Effects of dietary active soybean trypsin inhibitors on pancreatic weights, histology and expression of STAT3 and receptors for androgen and estrogen in different tissues of rats.

Our previous study showed that soy milks could contain high levels of active soybean trypsin inhibitors (SBTI) if they were not properly processed. This study investigated the effects of consuming active SBTI on pancreatic weights, histology, trypsinogen production and expression of STAT3, receptors for androgen (AR) and estrogen (ER) in pancreas, liver and uterus of rats. Weanling Sprague-Dawley rats were randomly divided into 3 groups (8 females and 8 males/group) and fed diets containing either 20% casein protein (Casein) or 20% soy protein (SP) in the presence of high (1.42 BAEE unit/µg, SP + SBTI) or low (0.2 BAEE unit/µg, SP-SBTI) levels of active SBTI for 8 weeks. Ingestion of SP + SBTI diet markedly increased pancreatic weights and trypsinogen content (p < 0.01), and caused acinar cell hypertrophy, and reduced pancreatic STAT3, p-STAT3, AR and ERß content, and increased uterine ERα and ERß compared to the Casein or SP-SBTI diets (p < 0.05). The two SP-containing diets lowered hepatic STAT3, p-STAT3, and pancreatic ERα, and increased hepatic ERα and ERß content in the female rats compared to the Casein diet (p < 0.05). This study demonstrated for the first time that consumption of high level of active SBTI not only increased pancreatic weights and acinar cell secretions, but also attenuated the expression of pancreatic STAT3, p-STAT3, AR, and ERß proteins in both sexes and increased uterine ERα and ERß content, and that dietary soy protein affected hepatic STAT3, p-STAT3, ERα and ERß in a gender-dependent manner.

Sigma receptor type 1 knockout mice show a mild deficit in plasticity but no significant change in synaptic transmission in the CA1 region of the hippocampus.

The sigma-1 receptor (σ-1R) is a chaperone protein located at the endoplasmic reticulum (ER) mitochondrial interface with roles in neuroprotection and cognition. Increasing evidence suggests that loss of σ-1R function could contribute to neurological disease states making it a target for therapeutic intervention. Our objective was to elucidate the consequences to synaptic transmission and plasticity when σ-1R is absent. We utilized a knockout mouse in which the gene encoding for σ-1R was deleted (σ-1R-KO mouse). Using whole-cell patch-clamp recordings from CA1 pyramidal neurons in the hippocampus, we examined neuronal excitability and glutamatergic synaptic function. Surprisingly, we detected no significant change in action potential firing and basic cellular characteristics. Furthermore, we found no significant change to pre-synaptic function as indicated by a similar paired-pulse ratio and miniature excitatory post-synaptic current frequency in σ-1R-KO compared to wild-type (WT) mice. Similarly, the glutamate gated AMPA receptor and NMDA receptors were unaffected with no significant difference in AMPA/NMDA ratio or decay kinetics in σ-1R-KO compared to WT mice. We further examined long-term potentiation in extracellular field recordings in CA1 stratum radiatum following Schaffer collateral stimulation. Interestingly, we found a small but significant reduction in the magnitude of long-term potentiation in mutant compared to WT mice. The results of this investigation suggest that basic cellular physiology is unaffected by σ-1R loss, however the neuronal network is partially compromised. The sigma-1 receptor (σ-1R) is a chaperone protein with roles in neuroprotection and cognition. We determined the consequences to synaptic transmission and plasticity when σ-1R was absent. Utilizing the σ-1R knockout mouse and electrophysiological recordings, we found no change in neuronal excitability and glutamatergic synaptic function. However, we found a significant reduction in long-term potentiation.

Molecular basis for convergent evolution of glutamate recognition by pentameric ligand-gated ion channels.

Glutamate is an indispensable neurotransmitter, triggering postsynaptic signals upon recognition by postsynaptic receptors. We questioned the phylogenetic position and the molecular details of when and where glutamate recognition arose in the glutamate-gated chloride channels. Experiments revealed that glutamate recognition requires an arginine residue in the base of the binding site, which originated at least three distinct times according to phylogenetic analysis. Most remarkably, the arginine emerged on the principal face of the binding site in the Lophotrochozoan lineage, but 65 amino acids upstream, on the complementary face, in the Ecdysozoan lineage. This combined experimental and computational approach throws new light on the evolution of synaptic signalling.