CaMKIIβ-mediated LIM-kinase activation plays a crucial role in BDNF-induced neuritogenesis

LIM-kinase 1 (LIMK1) regulates actin cytoskeletal reorganization by phosphorylating and inactivating actin-depolymerizing factor and cofilin. We examined the role of LIMK1 in brain-derived neurotrophic factor (BDNF)-induced neuritogenesis in primary-cultured rat cortical neurons. Knockdown of LIMK1 or expression of a kinase-dead LIMK1 mutant suppressed BDNF-induced enhancement of primary neurite formation. By contrast, expression of an active form of LIMK1 promoted primary neuritogenesis in the absence of BDNF. BDNF-induced neuritogenesis was inhibited by KN-93, an inhibitor of Ca²⁺/calmodulin-dependent protein kinases (CaMKs), but not by STO-609, an inhibitor of CaMK-kinase (CaMKK). CaMKK activity is required for the activation of CaMKI and CaMKIV, but not CaMKII, which suggests that CaMKII is principally involved in BDNF-induced enhancement of neuritogenesis. Knockdown of CaMKIIβ, but not CaMKIIα, suppressed BDNF-induced neuritogenesis. Active CaMKIIβ promoted neuritogenesis, and this promotion was inhibited by knockdown of LIMK1, indicating that CaMKIIβ is involved in BDNF-induced neuritogenesis via activation of LIMK1. Furthermore, in vitro kinase assays revealed that CaMKIIβ phosphorylates LIMK1 at Thr-508 in the kinase domain and activates the cofilin-phosphorylating activity of LIMK1. In summary, these results suggest that CaMKIIβ-mediated activation of LIMK1 plays a crucial role in BDNF-induced enhancement of primary neurite formation.     

Plasma 11-deoxycortisol response to single dose metyrapone in prostatic cancer patients (author's transl)

A radioimmunoassay procedure for plasma 11-deoxycortisol (S) was developed using an antiserum prepared by immunizing rabbits with S-21-hemisuccinate bovine serum albumin and S-3-oxime-bovine serum albumin. Thereafter plasma S, cortisol (F) and adrenocorticotropic hormone (ACTH) responses to metyrapone were investigated in 13 normal adult males and 39 patients with prostatic cancer. The results were as follows: 1) The antiserum against S-3-oxime-bovine serum albumin had less cross reactivity (less than 10%) with other steroids than that against S-21-hemisuccinate bovine serum albumin and obtained a good standard curve. The intra-assay variance and interassay variance of this method using the former antiserum (N = 10) were 12.4% asd 14.9% respectively, and the blank value was 3.7 +/- 1.6 pg. 2) Basal levels of S. F and ACTH in plasma from 13 normal adult males, ranged 21 approximately 80 years, old, were 98.4 +/- 15.7 ng/dl (mean value +/- S.E.), 12.7 +/- 0.78 micrograms/dl and 30.6 +/- 3.02 pg/ml respectively. Those level increased to 7060 +/- 598 ng/dl, 24.3 +/- 1.69 micrograms/dl and 24.3 +/- 1.6 pg/ml at 9 a.m. following oral administration of metyrapone (30 mg/kg b.w.) at midnight. 3) Both basal levels and responses of plasma S and F to metyrapone increased remarkably, while those of ACTH were within the normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and AC normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and AC normal range in prostatic cancer patients during the estrogen therapy. It was considered that protein-bound S and F increased following elevation of corticosteroid binding globulin but returned to the normal range about 2 weeks after discontinuation of the therapy. 4) In case treated wih estrogens, plasma, S, F and ACTH responses to metyrapone were unchanged compared to normal adult males 2 approximately 4 weeks after discontinuation of the therapy, and this data suggested that estrogens had no inhibitory effect on the pituitary-adrenal axis. However, in cases treated with progestational agents over a long-term period, plasma S and ACTH responses to metyrapone decreased slightly but returned to the normal range 2 approximately 4 weeks after discontinuation of the therapy. This suggested that the inhibitory effect of these agents on the pituitary-adrenal axis was mild and reversible.     

Contribution of abdominal muscle strength to various activities of daily living of stroke patients with mild paralysis

[Purpose] The trunk muscles frequently become weak after stroke, thus impacting overall activities of daily living. However, activities of daily living items closely related with trunk strength remain unclear. This study aimed to clarify the influence of trunk muscle weakness on activities of daily living items. [Subjects] The subjects were 24 stroke patients who fulfilled the following inclusion criteria: first stroke and the absence of severe paralysis, marked cognitive function deterioration, unilateral spatial neglect or apathy. [Methods] According to abdominal strength, the 24 patients were divided into a nonweakness group and a weakness group. For the assessment, we used the stroke impairment assessment set, the Berg balance scale, a simple test for evaluating hand function, grip strength, and functional independence measure scale scores and the results were compared between the groups. [Results] The Berg balance scale score and scores for dressing, toilet use, transfer to bed, and walk items of the functional independence measure were significantly lower in the weakness group than in the nonweakness group. [Conclusion] Our results suggest that weakness of the abdominal muscles adversely impacts the balance of patients with mild stroke as well as their ability to dress, use a toilet, transfer, and walk. Trunk training, including abdominal muscle exercises, can effectively improve the performance of these activities of daily living items.Key words: Stroke, Activities of daily living, Abdominal muscles