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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 Ca 2ϩ 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 Ca 2ϩ influx was decreased by 8-(4-chlorophenylthiol)-guanosine-3Ј,5Ј-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 I␤ mRNA, but no translation of PKG I␣ mRNA. Therefore, we concluded that the cyclic GMP/PKG system prevents OLC excitotoxicity. Key Words: Non-NMDA glutamate receptors-Oligodendroglia-Cyclic GMP-Ca 2ϩ influx-Cyclic GMP-dependent protein kinase-Protein phosphatases.

BackgroundDue to the nature of neurodegenerative disorders, patients with primary progressive aphasia develop cognitive impairment other than aphasia as the disorder progresses. The progression of logopenic variant primary progressive aphasia (lvPPA), however, has not been well described. In particular, praxic disorders and semantic memory deficits have rarely been reported.Case presentationsWe report three patients in the initial stage of lvPPA who subsequently developed apraxia in the middle stage and developed clinically evident semantic memory deficits in the advanced stages.ConclusionsThe present case series suggests that some patients with lvPPA develop an atypical type of dementia with apraxia and semantic memory deficits, suggesting that these cases should be classified as a type of early-onset Alzheimer’s disease.

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.