myelin-basic-protein and Birth-Weight

Preterm birth is a major cause of neurodevelopmental disorders. Allopregnanolone, a key metabolite of progesterone, has neuroprotective and developmental effects in the brain. The objectives of this study were to measure the neuroactive steroid concentrations following preterm delivery in a neonatal guinea pig model and assess the potential for postnatal progesterone replacement therapy to affect neuroactive steroid brain and plasma concentrations in preterm neonates.. Preterm (62-63 days) and term (69 days) guinea pig pups were delivered by cesarean section and tissue was collected at 24 hours. Plasma progesterone, cortisol, allopregnanolone, and brain allopregnanolone concentrations were measured by immunoassay. Brain 5α-reductase (5αR) expression was determined by Western blot. Neurodevelopmental maturity of preterm neonates was assessed by immunohistochemistry staining for myelination, glial cells, and neurons.. Brain allopregnanolone concentrations were significantly reduced after birth in both preterm and term neonates. Postnatal progesterone treatment in preterm neonates increased brain and plasma allopregnanolone concentrations. Preterm neonates had reduced myelination, low birth weight, and high mortality compared to term neonates. Brain 5αR expression was also significantly reduced in neonates compared to fetal expression.. Delivery results in a loss of neuroactive steroid concentrations resulting in a premature reduction in brain allopregnanolone in preterm neonates. Postnatal progesterone therapy reestablished neuroactive steroid levels in preterm brains, a finding that has implications for postnatal growth following preterm birth that occurs at a time of neurodevelopmental immaturity.

Topics: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase; Animals; Animals, Newborn; Birth Weight; Brain; Disease Models, Animal; Female; Gestational Age; Glial Fibrillary Acidic Protein; Guinea Pigs; Hydrocortisone; Male; Microtubule-Associated Proteins; Myelin Basic Protein; Myelin Sheath; Neuroglia; Neurons; Pregnancy; Pregnanolone; Premature Birth; Progesterone; Steroids

The objective of this study was to determine whether the presence of maternal tooth periapical lesions was associated with foetal brain inflammation in a pregnant rat model.. Sprague-Dawley rats were divided into two groups: pregnant rats with induced periapical abscesses (E, n=8) and sham-operated control pregnant rats (S, n=8). The pulps of the first and second maxillary right molars had been exposed and the tooth left open to the oral environment for two weeks prior to initiation of the pregnancy. Following delivery of the pups (E, n=99; S, n=101), each pup was decapitated and the brain was removed and immediately frozen in liquid nitrogen. The tissues were solubilized in PBS containing a protease inhibitor, and norepinephrine (NE), IL-6, IL-1-β, TNF-α, and myelin basic protein (MBP) were determined by ELISA. Group means were compared by factorial analysis of variance, a post hoc Tukey test, and Pearson's correlation test. p<0.05 was used to reject the null hypothesis.. E pups were significantly heavier than S pups. Brain tissue concentrations of IL-6, IL-1-β, and TNF-α were significantly higher and MBP and norepinephrine concentrations significantly lower in E pups than S pups. Concentrations of IL-6, TNF-α and IL-1-β were significantly correlated between E serum, pup birthweight, and E pup brain tissue. MBP, NE and IL-6 were significantly correlated within the brain tissues of E pups.. The data suggest that brain inflammation may be associated with maternal periapical inflammation. This association identifies a modifiable risk factor for adverse pregnancy outcomes.

Topics: Animals; Biomarkers; Birth Weight; Blood Glucose; Brain; Brain Chemistry; Encephalitis; Female; Interleukin-1beta; Interleukin-6; Myelin Basic Protein; Norepinephrine; Periapical Abscess; Pregnancy; Pregnancy Complications, Infectious; Rats; Rats, Sprague-Dawley; Spectrophotometry; Tumor Necrosis Factor-alpha

We compared myelination of the cerebellum, brain stem, and spinal cord in the largest and smallest pig fetuses within a litter during late gestation. Gilts were killed on Days 92, 100, and 110 of gestation and these neural tissues were obtained from the largest and smallest fetuses in each litter. Myelin basic protein (MBP) mRNA was quantified in each tissue using real time reverse transcriptase polymerase chain reaction (rtPCR). Myelin was recovered from each tissue and sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and thin layer chromatography (TLC) was used to measure MBP and lipids, respectively. MBP mRNA increased with advancing gestation in all three tissues examined (P≤0.05) and was less in brain stem of small piglets compared to large piglets (P<0.01). Two coomassie stained protein bands (HMBP and LMBP) were observed by SDS-PAGE. Six prominent lipid bands were obtained by TLC (cholesterol, hydroxy(h)-cerebroside, nonhydroxy(nh)-cerebroside, phosphatidylethanolamine, phosphatidylcholine, and sphingomyelin). Significant day by fetal size interactions for cerebellar MBP and lipids indicated that cerebellar myelination in the smallest fetuses was less compared to the largest fetuses on Days 100 and 110 of gestation. Myelin MBP and lipid obtained from brain stem increased with advancing gestation and LMBP and lipids were less in small piglets compared to large piglets. In contrast, myelination in spinal cord increased with day of gestation but was not different between smallest and largest fetuses. These results confirm that myelination of the cerebellum and brain stem, but not spinal cord, is reduced in small fetuses during late gestation.

Topics: Animals; Birth Weight; Brain Stem; Cerebellum; Chromatography, Thin Layer; Electrophoresis, Polyacrylamide Gel; Female; Fetus; Lipid Metabolism; Litter Size; Myelin Basic Protein; Myelin Sheath; Pregnancy; Real-Time Polymerase Chain Reaction; RNA; Spinal Cord; Swine

The immune system plays an important role in the control of cancer development. To investigate possible genetic contribution to childhood leukemia risk in the innate immune system, we performed an association study for the 1214 SNPs in 146 gene regions related to innate immunity using GoldenGate (Illumina) oligonucleotide pool assay (OPA) in 106 case patients and 123 controls. Childhood leukemia risk was estimated as odds ratios and 95% confidence intervals adjusted for age, gender and birth weight. The minP test was used to identify statistically significant association at gene level. Three SNPs (STAT6 rs703817, C1qG rs17433222, and MBP rs3794845) were significantly associated with childhood leukemia risk (p(trend) < 0.001, minP < 0.01). The most significant association with childhood leukemia risk was for STAT6 rs703817 (GA vs GG: 0.48 (0.26-0.87), AA vs GG: 0.21 (0.07-0.61), p(trend) = 0.0003, minP = 0.002). Subgroup analysis showed that Ly96 rs78380171 and MBP rs3794845 were significantly associated with the risk of acute lymphoblastic leukemia (p(trend) < 0.001). Our results suggest that genetic polymorphisms in innate immunity genes might play a role in the genesis of childhood leukemia with limited biologic evidence. Additional, larger studies are needed to identify the mechanism of these genes in childhood leukemia patients.

Topics: Adolescent; Asian People; Birth Weight; Child; Child, Preschool; Complement C1q; Female; Gene Frequency; Genotype; Heterozygote; Homozygote; Humans; Immunity, Innate; Korea; Leukemia; Leukemia, Myeloid, Acute; Lymphocyte Antigen 96; Male; Myelin Basic Protein; Polymorphism, Single Nucleotide; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Risk; STAT6 Transcription Factor