Synapse formation and elimination occur throughout life, but the magnitude of such changes at distinct developmental stages remains unclear. Using transgenic mice overexpressing yellow fluorescent protein and transcranial two-photon microscopy, we repeatedly imaged dendritic spines on the apical dendrites of layer 5 pyramidal neurons. In young adolescent mice (1-month-old), 13%-20% of spines were eliminated and 5%-8% formed over 2 weeks in barrel, motor, and frontal cortices, indicating a cortical-wide spine loss during this developmental period. As animals mature, there is also a substantial loss of dendritic filopodia involved in spinogenesis. In adult mice (4-6 months old), 3%-5% of spines were eliminated and formed over 2 weeks in various cortical regions. Over 18 months, only 26% of spines were eliminated and 19% formed in adult barrel cortex. Thus, after a concurrent loss of spines and spine precursors in diverse regions of young adolescent cortex, spines become stable and a majority of them can last throughout life.

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Pituitary adenylate cyclase-activating polypeptide (PACAP), a neuropeptide that acts through G proteincoupled receptors, exerts neuroprotective effects upon many neuronal populations. However, the intracellular signaling mechanisms that account for PACAP's trophic effects are not well characterized. Here we have tested the possibility that PACAP uses neurotrophin signaling pathways. We have found that PACAP treatment resulted in an increase in TrkA tyrosine kinase activity in PC12 cells and TrkB activity in hippocampal neurons. The activation of TrkA receptors by PACAP required at least 1 h of treatment and did not involve binding to nerve growth factor. Moreover, PACAP induced an increase in activated Akt through a Trk-dependent mechanism that resulted in increased cell survival after trophic factor withdrawal. The increases in Trk and Akt were blocked by K252a, an inhibitor of Trk receptor activity. In addition, transactivation of TrkA receptors by PACAP could be inhibited with PP1, an inhibitor of Src family kinases or BAPTA/AM, (1,2-bis(2-aminophenoxy)ethane-N,N,N,N-tetraacetic acid acetoxymethyl ester), an intracellular calcium chelator. Therefore, PACAP can exert trophic effects through a mechanism involving Trk receptors and utilization of tyrosine kinase signaling. This ability may explain several neuroprotective actions of PACAP upon neuronal populations after injury, nerve lesion, or neurotrophin deprivation.Neurotrophic effects are generally associated with the action of polypeptide growth factors, such as the NGF 1 neurotrophin, ciliary neurotrophic factor (CNTF), and glial-derived neurotrophic factor families. Each represents small families of proteins that are essential for the development of the vertebrate nervous system. The effects of these factors on cell survival, differentiation, and cell death events depend upon binding to transmembrane receptors and stimulation of downstream signaling cascades characterized by increased protein tyrosine phosphorylation. Neurotrophins utilize Trk receptor tyrosine kinases, and glial-derived neurotrophic factor family members signal through the c-Ret receptor tyrosine kinase, whereas CNTF utilizes JAK tyrosine kinase activity linked to the CNTF receptor complex (1).It has become increasingly apparent that many other secreted proteins are also capable of providing neuroprotective or neurotrophic actions. The pituitary adenylate cyclase-activating polypeptide (PACAP) belongs to a family of peptides, including secretin, glucagon, and vasoactive intestinal peptide (VIP) (2, 3). PACAP exists in two active forms of 38 (PACAP38) and 27 amino acids (PACAP27). Although PACAP was originally isolated from the hypothalamus, it is distributed throughout the central nervous system, including the hippocampus, olfactory bulb, and cerebral cortex (4 -9).The biological effects of PACAP are mediated by seven-transmembrane-spanning receptors. Two G protein-coupled receptors exist for PACAP. The type 1 PACAP receptor, PAC1, displays high specificity for PACAP (10), whereas type I...

