups spent in contact with mothers did not vary from PND 14 to 21.However,this parameter showed presented the gradual step-down trend for the time spent in contact with fathers.These results suggested that that PND 14 to 21 mandarin vole pups have high levels of emotional attachment to their mothers and fathers.Mandarin voles can be used as a model to explore the effects of disruption of early emotional attachment on the adult emotion and social behaviors and underlying its neuroendocrine mechanisms.Part 2:The involvement of oxytocin system in the medial prefrontal cortex in effects of pre-weaning paternal deprivation on anxiety-like behavior and social preference in adult mandarin voles.Early adverse experiences often produce devastating consequences on adult emotion and social behaviors.Effects of neonatal paternal deprivation on behaviors and brain have been found because pups receive intense licking and grooming and other paternal care with physiological and emotional attachments on fathers.The pups display complete fur and thermoregulatory ability during pre-waning period(postnatal day 14 to 21)possibly with more emotional attachment to fathers,whether paternal deprivation during pre-weaning period affects brain and behaviors and its underlying mechanisms remains unclear.The neuropeptide,oxytocin(OT),can modulate emotion and social behaviors.Thus,we examine the involvement of OT system on effects of pre-weaning paternal deprivation(PD)on anxiety-like behaviors and social preference using socially monogamous mandarin voles.Pups were deprived of fathers during postnatal day 14 to 21.At adult,they were tested on the open field and social preference to assess emotion and sociability.The change in OT-immunoreactive fibers,paraventricular nucleus OT positive neurons,medial prefrontal cortex(mPFC)OT receptor(OTR)and Vasopressin 1a receptor(V1aR)protein.In addition,behavioral effects of micro-infusion of OT or OT plus OT receptor antagonist into mPFC were evaluated in adult mandarin voles with PD.Levels of emotional attachment of pups from postnatal 14 to 21 days were measured using preference tests.Pups spent more time in contact with their mothers,more time approaching,sniffing,climbing and walking near their mothers,and emitted more calls on their mother's side compared to an unknown female.They also showed a preference for their fathers over an unknown male.While pups displayed attachment to both their mothers and fathers,levels directed towards mothers were higher in tests when mothers and fathers were presented simultaneously.We found that PD increased anxiety-like behavior and attenuated social preference in adult males and females;reduced the number of c-fos positive labeled neurons in the medial prefrontal cortex(mPFC)and nucleus accumbens shell,decreased the the percentage of c-fos/OT-labeled cells in the paraventricular nucleus after the social approach test,but PD did not affect c-fos expression of the Nacc core in both of sex;decreased prelimbic cortex OT-immunoreactive fibers and paraventricular nucleus OT positive neurons;reduced levels of the mPFC OT receptor protein in females and OT receptor and V1a receptor protein in males.Intra-prelimbic cortical OT injections reversed anxiety-like behavior and social preferences affected by PD,whereas injections of OT and OT receptor antagonist blocked this reversal.These findings demonstrate that pre-weaning paternal deprivation lead to increrased anxiety-like behavior and attenuated social preference with involvement of mPFC OT system.Part 3:Pre-weaning paternal deprivation impairs social recognition and alters hippocampal neurogenesis and spine density in adult mandarin voles.Disruptions of the early social environment,such as maternal separation or early deprivation,can impair cognitive function,alter offspring neurogenesis and restrict dendritic architecture in the hippocampus.However,whether paternal deprivation during the pre-weaning period affects adult neurogenesis,synaptogenesis and social recognition remains unclear in monogamous species.In the present study,mandarin voles pups were deprived of fathers during postnatal day 14 to 21.Then social recognition,hippocampal neurogenesis and spine density,basal levels of corticosterone(CORT)and OT were examined at adulthood.We found that PD impaired social recognition at adulthood.In addition,5-bromo-2-deoxyuidine(BrdU)immunoreactive cells and Brdu/Neun-labeled cells in the dentate gyrus were reduced by PD in females,but not in males.Double-staining with BrdU and the immature neuron marker DCX demonstrated that PD reduced neurogenesis both in male and female voles.PD also decreased the number of dendritic spines in the dentate gyrus at adulthood.PD reduced circulating levels of OT and increased CORT only in females.These findings suggest that PD can also contribute to altered neurogenesis,spine density of the hippocampus and serum endocrine parameters.Taken together,these results indicate that mandarin voles can be used as an animal model to investigate the effects of early emotional attachment disruption on the adult brain and behavior.PD leads to increased anxiety-like behavior and attenuated social preferences with involvement of the mPFC OT system.The prelimbic cortex OT system may be an important target for the treatment of disorders related to early adverse experiences.These results demonstrated that abnormal social recognition induced by PD may be linked with alterations in neurogenesis and spine density of the dentate gyrus and levels of OT and CORT. |
PDF Full Text Request