Shinji Saiki

Cardiac 123I-MIBG scintigraphy can assess the disease severity and phenotype of PD

OBJECTIVE Cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy studies of patients with idiopathic Parkinsons disease (PD) found decreased uptake. Whether this decrease is associated with clinical severity as assessed by the Unified Parkinsons Disease Rating Scale (UPDRS) and the phenotypes of PD has not been determined. METHODS Cardiac MIBG scintigraphy was performed on 34 patients with PD, 7 with multiple system atrophy (MSA), 4 with dementia with Lewy bodies (DLB), and 11 normal controls (NCs). Early and delayed MIBG heart/mediastinum (H/M) ratios were evaluated. PD severity was assessed by the Hoehn and Yahr (H-Y) stage and UPDRS. Patients were grouped in two phenotypes, tremor and postural instability gait difficulty (PIGD)-dominant groups based on UPDRS components. Associations between MIBG uptake and age at onset, UPDRS, and disease phenotype were analyzed in each group. RESULTS The early H/M ratio was significantly lower in patients with PD (1.45+/-0.207) than in the NCs (2.08+/-0.231), and in those with MSA (1.99+/-0.284), but not in those with DLB (1.29+/-0.0435). The delayed H/M ratio for PD (1.33+/-0.276) also was significantly decreased as compared to the ratios for NCs (2.17+/-0.286) and MSA (2.16+/-0.414) but not DLB (1.16+/-0.0949). The early H/M ratio was significantly correlated with both UPDRS score and age at onset, whereas the delayed H/M ratio only was significantly correlated with age at onset. The PIGD-dominant group had significantly higher UPDRS scores and lower H/M ratios than the tremor-dominant group. CONCLUSION Cardiac MIBG scintigraphy can be used to differentiate PD from MSA and NC, and to determine the disease severity and phenotypes of PD.

Non-N-methyl-d-aspartate glutamate receptors mediate oxygen–glucose deprivation-induced oligodendroglial injury

Cells of oligodendroglial lineage are susceptible to oxygen and glucose deprivation. When oligodendrocyte-like cells differentiated from CG-4-immortalized rat O-2A progenitor cells were exposed to hypoxia alone or glucose deprivation alone for 48 h, release of lactate dehydrogenase (LDH) into the culture medium did not increase. However, when cells were deprived of both oxygen and glucose for 6 or 12 h preceding reoxygenation for 2 h, LDH release increased. Adding glucose to the medium protected against cell death and increased lactate production in a concentration-dependent manner. Cell damage induced by deprivation of oxygen and glucose was prevented by calcium-free medium or by non-N-methyl-D-aspartate glutamate receptor (GluR) antagonists, such as 6-cyano-7-nitroquinoxaline-2,3-dione or LY293558, but not by the voltage-dependent calcium channel blocker, nimodipine, or by the N-methyl-D-aspartate GluR antagonist, MK-801. The glutamate concentration in the medium from cells exposed to oxygen-glucose deprivation for 12 h was 49.70+/-3.04 microM/l, which is sufficient to activate GluRs during deprivation of oxygen and glucose. Apoptotic cells detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) or Hoechst 33258 staining did not increase in cells exposed to oxygen-glucose deprivation for 12 h and subsequent reoxygenation for 2 h. No DNA laddering was detected by agarose gel electrophoresis from cells exposed to deprivation of oxygen and glucose. Neither acetyl-YVAD-CHO, an inhibitor of caspase-1-like proteases, nor acetyl-DEVD-CHO, an inhibitor of caspase-3-like proteases, prevented oxygen-glucose deprivation-induced injury. Thus, oxygen and glucose deprivation causes calcium-influx-induced necrotic cell damage in cells of oligodendroglial lineage via non-N-methyl-D-aspartate GluR channels.

Mutation in the CHAC gene in a family of autosomal dominant chorea–acanthocytosis

Writ e Click is restricted to comments about studies published in Neurology ® within the past 8 weeks. The submission below represents an exception because it addresses a genetic sequencing error published in Neurology in 2003. In addition, these Writ e Click submissions will be available as open access to all readers in an effort to further publicize the Correction. In 2003, Saiki et al.1 reported an autosomal dominant transmission of chorea-acanthocytosis (ChAc) that constituted a significant challenge to the generally …

Cyclic GMP/cyclic GMP-dependent protein kinase system prevents excitotoxicity in an immortalized oligodendroglial cell line.

