Somatostatin Receptor 1/5 Knockout and R6/2 Mice Figure 5. Western blot analysis demonstrating the changes in expression of calcineurin (61kDa), calpain (90 kDa), synapsin-IIa (74 kDa) and enkephalin (55 kDa) in tissue lysate prepared from striatum R6/2 and SSTR1/52/2 mice. Note the loss of calcineurin in SSTR1/52/2 and R6/2 mice brain striatum (a) and increased expression of calpain and synapsin-IIa (b,c). In contrast enkephalin was not changed in R6/2 mice whereas increased in SSTR1/52/2 mice brain (d). Data presented as mean 6 SD (SSTR1/52/2, n = 5 and R6/2 mice, n = 3) in comparison to wt mice brain. *P,0.05, ** P,0.01. e) Photomicrographs showing apoptosis in R6/2 and SSTR1/52/2 mice striatum. R6/2 transgenic mice displayed significantly increased number of apoptotic neuronal cells in striatum when compared to wt (e panel left). Unlike R6/2 mice, only few apoptotic neuronal cells were observed in SSTR1/52/2 mice (e panel right). Arrows represent surviving cells and arrowheads represent apoptotic cells. Scale bar = 20 mm. doi:10.1371/journal.pone.0024467.g005 apoptosis [33]. Whether increased expression of SSTR3 as seen in R6/2 mice is associated with apoptosis in HD needs further investigation. However, decreased SSTR3 expression in SSTR1/ 52/2 mice may account, albeit to a lesser degree, for apoptotic cell death in comparison to R6/2. SST via activation of SSTR subtypes blocks Ca2+ influx through the interference with NMDA function. This suggests that mice lacking SSTR1/5 may cause pronounced NMDA-induced toxicity due to the activation of NMDA receptors in SSTR1/52/2 mice. This speculation is consistent with previous studies from HD transgenic mice [18]. Furthermore, the inhibitory effect of SST on excitatory synaptic transmission is also well established in rodent brain [33]. Previous studies have shown that presymptomatic HD mice (6– 8 weeks old R6/2 mice) not only display physiological character- istics but also behavioral and neurochemcial changes similar to those observed in HD [70]. These observations indicate that SSTR1/52/2 might serve as a model to elucidate the role of SSTR subtypes to characterize the neurochemcial changes in different proteins and pathways involved in HD. SSTR5 blocks the L-type Ca2+ channels and may correlate with the increased expression of SSTR5 in R6/2 mice [71]. As SSTR5 is not predominantly expressed in mouse striatum and SSTR1 and SSTR5 are known to form heterodimers, we speculate that the increased expression of SSTR1 in R6/2 mice may be due to a PLoS ONE | www.plosone.org 9 September 2011 | Volume 6 | Issue 9 | e24467