It remains poorly understood as to how newly synthesized proteins that are required to act at specific synapses are translocated into only selected subsets of potentiated dendritic spines. Here, we report that F-actin, a major component of the skeletal structure of dendritic spines, may contribute to the regulation of synaptic specificity of protein translocation. We found that the stabilization of F-actin blocked the translocation of GFP-CaMKII and inhibited the diffusion of 3-kDa dextran into spines (in 2-3 weeks cultures). Neuronal activation in hippocampal slices and cultured neurons led to an increase in the activation (decrease in the phosphorylation) of the actin depolymerization factor, cofilin, and a decrease in F-actin. Furthermore, the induction of long-term potentiation by tetanic stimulation induced local transient depolymerization of F-actin both in vivo and in hippocampal slices (8-10 weeks), and this local F-actin depolymerization was blocked by APV, a N-methyl-D-aspartate (NMDA) receptor antagonist. These results suggest that F-actin may play a role in synaptic specificity by allowing protein translocation into only potentiated spines, gated through its depolymerization, which is probably triggered by the activation of NMDA receptors.

We report here that exposure to low concentrations of proteasome inhibitors (e.g. 10-100 nM MG-132, 0.1-3 nM epoxomicin or 10-30 nM clasto-lactacystin b-lactone) resulted in an enhancement, rather than an inhibition, of proteasome activity in cultured neocortical neurons. Size-fractionation chromatography confirmed that the enhanced peptide cleavage activity was associated with proteasome-sized complexes. This sub toxic exposure reduced neuronal death caused by subsequent exposure to oxidative stress (100-200 lM H 2 O 2 for 30 min, 24-h exposure to 100 lM paraquat or 7.5 lM menadione), but did not alter vulnerability to excitotoxicity (5-min exposure to 30-100 lM NMDA or 24 exposure to 12 lM NMDA). Sub toxic proteasome inhibitor exposure caused an increase in levels of proteasome core subunit proteins and mRNAs, but not in levels of potentially cytoprotective heat shock proteins (hsp70, hsp90 and hsp40). The neuroprotective effects of proteasome inhibitor pre-treatment were blocked by coapplication of proteasome inhibitors during the oxidative insult. These findings support a model in which sublethal proteasome inhibition induces neurons to increase proteasome activity and promotes resistance to oxidative injury and suggests that enhancement of proteasome activity is a potential therapeutic target for diseases in which oxidative stress has been implicated.

No abstract

The current study aimed to investigate the anti-osteoporotic effects of a Lactobacillus plantarum B719-fermented milk product (FMP-B719). Higher proliferation and mineralisation were observed in FMP-B719-treated MC3T3-E1 mouse pre-osteoblastic cells than those in L. casei ATCC 393-FMP-treated MC3T3-E1 cells. Moreover, FMP-B719 normalised the serum alkaline phosphatase (9.37 AE 1.92 U/L) and phosphorus (8.28 AE 0.1 mg/dL) in a rat model of ovariectomy-induced postmenopausal osteoporosis. Furthermore, FMP-B719 normalized the bone volume in the proximal femur and increased the femur strength that was decreased in ovariectomized rats. Hence, the results of this study suggest that FMP-B719 could serve as a potential candidate for the treatment and prevention of postmenopausal osteoporosis.

Galectin-1 is a member of beta-galactoside-binding lectins expressed in a variety of mammalian tissues. We report here that galectin-1 mRNA is abundantly expressed in the mouse reproductive organs such as the uterus and ovary. Uterine expression of galectin-1 mRNA is specifically regulated in the embryonic implantation process. Its expression increased at a high level on the fifth day post coitum (dpc 5) when embryos hatched into the endometrial epithelial cells. In the absence of embryos, however, galectin-1 expression in the mouse uterus decreased on dpc 5. In the delayed implantation mice, galectin-1 mRNA levels was augmented by the termination of the delay of implantation. Ovarian steroids progesterone and estrogen differentially regulated galectin-1 mRNA level in uterine tissues. Treatment with RU486, a progesterone receptor antagonist, blocked progesterone-induced galectin-1 mRNA level in uterine tissues of ovariectomized mouse. ICI182780, a pure estrogen receptor antagonist, clearly blocked the estrogen effect. Taken together, galectin-1 gene expression in the uterine tissues was regulated by ovarian steroids and this regulation correlated with the implantation process.

No abstract

Aim In this study, we investigated the anti‐osteoporotic effect of two fermented milk products (FMPs) fermented by Lactobacillus plantarum A41 and Lactobacillus fermentum SRK414 on a rat model of ovariectomy‐induced post‐menopausal primary osteoporosis. Methods and Results The two Lactobacillus FMPs increased the bone volume and bone mineral density (BMD) in ovariectomized (OVX) rats, and normalized the bone biomarkers in the serum. Additionally, they altered the gene expression levels of bone‐metabolism‐related markers. Furthermore, the two Lactobacillus FMPs downregulated bone‐apoptosis‐related genes stimulated by ovariectomy. Interestingly, the Lactobacillus FMPs decreased the levels of inflammation markers in the serum, bone, ileum and colon of the rats. Gut bacterial populations were also affected upon FMP treatment due to increase in the abundance of the genus Lactobacillus and Faecalibacterium prausnitzii. Conclusions Milk products fermented by L. plantarum A41 and L. fermentum SRK414 can exhibit anti‐osteoporotic effects on post‐menopausal osteoporosis via regulating the expression of bone‐metabolism‐related markers. Significance and Impact of the Study The two Lactobacillus FMPs used in the study can be an ideal method that has its potential of treating post‐menopausal osteoporosis instead of drug treatments.

Galectin‐1 is a member of β‐galactoside‐binding lectins expressed in a variety of mammalian tissues. We report here that galectin‐1 mRNA is abundantly expressed in the mouse reproductive organs such as the uterus and ovary. Uterine expression of galectin‐1 mRNA is specifically regulated in the embryonic implantation process. Its expression increased at a high level on the fifth day post coitum (dpc 5) when embryos hatched into the endometrial epithelial cells. In the absence of embryos, however, galectin‐1 expression in the mouse uterus decreased on dpc 5. In the delayed implantation mice, galectin‐1 mRNA level was augmented by the termination of the delay of implantation. Ovarian steroids progesterone and estrogen differentially regulated galectin‐1 mRNA level in uterine tissues. Treatment with RU486, a progesterone receptor antagonist, blocked progesterone‐induced galectin‐1 mRNA level in uterine tissues of ovariectomized mouse. ICI182780, a pure estrogen receptor antagonist, clearly blocked the estrogen effect. Taken together, galectin‐1 gene expression in the uterine tissues was regulated by ovarian steroids and this regulation correlated with the implantation process. Mol. Reprod. Dev. 48:261–266, 1997. © 1997 Wiley‐Liss, Inc.