Paternal deprivation induces vigilance-avoidant behavior and accompanies sex-specific alterations in stress reactivity and central proinflammatory cytokine response in California mice (Peromyscus californicus).

RATIONALE: Early-life stress (ELS) can increase anxiety, reduce prosocial behaviors, and impair brain regions that facilitate emotional and social development. This knowledge greatly stems from assessing disrupted mother-child relationships, while studies investigating the long-term effects of father-child relationships on behavioral development in children are scarce. However, available evidence suggests that fathers may uniquely influence a child's behavioral development in a sex-specific manner. Rodent models examining mother-offspring interaction demonstrate relationships among ELS, neuroinflammatory mediators, and behavioral development; yet, the role paternal care may play in neuroimmune functioning remains unreported. OBJECTIVES: Using the biparental California mouse (Peromyscus californicus), we examined to what extent paternal deprivation impairs social and anxiety-like behaviors, augments peripheral corticosterone (CORT) response, and alters central proinflammatory cytokine production following an acute stressor in adulthood. METHODS: Biparentally reared and paternally deprived (permanent removal of the sire 24 h post-birth) adult mice were assessed for sociability, preference for social novelty, social vigilance, and social avoidance behaviors, followed by novelty-suppressed feeding (NSF) testing for general anxiety-like behavior. Following an acute stressor, circulating CORT concentrations and region-specific proinflammatory cytokine concentrations were determined via radioimmunoassay and Luminex multianalyte analysis, respectively. RESULTS: In response to a novel same-sex conspecific, social vigilance behavior was associated with reduced sociability and increased avoidance in paternally deprived mice-an effect not observed in biparentally reared counterparts. Yet, in response to a familiar same-sex conspecific, social vigilance persisted but only in paternally deprived females. The latency to consume during NSF testing was not significantly altered by paternal deprivation. In response to an acute physical stressor, lower circulating CORT concentrations were observed in paternally deprived females. Compared to control-reared males, paternal deprivation increased hypothalamic interleukin-1ß, but decreased hippocampal IL-6 protein concentration. CONCLUSION: Greater social vigilance behavior was demonstrated in paternally deprived mice while they avoided social interaction with a novel same-sex conspecific; however, in response to a familiar same-sex conspecific, paternal deprivation increased social vigilance behavior but only in females. It is possible that different neurobiological mechanisms underlie these observed behavioral outcomes as sex-specific central proinflammatory cytokine and stress responsivity were observed in paternally deprived offspring.

Sex-specific effects of neonatal paternal deprivation on microglial cell density in adult California mouse (Peromyscus californicus) dentate gyrus.

Adverse early-life experiences are risk factors for psychiatric disease development, resulting in stress-related neuronal modeling and neurobehavioral changes. Stressful experiences modulate the immune system, contributing to neuronal damage in higher cortical regions, like the hippocampus. Moreover, early-life stressors dysregulate the function of microglia, the resident immune cells of the brain, in the developing hippocampus. Paternal deprivation, an early-life stressor in many biparental species, facilitates sex-dependent inhibitions in hippocampal plasticity, but parental contributors to these sex-specific outcomes are unknown. Also, neurobiological mechanisms contributing to impairments in hippocampal neuroplasticity are less known. Thus, our goals were to 1) determine whether parental behavior is altered in maternal females following removal of the paternal male, 2) assess the effects of paternal deprivation on dentate gyrus (DG) volume and microglia proliferation, and 3) determine if early-life experimental handling mitigates sex-specific reductions in DG cell survival. California mice were born to multiparous breeders and reared by both parents (biparental care) or by their mother alone (i.e., father removed on postnatal day 1; paternal deprivation). One cohort of offspring underwent offspring retrieval tests for eight days beginning on postnatal day 2. On PND 68, these offspring (and a second cohort of mice without behavioral testing) were euthanized and brains visualized for bromodeoxyuridine (BrdU) and neuron-specific class III beta-tubulin (TuJ-1) or ionized calcium binding adaptor molecule 1 (Iba1). While mate absence did not impair maternal retrieval, paternal deprivation reduced DG volume, but Iba1+ cell density was only higher in paternally-deprived females. Neither sex or paternal deprivation significantly altered the number of BrdU+ or Tuj1+ cells in the DG - an absence of a reduction in cell survival may be related to daily handing during early offspring retrieval tests. Together, these data suggest that paternal deprivation impairs hippocampal plasticity; however, sex and early environment may influence the magnitude of these outcomes.

Racial and ethnic disparities in the pharmacologic management of diabetes mellitus among long-term care facility residents.

OBJECTIVE: To evaluate the prevalence of racial and ethnic disparities of antidiabetic treatment among residents of long-term care facilities in five states. RESEARCH DESIGN AND METHODS: Retrospective, cross-sectional study of 50,427 elderly nursing home residents with diabetes in New York, South Dakota, Kansas, Mississippi, and Ohio between 1993 and 1997. RESULTS: Thirty to fifty percent of residents received no antidiabetic medications. After adjusting for sociodemographic characteristics, comorbid conditions and diabetes severity, Blacks and Hispanics had lower rates of antidiabetic medication use than Whites, while Asians had slightly higher rates. For Native Americans the results were mixed, little disparity was seen when compared with Whites observed among New York nursing home residents, and while in South Dakota Native Americans had significantly lower rates of antidiabetic medication use than Whites. CONCLUSION: Although lack of information on glycemic control and non-medical treatments do not allow us to comment on quality of diabetes care, more research is needed to understand why some nursing homes residents are less likely to receive antidiabetic medication.