Changes in Neuroactive Steroid Concentrations After Preterm Delivery in the Guinea Pig

Kelleher, Meredith A.; Hirst, Jonathan J.; Palliser, Hannah K.

doi:10.1177/1933719113485295

Cited by 35 publications

(85 citation statements)

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“…Additionally, the results indicate that there are sex differences in the influences of prematurity on these parameters, with males seemingly more affected by early delivery. Furthermore, one of the most important findings was that the deficiencies in neurodevelopment of ex-preterm males seen previously in neonates remained until juvenility, whereas females were able to restore their initial reductions (25,26). Our previous studies in guinea pigs showed markers of mature oligodendrocytes were reduced in preterm compared to term gestational age fetuses, and were markedly affected by preterm delivery in the neonatal hippocampus and subcortical white matter in both sexes (25,26).…”

Section: Discussionmentioning

confidence: 83%

“…Furthermore, one of the most important findings was that the deficiencies in neurodevelopment of ex-preterm males seen previously in neonates remained until juvenility, whereas females were able to restore their initial reductions (25,26). Our previous studies in guinea pigs showed markers of mature oligodendrocytes were reduced in preterm compared to term gestational age fetuses, and were markedly affected by preterm delivery in the neonatal hippocampus and subcortical white matter in both sexes (25,26). The use of an ex-preterm juvenile model in the present study allowed us to ascertain whether oligodendrocyte expression remains affected until childhood, when many of the school-related disabilities become apparent clinically.…”

Section: Discussionmentioning

confidence: 92%

mentioning

confidence: 90%

“…Our previous studies have demonstrated a dramatic drop in brain allopregnanolone concentrations following birth at term and preterm compared to fetal levels (26). This reduced allopregnanolone-mediated neuroprotection increases the vulnerability of the neonatal brain to insults such as hypoxia.…”

mentioning

confidence: 93%

“…This reduced allopregnanolone-mediated neuroprotection increases the vulnerability of the neonatal brain to insults such as hypoxia. Furthermore, these preterm animals also show decreased myelination in the CA1 region of the hippocampus and the adjacent subcortical white matter 24 h after delivery, and in the cerebellum at term equivalence (25)(26)(27).In this study, we examined the effect of preterm birth on brain development, focusing on the mature myelinating oligodendrocytes and reactive astrocytes that are essential for proper neuronal circuitry and synaptic transmission, to identify effects at adolescence in guinea pigs. We also aimed to ascertain the impact that preterm delivery has on the expression of neurosteroid-sensitive GABA A receptor subunits, in addition to behavior at juvenility, with a particular focus on the hyperactive and anxious behaviors that are common to ex-preterm males and females respectively.…”

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confidence: 99%

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Long-term effects of preterm birth on behavior and neurosteroid sensitivity in the guinea pig

et al. 2016

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Background: Ex-preterm children and adolescents are at risk of developing late-onset neurodevelopmental and behavioral disorders. The mechanisms by which this happens are poorly understood and relevant animal models are required. Methods: Ex-preterm (delivered at 62 d gestation) and term (spontaneously delivered) juvenile guinea pigs underwent behavioral testing at 25 d corrected postnatal age, with tissues collected at 28 d. Neurodevelopmental markers (myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP)) were analyzed in the hippocampus and subcortical white matter by immunohistochemistry. Gamma-aminobutyric acid A (GABA A ) receptor subunit mRNA levels were quantified by reverse transcription polymerase chain reaction (RT-PCR), and salivary cortisol measured by enzyme-linked immunosorbent assay. results: Preterm males travelled greater distances, were mobile for longer, spent more time investigating objects, and approached or interacted with familiar animals more than controls. Myelination and reactive astrocyte coverage was lower in the hippocampus and the subcortical white matter in preterm males. Hippocampal levels of the α5 subunit were also lower in the preterm male brain. Baseline salivary cortisol was higher for preterm males compared to controls. conclusion: We conclude that juvenile ex-preterm male guinea pigs exhibit a hyperactive phenotype and feature impaired neurodevelopment, making this a suitable model for future therapeutic studies. c hildren born preterm (birth at <37 wk gestation) have an increased risk of developing a long-term neurodevelopmental disability (1,2). Importantly, this risk exists even in those thought to be "well" at the time of discharge from neonatal care and in those with no evidence of the structural brain injuries known to be associated with adverse neurodevelopmental outcomes (e.g., intraventricular hemorrhage or periventricular leukomalacia) (3,4). Thus, although intraventricular hemorrhage and, or, periventricular leukomalacia explain neurodevelopmental problems in a subset of high-risk infants, they do not account for the overall burden of neurodisability seen in the ex-preterm population.Although major neurodevelopmental problems are usually picked up early, subtle behavioral or psychiatric disorders may not become apparent until school age, at a time distant from the causative insult (5,6). Anxiety disorder and attention deficit hyperactivity disorder are the most commonly diagnosed disorders in school-aged ex-preterm children (7,8). Attention deficit hyperactivity disorder has a male preponderance and is characterized by a deficit in behavioral inhibition, inattention, impulsivity and social difficulties, whereas anxiety disorder is more commonly diagnosed in ex-preterm females (7,8). Thus, the behavioral outcomes of preterm birth occur in a sex-dependent manner. Other neuropathologies, including depression, and impaired cognitive performance are also increased in those born preterm compared to children and adolescents born at term (5,9-11). Hypo-m...

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