Systems consolidation requires postlearning activation of NMDA receptors in the medial prefrontal cortex in trace eyeblink conditioning.

The importance of the hippocampus in declarative memory is limited to recently acquired memory, and remotely acquired memory is believed to be stored somewhere in the neocortex. However, it remains unknown how the memory network is reorganized from a hippocampus-dependent form into a neocortex-dependent one. We reported previously that the medial prefrontal cortex (mPFC) is important for this neocortex-dependent remote memory in rat trace eyeblink conditioning. Here, we investigate the involvement of NMDA receptors in the mPFC in this reorganization and determine the time window of their contribution using chronic infusion of an antagonist into the mPFC, specifically during the postlearning consolidation period. The rats with blockade of the mPFC NMDA receptors during the first 1 or 2 weeks after learning showed a marked impairment in memory retention measured 6 weeks after learning, but relearned normally with subsequent conditioning. In contrast, the same treatment had no effect if it was performed during the third to fourth weeks or during the first day just after learning. The specificity of NMDA receptor blockade was confirmed by the reduced long-term potentiation in the hippocampal-prefrontal pathway in these rats. These results suggest that successful establishment of remotely acquired memory requires activation of NMDA receptors in the mPFC during at least the initial week of the postlearning period. Such NMDA receptor-dependent processes may mediate the maturation of neocortical networks that underlies permanent memory storage and serve as a way to reorganize memory circuitry to the neocortex-dependent form

Proton Magnetic Resonance Spectroscopy in Patients with Migration Disorders

Proton Magnetic Resonance Spectroscopy (1H-MRS) can be used to detect cerebral metabolites including N-acetylaspartate (NAA)，creatine (Cr) and choline (Ch). Hence，clinical applications of this method for neuropediatric diseases can be expected. However，regarding neuronal migration disorders，there have been only a few reported studies. We therefore examined the lH-MRS in six patients with migration disorders，ages ranged from 8months to 28years 10months with a mean of 10years 10months. Investigation was performed using Magnetom H15 (Siemens) with a repetition time of 1500 msec and an echo time of 270msec. The ratio of NAA/Cr，Ch/Cr were examined. The volume of interest with the size of 2 × 2 × 2 ～ 3 × 3 × 5cm3 was chosen in the area including lesions，and a contralateral area without lesions was also investigated. Results were as follows. 1) The ratio of NAA/Cr was low in the area with lesions in all 6cases; 1.41，1.95，2.27 and 1.71 in cases with heterotopic gray matter，0.99 in one case with polymicrogyria，an d 1.30 in one case with hemimegalencephaly，contrasted with a contralataral area without lesions: 1.89， 2.89，2.87，2.55，3.26，2.03，respectively. 2) The ratio of Ch/Cr showed no consistent difference between the area including lesions and contralataral area without lesions. Our findings of a decreased NAA/Cr ratio can be inferred to reflect the decreased numbers of neuronal cell population，or reduced metabolism in the lesions

誌上パネル Debate「胸椎OPLLに対する術式選択」 : II. Discussion (1)

金沢大学医学部附属病院リハビリテーション部学会抄

誌上パネル Debate「胸椎OPLLに対する術式選択」 : III. Discussion (2)

金沢大学医学部附属病院リハビリテーション部学会抄

Expression of Hyaluronidase-4 in a Rat Spinal Cord Hemisection Model

Study DesignExamination of hyaluronidase-4 (Hyal-4) expression in a rat spinal cord hemisection model.PurposeTo determine the status of Hyal-4 expression after hemisection of the spinal cord, and the relationship between its expression and that of chondroitin sulfate proteoglycans (CSPGs).Overview of LiteratureCSPGs are expressed at the site of spinal cord injury and inhibit axon regeneration. Administration of exogenous chrondroitinase ABC (ChABC), derived from bacteria, digested CSPGs and promoted axonal regrowth. Using a rat hemisection model, we have demonstrated peak CSPGs levels at by 3 weeks after injury but then decreased spontaneously. Could there be an endogenous enzyme similar to ChABC in the spinal cord? It has been suggested that Hyal-4 is involved in CSPG degradation.MethodsA rat hemisection model was prepared and spinal cord frozen sections were prepared at 4 days and 1, 2, 3, 4, 5, and 6 weeks post-cordotomy and stained for CSPGs and Hyal-4 and subjected to Western blotting.ResultsCSPGs appeared at the injury site at 4 days after hemisection, reached a peak after 3 weeks, and then decreased. Hyal-4 was observed around the injury site from 4 days after cordotomy and increased until after 5-6 weeks. Double staining showed Hyal-4 around CSPGs. Western blotting identified a band corresponding to Hyal-4 from 4 days after hemisection.ConclusionsHyal-4 was expressed in a rat hemisection model in areas surrounding CSPGs, and as its peak was delayed compared with that of CSPGs. These results suggest the involvement of Hyal-4 in the digestion of CSPGs

