Tachykinins Processing is Significantly Impaired in PC1 and PC2 Mutant Mouse Spinal Cord S9 Fractions

Substance P (SP) play a central role in nociceptive transmission and it is an agonist of the Neurokinin-1 receptor located in the lamina I of the spinal cord. SP is a major proteolytic product of the protachykinin-1 primarily synthesized in neurons. Proprotein convertases (PCs) are extensively expressed in the central nervous system (CNS) and specifically cleave at C-terminal of either a pair of basic amino acids, or a single basic residue. The proteolysis control of endogenous protachykinins has a profound impact on pain perception and the role of PCs remain unclear. The objective of this study was to decipher the role of PC1 and PC2 in the proteolysis surrogate protachykinins (i.e. Tachykinin 20-68 and Tachykinin 58-78) using cellular fractions of spinal cords from wild type (WT), PC1-/+ and PC2-/+ animals and mass spectrometry. Full-length Tachykinin 20-68 and Tachykinin 58-78 was incubated for 30 minutes in WT, PC1-/+ and PC2-/+ mouse spinal cord S9 fractions and specific C-terminal peptide fragments were identified and quantified by mass spectrometry. The results clearly demonstrate that both PC1 and PC2 mediate the formation of SP and Tachykinin 58-71, an important SP precursor, with over 50% reduction of the rate of formation in mutant PC 1 and PC2 mouse S9 spinal cord fractions. The results obtained revealed that PC1 and PC2 are involved in the C-terminal processing of protachykinin peptides and suggest a major role in the maturation of the protachykinin-1 protein.

Are stress and mixed urinary incontinence associated with impaired executive control in community-dwelling older women?

Objectives: To assess whether stress or mixed urinary incontinence (UI) is associated with deficits in executive functioning among community-dwelling women. Design: An observational study comparing the performance, using multivariate analyses of variance (MANOVAs) and Bonferroni post hoc test, of continent women and women with stress or mixed UI during executive control tasks. Setting: The research center of the Institut universitaire de gériatrie de Montréal. Participants: One hundred and fifty-five community-dwelling women aged 60 and older participated in the study. Measurements: Based on the Urogenital Distress Inventory (UDI), participants were split into three groups: 35 continent women, 43 women with stress UI, and 78 women with mixed UI. Participants completed a battery of neuropsychological tests and a computerized dual-task test. Results: Women with mixed UI showed poorer performances than continent and stress UI women in executive control functions. Deficits were specific to tests involving switching and sharing/dividing attention between two tasks. Conclusion: Results of this study suggest that mixed UI can be associated with executive control deficits in community-dwelling older women. Future intervention studies in the treatment of UI should take the higher risk of an executive control deficit in women with UI under consideration.