Depression-like behaviors induced by defective PTPRT activity through dysregulated synaptic functions and neurogenesis.

PTPRT has been known to regulate synaptic formation and dendritic arborization of hippocampal neurons. PTPRT-/- null and PTPRT-D401A mutant mice displayed enhanced depression-like behaviors compared with wild-type mice. Transient knockdown of PTPRT in the dentate gyrus enhanced the depression-like behaviors of wild-type mice, whereas rescued expression of PTPRT ameliorated the behaviors of PTPRT-null mice. Chronic stress exposure reduced expression of PTPRT in the hippocampus of mice. In PTPRT-deficient mice the expression of GluR2 (also known as GRIA2) was attenuated as a consequence of dysregulated tyrosine phosphorylation, and the long-term potentiation at perforant-dentate gyrus synapses was augmented. The inhibitory synaptic transmission of the dentate gyrus and hippocampal GABA concentration were reduced in PTPRT-deficient mice. In addition, the hippocampal expression of GABA transporter GAT3 (also known as SLC6A11) was decreased, and its tyrosine phosphorylation was increased in PTPRT-deficient mice. PTPRT-deficient mice displayed reduced numbers and neurite length of newborn granule cells in the dentate gyrus and had attenuated neurogenic ability of embryonic hippocampal neural stem cells. In conclusion, our findings show that the physiological roles of PTPRT in hippocampal neurogenesis, as well as synaptic functions, are involved in the pathogenesis of depressive disorder.

Mesenchymal Stem Cells Ameliorate Renal Inflammation in Adriamycin-induced Nephropathy.

Mesenchymal stem cells (MSCs) ameliorate the renal injury in Adriamycin (ADR)-induced nephropathy, but the mechanisms underlying their efficacy remain incompletely understood. In this study, we demonstrated that MSCs increased the survival, recovered body weight loss, and decreased proteinuria and serum creatinine levels in ADR-treated mice. MSCs also prevented podocyte damage and renal fibrosis by decreasing the expression of fibronectin, collagen 1α1, and α-smooth muscle actin. From a mechanistic perspective, MSCs inhibited renal inflammation by lowering the expression of CCL4, CCL7, CCL19, IFN-α/ß, TGF-ß, TNF-α, and chitinase 3-like 1. In summary, our data demonstrate that MSCs improve renal functions by inhibiting renal inflammation in ADR-induced nephropathy.

Phenylpropanoids from cinnamon bark reduced ß-amyloid production by the inhibition of ß-secretase in Chinese hamster ovarian cells stably expressing amyloid precursor protein.

ß-Amyloid (Aß) is a substance of Alzheimer disease (AD), which is generated via the amyloidogenic pathway from amyloid precursor protein (APP) by ß-secretase and γ-secretase. Inhibition of Aß production is a potential therapeutic approach to AD. Thus, we tested the hypothesis that cinnamon bark (Cinnamomi Cortex Spissus), the dried bark of Cinnamomum cassia Blume (Lauraceae), and its constituents are beneficial to AD. The methanol extract of cinnamon bark efficiently reduced Aß40 production in Chinese hamster ovarian (CHO) cells stably expressing APP as determined by enzyme-linked immunosorbent assay. Bioassay-guided isolation of cinnamon bark extract was carried out using open column chromatography and high-performance liquid chromatography, and the following 6 phenylpropanoids were isolated: syringaresinol (1); medioresinol (2); coumarin (3); 2-hydroxycinnamaldehyde (4); cryptamygin A (5); and 3',5,7-trimethoxy epicatechin (6). Among these, 4 µg/mL medioresinol and cryptamygin A reduced Aß40 production by 50% and 60%, respectively, compared with dimethyl sulfoxide-treated control cells. The IC50 values of medioresinol and cryptamygin A for the inhibition of Aß40 production were 10.8 and 8.2 µg/mL, respectively. Furthermore, treatment of APP-CHO cells with either compound decreased the amount of ß-secretase and sAPPß (the proteolytic fragment of APP catalyzed by ß-secretase). These results suggest that the antiamyloidogenic activity of cinnamon bark extract was exerted by medioresinol and cryptamygin A via a reduction in the amount of ß-secretase. The extract of cinnamon bark contains potentially valuable antiamyloidogenic agents for the prevention and treatment of AD.

Usefulness of the tendon reflex for assessing spasticity after botulinum toxin-a injection in children with cerebral palsy.

This study sought to investigate the relationships between clinical and neurophysiologic assessments of spasticity after injection of botulinum toxin-A in children with cerebral palsy. A total of 40 children were recruited. Clinical assessments included the modified Ashworth scale and modified Tardieu scale parameters R1, R2, and D. Neurophysiologic assessment included compound motor action potential, Hoffmann, and tendon reflex. Children showed significant decreases in modified Ashworth scale, R1, and R2 at 2, 4, and 12 weeks and in D at 2 and 4 weeks. Amplitude of compound motor action potential decreased at 2 weeks, Hoffmann reflex amplitude decreased at 4 weeks, and tendon reflex amplitude decreased at 2 and 4 weeks. At 12 weeks, none of the neurophysiologic parameters differed from baseline. The correlations among R2, D, and the amplitude of tendon reflex were significant. Neurophysiologic tests could be used to evaluate reduced spasticity after botulinum toxin-A injection. The amplitude of tendon reflex showed the highest correlation with severity of spasticity.