Intussusception found in the 1st month of life is rare and usually discussed as one entity, neonatal intussusception, but in fact, includes the intussusceptions occurring both prenatally and neonatally, of which the clinical presentations and results are different. Four full-term babies with prenatal intussusception presenting as intestinal atresia (IA) and three premature babies with neonatal intussusception mimicking necrotizing enterocolitis (NEC) are presented. Prenatal intussusception, as one of the causes of IA produces prominent signs of intestinal obstruction immediately after birth. Preoperative evaluation usually fails to yield a definitive diagnosis, but surgery is usually performed in time and is successful. In neonatal intussusception, full-term infants usually have a pathological lead point and the colon is almost always involved. A barium enema is thus useful in diagnosis. Premature babies, on the other hand, rarely have a colonic component, and the clinical features are insidious and similar to NEC. This results in diagnostic confusion that may lead to a dangerous delay in appropriate surgical correction. A high level of suspicion about this condition in cases diagnosed presumptively with NEC is important. Serial abdominal sonograms may be helpful in the early diagnosis of neonatal intussusception.

Risk factors for chronic kidney disease (CKD), such as hypertension, hyperglycemia, albuminuria, renal structure, and sex hormones, have been reported to have different effects on males and females. Thus, CKD progression may differ depending on sex. In addition to CKD management, treatment at earlier stages can reduce complications and prevent disease progression as well as high medical expenses at late stages. We examined the differences in predictive risk factors for renal progression between male and female patients with early CKD.This case–cohort study recruited patients aged 18 years or older treated in the outpatient departments of 8 hospitals in Taiwan between August 2008 and September 2014. In total, 1530 patients were included in the analysis. Renal progression was defined as ≥25% decline based on baseline estimated glomerular filtration rate. To examine the predictive risk factors for renal progression, we constructed a subset multivariate logistic model with stepwise variable selection by using P < 0.10 for variable retention.The numbers of male and female patients with CKD exhibiting renal progression were 100 (11.64%) and 84 (12.52%), respectively. After adjusting for all the potential confounders, stepwise logistic regression analysis showed that main independent predictive risk factors for the male patients– (C statistic = 0.72) were proteinuria (odds ratio [OR] 2.20; 95% confidence interval [CI] 1.26–3.84), age (OR 1.04; 95% CI 1.02–1.06), anemia (OR 2.75; 95% CI 1.20–6.30), and poor control of blood pressure (OR 1.84; 95% CI 1.05–3.22). However, the main independent predictive factors for the female patients were (C statistic = 0.75) poor glycemic control (OR 2.28; 95% CI 1.22–4.25), poor blood pressure control (OR 1.93; 95% CI 1.06–3.50), and family income (OR 2.51; 95% CI 1.01–6.20).In conclusion, this study demonstrated that proteinuria was the most crucial risk factor for male patients, whereas poor glycemic control was the main risk factor for female patients. Poor blood pressure control was a shared risk factor for male and female patients.

Pancreatitis can occur from a wide variety of causes and may result in severe complications. Early diagnosis, close monitoring and aggressive intervention are mandatory to reduce morbidity and mortality.

Background Anesthetics are widely used to induce unconsciousness, pain relief and immobility during surgery. It remains unclear whether the use of anesthetics has significant and long lasting effects on synapse development and plasticity in the brain. To address this question, we examined the formation and elimination of dendritic spines, postsynaptic sites of excitatory synapses, in the developing mouse cortex during and after anesthetics exposure. Methods Transgenic mice expressing yellow fluorescence protein in layer 5 pyramidal neurons were used in this study. Mice at 1 month of age underwent ketamine-xylazine and isoflurane anesthesia over a period of hours. The elimination and formation rates of dendritic spines and filopodia, the precursors of spines, were followed over hours to days in the primary somatosensory cortex using transcranial two-photon microscopy. 4–5 animals were examined under each experimental condition. Student's t-test and Mann-Whitney U-test were used to analyze the data. Results Administration of either ketamine-xylazine or isoflurane rapidly altered dendritic filopodial dynamics but had no significant effects on spine dynamics. Ketamine-xylazine increased filopodial formation while isoflurane decreased filopodial elimination during 4 hours of anesthesia. Both effects were transient and disappeared within a day after the animals woke up. Conclusion Our studies suggest that exposure to anesthetics transiently affects the dynamics of dendritic filopodia but has no significant effect on dendritic spine development and plasticity in the cortex of 1-month-old mice.

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