Daleymcmahon3016
Trans-synaptic cell-adhesion molecules are critical for governing various stages of synapse development and specifying neural circuit properties via the formation of multifarious signaling pathways. Recent studies have pinpointed the putative roles of trans-synaptic cell-adhesion molecules in mediating various cognitive functions. Here, we review the literature on the roles of a diverse group of central synaptic organizers, including neurexins (Nrxns), leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs), and their associated binding proteins, in regulating properties of specific type of synapses and neural circuits. In addition, we highlight the findings that aberrant synaptic adhesion signaling leads to alterations in the structures, transmission, and plasticity of specific synapses across diverse brain areas. These results seem to suggest that proper trans-synaptic signaling pathways by Nrxns, LAR-RPTPs, and their interacting network is likely to constitute central molecular complexes that form the basis for cognitive functions, and that these complexes are heterogeneously and complexly disrupted in many neuropsychiatric and neurodevelopmental disorders.
Cognitive impairment is a common complication in chronic kidney disease (CKD) patients. Currently, limited types of animal models are available for studying cognitive impairment in CKD. We used unilateral ureteral obstruction (UUO) in mice as an animal model to study the cognitive changes and related pathology under prolonged renal impairment METHODS UUO was performed in 8-week-old male C57BL/6 N mice with double-ligation of their left ureter. A sham group was subjected to the same experimental procedure without ureteral obstruction. Cognitive and behavioral tests were performed to examine potential changes in cognition and behavior at 2, 4 and 12 weeks after surgery. Sera were collected, and kidneys and brains were harvested for the detection of systemic inflammation markers and neurodegenerative changes.
These mice displayed weak performance in the novel object recognition test, Y-maze test, and puzzle box test compared to the sham group. Reductions in synaptic proteins such as synapsin-1, synaptophysin, synaptotagmin, PSD95, NMDAR2B and AMPAR were confirmed by western blot analysis. Histological examination revealed elevated levels of Nrf2 and 8-hydroxyguanosine, and hyperphosphorylation of tau in the hippocampus. UUO mice also had increased levels of C-reactive protein (CRP) and TNF-α.
We characterized the cognitive and neuropathological changes in UUO mice. The results show that this mouse model can be used to further study cognitive changes related to chronic renal impairment.
We characterized the cognitive and neuropathological changes in UUO mice. The results show that this mouse model can be used to further study cognitive changes related to chronic renal impairment.Carbon monoxide (CO) and nitric oxide (NO) modulate inflammatory nociception and anxiety. We evaluate whether treatments with a heme oxygenase-1 (HO-1) inducer (CoPP) or a carbon monoxide-releasing molecule (CORM-2) are capable of inhibiting inflammatory pain aversiveness in wild type (WT) and inducible nitric oxide synthase-knock out (NOS2-KO) mice with persistent inflammation and its relationship with μ- (MOR) and δ- (DOR) opioid receptors. WT and NOS2-KO male mice with complete Freund's adjuvant (CFA) injected into the hind paw were evaluated in the von Frey and the escape-avoidance paradigm (PEAP) tests, at 10 days, before and after the treatment with CORM-2 (5 mg/kg) or CoPP (2.5 mg/kg). WT mice groups treated with CORM-2 or CoPP also received naloxone (NLX, a non-specific opioid receptor antagonist). The HO-1, neuronal nitric oxide synthase, NOS2, MOR, and DOR expression in the dorsal hippocampus were evaluated by western blot. CFA reduced mechanical threshold in WT and NOS2-KO mice but only increased the percentage of time in the light compartment in the PEAP in WT mice. CORM-2 and CoPP inhibited these effects in both strains. Pre-treatment with NLX reverses the anti-allodynic and anti-aversive effects of CORM-2 or CoPP in WT mice. CORM-2 and CoPP increases the protein levels of HO-1, MOR and DOR in the dorsal hippocampus of WT mice but not in NOS2-KO animals. Streptozocin Results showed that HOCO pathway activation promotes anti-allodynic effects and reduced pain aversiveness caused by peripheral inflammation by increasing the expression of MOR and DOR activated by HO-1 in the dorsal hippocampus.
Cervical pessary has been proven to be effective in reducing the rate of preterm birth in asymptomatic women with singleton gestations and short cervical length in the midtrimester of pregnancy; however, the efficacy of this device in women with arrested preterm labor is still a subject of debate.
This study aimed to test the hypothesis that the use of a cervical pessary in women with singleton pregnancy and arrested preterm labor would reduce the risk of preterm birth at <37 weeks of gestation.
This study is a parallel group, nonblinded, randomized trial. Participants included in the study were women with a diagnosis of arrested preterm labor between 24 0/7 and 33 6/7 weeks of gestations. The participants were randomized to either the cervical pessary group or no pessary group in a 11 ratio. The primary endpoint was preterm birth at <37 weeks of gestation. A sample size of 120 participants was determined, but the trial was concluded before the completion of enrollment.
A total of 61 women with singleton pregnancies and arrested preterm labor at 24 0/7 to 33 6/7 weeks of gestation were enrolled in the trial. Of the 61 women, 32 were randomized to the cervical pessary group and 29 to the control group. Preterm birth at <37 weeks of gestation occurred in 14 women (43.8%) in the pessary group and 6 women (20.7%) in the control group (relative risk, 2.98; 95% confidence interval, 0.96-9.30).
In this underpowered trial, among women with singleton pregnancies and arrested preterm labor, compared with no pessary use, the use of a cervical pessary does not result in a lower rate of preterm birth at <37 weeks of gestation.
In this underpowered trial, among women with singleton pregnancies and arrested preterm labor, compared with no pessary use, the use of a cervical pessary does not result in a lower rate of preterm birth at less then 37 weeks of gestation.