Abnormal alterations in the Ca2+/CaV1.2/calmodulin/caMKII signaling pathway in a tremor rat model and in cultured hippocampal neurons exposed to Mg2+-free solution

Voltage-dependent calcium channels (VDCCs) are key elements in epileptogenesis. There are several binding-sites linked to calmodulin (CaM) and several potential CaM-dependent protein kinase II (CaMKII)-mediated phosphorylation sites in CaV1.2. The tremor rat model (TRM) exhibits absence‑like seizures from 8 weeks of age. The present study was performed to detect changes in the Ca2+/CaV1.2/CaM/CaMKII pathway in TRMs and in cultured hippocampal neurons exposed to Mg2+‑free solution. The expression levels of CaV1.2, CaM and phosphorylated CaMKII (p‑CaMKII; Thr‑286) in these two models were examined using immunofluorescence and western blotting. Compared with Wistar rats, the expression levels of CaV1.2 and CaM were increased, and the expression of p‑CaMKII was decreased in the TRM hippocampus. However, the expression of the targeted proteins was reversed in the TRM temporal cortex. A significant increase in the expression of CaM and decrease in the expression of CaV1.2 were observed in the TRM cerebellum. In the cultured neuron model, p‑CaMKII and CaV1.2 were markedly decreased. In addition, neurons exhibiting co‑localized expression of CaV1.2 and CaM immunoreactivities were detected. Furthermore, intracellular calcium concentrations were increased in these two models. For the first time, o the best of our knowledge, the data of the present study suggested that abnormal alterations in the Ca2+/CaV1.2/CaM/CaMKII pathway may be involved in epileptogenesis and in the phenotypes of TRMs and cultured hippocampal neurons exposed to Mg2+‑free solution.

Meningeal alveolar soft part sarcoma confirmed by characteristic ASPCR1-TFE3 fusion

Sarcoma metastatic to the brain is uncommon and rarely occurs as the initial manifestation of tumor. Alveolar soft part sarcoma (ASPS) is a rare but well-studied subtype of sarcoma. A 39-year-old man presented with seizures due to a left temporal meningeal-enhancing lesion with striking brain edema on MRI. The patient underwent neurosurgical resection for suspected meningioma. Histology showed large tumor cells clustering and forming small nests, in places with pseudoalveolar pattern. Diastase-resistant periodic acid-Schiff revealed very rare granular and rod-like cytoplasmic inclusions. Immunohistochemistry showed convincing positivity only with vimentin and smooth muscle actin. The histological features were strongly suggestive of ASPS. At the molecular level RT-PCR and sequencing analysis demonstrated ASPCR1-TFE3 fusion confirming the histological diagnosis of ASPS. There was no evidence of primary extracranial tumor by physical examination and on chest and abdominal CT scan 11 months after presentation. ASPS typically arise from the soft tissues of the extremities and develop multiple metastatic deposits usually with a long clinical course. This case may represent primary meningeal ASPS although metastatic deposit from an undiscovered primary site cannot be entirely excluded.