Loss of intercalated cells (ITCs) in the mouse amygdala of Tshz1 mutants correlates with fear, depression and social interaction phenotypes.

Contains fulltext : 181454.pdf (publisher's version ) (Open Access)71 p

Strain Differences in Response to Traumatic Brain Injury in Long-Evans Compared to Sprague-Dawley Rats

The selected strain of rodent used in experimental models of traumatic brain injury is typically dependent upon the experimental questions asked and the familiarity of the investigator with a specific rodent strain. This archival study compares the injury responsiveness and recovery profiles of two popular outbred strains, the Long-Evans (LE) and the Sprague-Dawley (SD), after brain injury induced by lateral fluid percussion injury (LFPI). General findings include a significantly longer duration of unconsciousness in LE rats, but similar durations of apnea. Both strains displayed the same level of initial FPI-induced behavioral deficits, followed by a more rapid rate of functional recovery in SD rats. Cortical volume loss was not significantly different, but close inspection of the data suggests the possibility that LE rats may be more susceptible to damage in the hemisphere contralateral to the injury site than are SD rats. It is hoped that the information provided here encourages greater attention to the subtle differences and similarities between strains in future pre-clinical efficacy studies of traumatic brain injury

Modulation of Polycystic Kidney Disease Severity by Phosphodiesterase 1 and 3 Subfamilies

Item does not contain fulltextAberrant intracellular calcium levels and increased cAMP signaling contribute to the development of polycystic kidney disease (PKD). cAMP can be hydrolyzed by various phosphodiesterases (PDEs). To examine the role of cAMP hydrolysis and the most relevant PDEs in the pathogenesis of PKD, we examined cyst development in Pde1- or Pde3-knockout mice on the Pkd2(-/WS25) background (WS25 is an unstable Pkd2 allele). These PDEs were selected because of their importance in cross-talk between calcium and cyclic nucleotide signaling (PDE1), control of cell proliferation and cystic fibrosis transmembrane conductance regulator (CFTR) -driven fluid secretion (PDE3), and response to vasopressin V2 receptor activation (both). In Pkd2(-/WS25) mice, knockout of Pde1a, Pde1c, or Pde3a but not of Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein kinase A-phosphorylated (Ser133) cAMP-responsive binding protein (P-CREB), activating transcription factor-1, and CREB-induced CRE modulator proteins in kidney nuclear preparations. Immunostaining also revealed higher expression of P-CREB in Pkd2(-/) (WS25);Pde1a(-/-), Pkd2(-) (/WS25);Pde1c(-/-), and Pkd2(-/) (WS25);Pde3a(-/-) kidneys. The cystogenic effect of desmopressin administration was markedly enhanced in Pkd2(-/WS25);Pde3a(-/-) mice, despite PDE3 accounting for only a small fraction of renal cAMP PDE activity. These observations show that calcium- and calmodulin-dependent PDEs (PDE1A and PDE1C) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalized cAMP pools that control cell proliferation and CFTR-driven fluid secretion. Treatments capable of increasing the expression or activity of these PDEs may, therefore, retard the development of PKD