“
“The subfornical organ is an essential central nucleus for angiotensin II-induced body fluid regulation. Similar to angiotensin II, centrally injected neurokinin B (NKB) may induce cardiovascular responses by the subfornical organ; however, it does not induce water intake. To clarify this inconsistency, we investigated the neuronal effects of NKB on subfornical organ neurons in slice preparations along with its behavioral effects in vivo.

In electrophysiological extracellular recordings, NKB excited angiotensin II-insensitive and inhibited angiotensin II-sensitive neurons. Centrally injected NKB inhibited peripherally injected angiotensin II-induced water intake. These results suggest that NKB-mediated neuronal effects on the subfornical organ are likely to be involved in antidipsogenic responses in addition to the previously reported CH5183284 clinical trial cardiovascular responses. NeuroReport 22:374-378 (C) 2011 Wolters Kluwer Health

| Lippincott Williams & Wilkins.”
“Learning and memory processes critically involve the orchestrated regulation of de novo protein synthesis. On the other hand it has become clear that regulated protein degradation also plays a major role in neuronal plasticity and learning behavior. One of the key pathways mediating protein degradation is proteosomal protein destruction. The anaphase-promoting complex/cyclosome (APC/C) is an E3 ubiquitin ligase that targets proteins for proteosomal degradation by the 26S proteasome. CP-690550 in vitro While the APC/C is essential for cell cycle progression Tryptophan synthase it is also expressed in postmitotic neurons where it has been implicated with axonal outgrowth and neuronal survival. In this study we addressed the role of APC/C in learning and memory function by generating mice that lack the essential subunit APC2 from excitatory neurons of the adult forebrain. Those animals are viable but exhibit

a severe impairment in the ability to extinct fear memories, a process critical for the treatment of anxiety diseases such as phobia or post-traumatic stress disorder. Since deregulated protein degradation and APC/C activity has been implicated with neurodegeneration we also analyzed the effect of Apc2 deletion in a mouse model for Alzheimer’s disease. In our experimental setting loss of APC2 form principle forebrain neurons did not affect the course of pathology in an Alzheimer’s disease mouse model. In conclusion, our data provides genetic evidence that APC/C activity in the adult forebrain is required for cognitive function.”
“One of the major limitations in studying the mechanisms of blast-induced traumatic brain injury (bTBI) or screening therapeutics for protection is the lack of suitable laboratory model systems that can closely mimic the complex blast exposure.