Biology subjects

Hyatt, K.

Publications and source records attributed to Hyatt, K..

3 recordsLinked to original sources

bioRxiv2021

Oxytocin Signaling Regulates the Homeostatic Response to Cold Stress in Poikilothermic Vertebrates

When exposed to low temperature, homeothermic vertebrates maintain internal body temperature by activating thermogenesis and by altered metabolism, synchronized by neuroendocrine responses. Although such physiological responses also occur in poikilothermic vertebrates, the prevailing notion is that their reactions are passive. Here, we explored molecular hypothalamic and physiological responses to cold stress in the tropical poikilotherm Nile tilapia (Oreochromis niloticus). We show that cold exposed tilapia exhibit complex homeostatic responses, including increased hypothalamic oxytocin, plasma glucose and cortisol concomitant with reduced plasma lactate and metabolic rate. Pharmacological or genetic blockage of oxytocin signaling further affected metabolic rate in two cold-exposed poikilothermic models. This indicates that oxytocin, a known thermoregulator in homeotherms, actively regulates temperature-related homeostasis in poikilotherms. Overall, our findings show that the brain of poikilotherms actively responds to cold temperature by regulating metabolic physiology. Moreover, we identify oxytocin signaling as an adaptive and evolutionarily conserved metabolic regulator of temperature-related homeostasis.

physiology↗

bioRxiv2020

MATERNAL ZIKA VIRUS (ZIKV) INFECTION FOLLOWING VAGINAL INOCULATION WITH ZIKV-INFECTED SEMEN IN THE TIMED-PREGNANT OLIVE BABOON

ZIKV infection is associated with pregnancy loss, fetal microcephaly and other malformations. While Aedes sp. of mosquito are the primary vector for ZIKV, sexual transmission of ZIKV is a significant route of infection. ZIKV has been documented in human, mouse and non-human primate (NHP) semen. It is critical to establish NHP models of vertical transfer of ZIKV that recapitulate human ZIKV pathogenesis. We hypothesized that vaginal deposition of ZIKV infected baboon semen would lead to maternal infection and vertical transfer in the olive baboon (Papio anubis). Timed pregnant baboons (n=6) were inoculated via vaginal deposition of baboon semen containing 106 ffu ZIKV (n=3, French Polynesian isolate:H/PF/2013, n=3 Puerto Rican isolate:PRVABC59) at mid-gestation (86-95 days gestation [dG]; term 183dG) on day (d) 0 (all dams), and then at 7 day intervals through three weeks. Maternal blood, saliva and cervico-vaginal washes were obtained at select days post-inoculation. Animals were euthanized at 28 days post initial inoculation (dpi; n=5) or 39 dpi (n=1) and maternal/fetal tissues collected. vRNA was quantified by qPCR. Viremia was achieved in 3/3 FP ZIKV infected dams and 2/3 PR ZIKV. ZIKV RNA was detected in cvw (5/6 dams;). ZIKV RNA was detected in lymph nodes, but not ovary, uterus, cervix or vagina in the FP ZIKV dams but was detected in uterus, vagina and lymph nodes. Placenta, amniotic fluid and all fetal tissues were ZIKV RNA negative in the FP infected dams whereas 2/3 PR infected dam placentas were ZIKV RNA positive. We conclude that ZIKV infected semen is a means of ZIKV transmission during pregnancy in primates. The PR isolate appeared more capable of wide spread dissemination to tissues, including placenta compared to the FP strain. IMPORTANCEDue to its established link to pregnancy loss, microcephaly and other major congenital anomalies, Zika virus (ZIKV) remains a worldwide health threat. Although mosquitoes are the primary means of ZIVK transmission, sexual transmission in human populations is well documented and provides a means for widespread dissemination of the virus. Differences in viremia, tissue distribution, immune responses and pregnancy outcome from sexually transmitted ZIKV compared to the subcutaneous route of infection are needed to better clinically manage ZIKV in pregnancy. Through our previous work, we have developed the olive baboon as a non-human primate model of ZIKV infection that is permissible to ZIKV infection via the subcutaneous route of inoculation and transfer of ZIKV to the fetus in pregnancy. The current study evaluated the course of ZIKV infection after vaginal inoculation of ZIKV in pregnant baboons at mid-gestation using baboon semen as the carrier and comparing two isolates of ZIKV, the French Polynesian isolate first associated with microcephaly and the Puerto Rican isolate, associated with an increased risk of microcephaly observed in the Americas.

