Involvement of dopamine, but not norepinephrine, in the sex-specific regulation of juvenile socially rewarding behavior by vasopressin.

Social play is a highly rewarding behavior displayed mostly during the juvenile period. We recently showed that vasopressin V1a receptor (V1aR) blockade in the lateral septum (LS) enhances social play in male juvenile rats, but reduces it in females. Here, we determined whether the LS-AVP system modulates dopamine (DA) and/or norepinephrine (NE) neurotransmission in the LS to regulate social play behavior in sex-specific ways. Using microdialysis combined with retrodialysis, we demonstrated that both LS-AVP administration and social play exposure increased extracellular LS-DA release in females, but not in males. Pharmacological blockade of LS-DA receptors reduced social play in both sexes, but required a higher dose in females. This suggests that baseline LS-DA release is sufficient for social play in males, while increased LS-DA release is necessary for social play in females. Administration of a V1aR antagonist into the LS inhibited the social play-induced increase in extracellular LS-DA release in females. Furthermore, co-administration of the DA agonist apomorphine prevented the LS-V1aR blockade-induced decrease in social play in females. This suggests that LS-V1aR blockade reduces social play in females by dampening the rise in LS-DA release. Extracellular LS-NE release was enhanced in response to pharmacological manipulations of the LS-AVP system and to social play in males and/or females, but pharmacological blockade or stimulation of LS-NE receptors did not alter social play in either sex. Overall, we define a mechanism by which the LS-AVP system alters LS-DA neurotransmission differently in males than females resulting in the sex-specific regulation of juvenile social play behavior.

Isomer-specific chromatographic profiling yields highly sensitive and specific potential N-glycan biomarkers for epithelial ovarian cancer.

Aberrant glycosylation has been observed for decades in essentially all types of cancer, and is now well established as an indicator of carcinogenesis. Mining the glycome for biomarkers, however, requires analytical methods that can rapidly separate, identify, and quantify isomeric glycans. We have developed a rapid-throughput method for chromatographic glycan profiling using microfluidic chip-based nanoflow liquid chromatography (nano-LC)/mass spectrometry. To demonstrate the utility of this method, we analyzed and compared serum samples from epithelial ovarian cancer cases (n=46) and healthy control individuals (n=48). Over 250 N-linked glycan compound peaks with over 100 distinct N-linked glycan compositions were identified. Statistical testing identified 26 potential glycan biomarkers based on both compositional and structure-specific analyses. Using these results, an optimized model was created incorporating the combined abundances of seven potential glycan biomarkers. The receiver operating characteristic (ROC) curve of this optimized model had an area under the curve (AUC) of 0.96, indicating robust discrimination between cancer cases and healthy controls. Rapid-throughput chromatographic glycan profiling was found to be an effective platform for structure-specific biomarker discovery.

Comprehensive native glycan profiling with isomer separation and quantitation for the discovery of cancer biomarkers.

Glycosylation is highly sensitive to the biochemical environment and has been implicated in many diseases including cancer. Glycan compositional profiling of human serum with mass spectrometry has already identified potential biomarkers for several types of cancer and diseases; however, composition alone does not fully describe glycan stereo- and regioisomeric diversity. The vast structural heterogeneity of glycans presents a formidable analytical challenge. We have developed a method to identify and quantify isomeric native glycans using nanoflow liquid chromatography (nano-LC)/mass spectrometry. A microfluidic chip packed with graphitized carbon was used to chromatographically separate the glycans. To determine the utility of this method for structure-specific biomarker discovery, we analyzed serum samples from two groups of prostate cancer patients with different prognoses. More than 300 N-glycan species (including isomeric structures) were identified, corresponding to over 100 N-glycan compositions. Statistical tests established significant differences in glycan abundances between patient groups. This method provides comprehensive, selective, and quantitative glycan profiling.