Abstract: Previously, we have demonstrated that excitotoxicity of oligodendrocyte‐like cells (OLC), differentiated from immortalized rat O‐2A progenitor cells (CG‐4 cells), is prevented by cyclic AMP‐elevating agents. We now report that some agents that elevate cyclic GMP prevent OLC excitotoxicity. Kainate‐induced injury was prevented by cyclic GMP analogues (8‐bromo‐cyclic GMP and dibutyryl cyclic GMP), a guanylate cyclase activator [atrial natriuretic peptide (ANP)], and phosphodiesterase inhibitors [3‐isobutyl‐1‐methylxanthine (IBMX), ibudilast, propentofylline, and rolipram]. When both forskolin and 8‐bromo‐cyclic GMP were added, kainate‐induced injury was additively prevented. There was a strong positive correlation between suppression of kainate‐induced Ca2+ influx and prevention of injury by these chemicals. The measurement of intracellular cyclic AMP and cyclic GMP by radioimmunoassay demonstrated the following: an increase of cyclic GMP with treatment with 8‐bromo‐cyclic GMP, dibutyryl cyclic GMP, and ANP; an increase of cyclic AMP with treatment with ibudilast and rolipram; and an increase of both cyclic AMP and cyclic GMP with treatment with IBMX and propentofylline. Kainate‐induced Ca2+ influx was decreased by 8‐(4‐chlorophenylthiol)‐guanosine‐3′,5′‐monophosphate, an activator of cyclic GMP‐dependent protein kinase (PKG), or okadaic acid, an inhibitor of protein phosphatases 1 and 2A. RT‐PCR and western blotting of OLC demonstrated transcription of PKG II gene and translation of PKG Iβ mRNA, but no translation of PKG Iα mRNA. Therefore, we concluded that the cyclic GMP/PKG system prevents OLC excitotoxicity.

Chorea-acanthocytosis associated with Tourettism.

We report on a case of Chorea‐acanthocytosis (ChAc) in association with Tourettism that consisted of motor and vocal tics, attention deficit–hyperactivity disorder, and obsessive–compulsive disorder in addition to the typical symptoms of ChAc. The subject was compared with his elder sister who had the same disease but milder clinical profile and neuroradiological findings. The [18F]‐2‐fluoro‐2‐deoxyglucose positron emission tomography (FDG‐PET) findings did not explain the differences in symptomatology between the patient and his sister, although they may have correlated with severity.

Effect of a paraneoplastic cerebellar degeneration-associated neural protein on B-myb promoter activity.

In this study, we have shown that a paraneoplastic cerebellar degeneration (PCD)-associated antigen, pcd17, binds to a cell cycle-related protein, MRG15. MRG15 derepresses the E2F-responsive B-myb promoter. The pcd17 antigen inhibits the derepression of the B-myb transcriptional activity by MRG15, and, as a result, pcd17 represses the promoter. Delivery of anti-Purkinje cell antibodies (anti-Yo) into the cells inhibits the repression of B-myb promoter activity by pcd17. Because derepression of the B-myb promoter has been implicated in neuronal death, the results suggest the possible role of the antibodies in the pathogenesis of PCD.

Rostral lateral pontine infarction: Neurological/topographical correlations

The authors correlated neurologic features of rostral lateral pontine infarct (rLPI) with lesion location on MRI. rLPI is a motor-sensory stroke presenting as crural monoparesis or crural dominant hemiparesis and segmental superficial or deep sensory disturbances. The dorsolateral pontine base causes crural paresis without supranuclear facial palsy.

Type-2 astrocyte-like cells are more resistant than oligodendrocyte-like cells against non-N-methyl-D-aspartate glutamate receptor-mediated excitotoxicity.

Glutamate causes excitotoxicity via non‐N‐methyl‐D‐aspartate (NMDA) glutamate receptors (GluR) in oligodendrocytes. Because both oligodendrocytes and type 2 astrocytes are differentiated from oligodendrocyte‐type 2 astrocyte (O‐2A) progenitor cells, we investigated whether astrocytes are also vulnerable to non‐NMDA GluR‐mediated excitotoxicity. For these studies, oligodendrocyte‐like cells (OLC) and type 2 astrocyte‐like cells (2ALC) were derived from CG‐4 cells, an immortalized rat O‐2A progenitor cell line. About 50% of 2ALC were positive for glial fibrillary acidic protein and 90% were positive for A2B5, verifying that these cells have an type 2 astrocytic phenotype. A 24‐hr exposure of OLC to 2 mM kainate, an activator of non‐NMDA GluR, caused cell damage as shown by the release of lactate dehydrogenase. The extent of kainate‐induced OLC damage was increased by cyclothiazide. In contrast, exposure of 2ALC to 2 mM kainate alone did not induce injury, though mild 2ALC injury was elicited by exposure to 2 mM kainate plus 100 μM cyclothiazide. Furthermore, we found that the kainate induced Ca2+ uptake by 2ALC was 27.5% of that induced by kainate in OLC. Finally, both OLC and 2ALC expressed non‐NMDA GluR subunit mRNAs, including GluR2, GluR3, GluR4, GluR6, GluR7, KA1, and KA2, but quantitative Western blot analysis revealed higher immunodetectable GluR2 and lower immunodetectable GluR3 and GluR4 in 2ALC than in OLC. Together, these results suggest that astrocytes are relatively resistant to non‐NMDA GluR‐mediated excitotoxicity because they have a higher expression of GluR2 and lower expression of GluR3 and GluR4.