physiology↗

bioRxiv2018

ZIKA VIRUS INFECTION AT MID-GESTATION RESULTS IN FETAL CEREBRAL CORTICAL INJURY AND FETAL DEATH IN THE OLIVE BABOON.

Zika virus (ZIKV) infection during pregnancy in humans is associated with an increased incidence of congenital anomalies including microcephaly as well as fetal death and miscarriage and collectively has been referred to a Congenital Zika Syndrome (CZS). Animal models for ZIKV infection in pregnancy have been developed including mice and macaques. While microcephaly has been achieved in mice via direct injection of ZIKV into the fetal brain or via interference with interferon signaling, in macaques the primary fetal CZS outcome are ocular defects. In the present study we develope the olive baboon (Papio anubis), as a model for the vertical transfer of ZIKV during pregnancy. We infected four mid-gestation, timed-pregnant baboons with the French Polynesian ZIKV isolate (104 ffu) and examined the acute phase of vertical transfer by stopping the study of one dam at 7 days post infection (dpi), two at 14 dpi and one at 21 dpi. All dams exhibited mild to moderate rash and conjunctivitis; three of four dams exhibited viremia at 7 dpi. Of the three dams studied to 14 to 21 days, only one still exhibited viremia on day 14. Vertical transfer of ZIKV to the fetus was found in two pregnancies; in one, vertical transfer was associated with fetal death at [~]14 dpi. In the other, vertical transfer was observed at 21 dpi. Both fetuses had ZIKV RNA in the fetal cerebral cortex as well as other tissues. The 21 dpi fetal cerebral cortex exhibited notable defects in radial glia, radial glial fibers, loss and or damage of immature oligodendrocytes and a loss in neuroprogenitor cells (NPCs). In addition, indices of pronounced neuroinflammation were observed including astrogliosis, increased microglia and IL-6 expression. The dams studied to 14 dpi (n=2) and 21 dpi (n=1) exhibited a anti-ZIKV IgM response and IgG response (21 dpi) that included transfer of the IgG to the fetal compartment (cord blood). The severity of systemic inflammatory response (cytokines and chemokines) reflected the vertical transfer of ZIKV in the two pregnancies. As such, these events likely represent the early mechanisms that lead to microcephaly and/or other CNS pathologies in a primate infected with ZIKV and are the first to be described in a non-human primate during the acute phase of ZIKV infection with a contemporaneous ZIKV strain. The baboon thus represents a major NHP for advancing as a model for ZIKV induced brain pathologies to contrast and compare to humans as well as other NHPs such as macaques.\n\nAUTHOR SUMMARYZika virus is endemic in the Americas, primarily spread through mosquitos and sexual contact. Zika virus infection during pregnancy in women is associated with a variety of fetal pathologies now referred to as Congenital Zika Syndrome (CZS), with the most severe pathology being fetal microcephaly. Developing model organisms that faithfully recreate Zika infection in humans is critical for future development of treatments and preventions. In our present study, we infected Olive baboons at mid-gestation with Zika virus and studied the acute period of viremia and transfer of Zika virus to the fetus during the first three weeks after infection to better understand the timing and mechanisms leading to CZS. We observed Zika virus transfer to fetuses resulting in fetal death in one pregnancy and in a second pregnancy, significant damage to the frontal cortex of the fetal brain consistent with development of microcephaly, closely resembling infection in pregnant women. Our baboon model differs from macaque non-human primate models where the primary fetal outcome during pregnancy following infection with contemporary strains of Zika virus is ocular pathology. Thus, the baboon provides a promising new non-human primate model to further compare and contrast the consequences of Zika virus infection in pregnancy to humans and macaques to better understand the disease.

neuroscience↗