Outcome of posterior lumbar interbody fusion for L4-L5 degenerative spondylolisthesis

Background: Posterior lumbar interbody fusion (PLIF) has become the standard in the treatment for degenerative spondylolisthesis since improvement of spinal instrumentation However, few published studies have reported long term outcomes of PLIF using a same surgical procedure. The purpose of this study is to evaluate a long term outcome of PLIF using a same surgical procedure for L4-L5 degenerative spondylolisthesis. Materials and Methods: Out of 45 patients who underwent L4-L5 PLIF for degenerative spondylolisthesis between 1995 and 2003, 37 patients (16 males and 21 females) were evaluated in this study. Mean age was 61.8 years. The average followup period was 121 months. We evaluated % slip, lordosis at L4/L5, lumbar lordosis, Japanese Orthopedic Association\u27s (JOA) score and adjacent segment degeneration. Results: The % slip significantly improved from an average of 17.0% before surgery to 9.7% at the last followup. Lordosis at L4/L5 averaged 3.6° before surgery, 8.2° after surgery and 6.9° at the last followup. Although patients experienced some loss of correction at last followup, their lordosis at L4/L5 at last followup still was significantly different from their lordosis at L4/L5 before surgery. Lumbar lordosis did not significantly change. Mean JOA score was 13.4 before surgery and 24.5 at the last followup; mean recovery ratio was 71.2%. Adjacent segment degeneration occurred in 40.5% of patients, almost all of which occurred in the cranial adjacent segment. Three patients (8.1%) required reoperation due to adjacent segment degeneration, at an average of 76 months after their initial surgery. Conclusions: With more than 10-year followup after L4-L5 PLIF for degenerative spondylolisthesis, the adjacent segment degeneration occurred in 40.5% and reoperation was required in 8.1%. © 2015, Medknow Publications Pvt Ltd. All rights reserved

Regulation of DMD pathology by an ankyrin-encoded miRNA

<p>Abstract</p> <p>Background</p> <p>Duchenne muscular dystrophy (DMD) is an X-linked myopathy resulting from the production of a nonfunctional dystrophin protein. MicroRNA (miRNA) are small 21- to 24-nucleotide RNA that can regulate both individual genes and entire cell signaling pathways. Previously, we identified several mRNA, both muscle-enriched and inflammation-induced, that are dysregulated in the skeletal muscles of DMD patients. One particularly muscle-enriched miRNA, miR-486, is significantly downregulated in dystrophin-deficient mouse and human skeletal muscles. miR-486 is embedded within the <it>ANKYRIN1(ANK1) </it>gene locus, which is transcribed as either a long (erythroid-enriched) or a short (heart muscle- and skeletal muscle-enriched) isoform, depending on the cell and tissue types.</p> <p>Results</p> <p>Inhibition of miR-486 in normal muscle myoblasts results in inhibited migration and failure to repair a wound in primary myoblast cell cultures. Conversely, overexpression of miR-486 in primary myoblast cell cultures results in increased proliferation with no changes in cellular apoptosis. Using bioinformatics and miRNA reporter assays, we have identified platelet-derived growth factor receptor β, along with several other downstream targets of the phosphatase and tensin homolog deleted on chromosome 10/AKT (PTEN/AKT) pathway, as being modulated by miR-486. The generation of muscle-specific transgenic mice that overexpress miR-486 revealed that miR-486 alters the cell cycle kinetics of regenerated myofibers <it>in vivo</it>, as these mice had impaired muscle regeneration.</p> <p>Conclusions</p> <p>These studies demonstrate a link for miR-486 as a regulator of the PTEN/AKT pathway in dystrophin-deficient muscle and an important factor in the regulation of DMD muscle pathology.</p