Temporal pattern of AP-1 DNA-binding activity in the rat hippocampus following a kindled seizure.

DNA binding by transcripton factor AP-1 was enhanced remarkably following kindling stimulation in rat amygdala. Maximum increase occurred 2 h after stimulation with return to baseline within 24 h. Supershift and western analyses revealed that 38,000 mol. wt Fos-related antigen and JunD were the main components of the evoked AP-1 complexes at the time their induction reached maximum. AP-1 induction 2 h after the last kindling stimulation was more prominent in samples from previously kindled rats than in those from non-kindled rats. This study sought to establish the role of AP-1 in plastic changes of the hippocampus associated with kindling. Male Sprague-Dawley rats were kindled from the left amygdala until they exhibited Racine15 class 5 generalized seizures. Nuclear proteins were extracted from dorsal hippocampi obtained from 0 to 24 h after final stimulations. From these, we evaluated the temporal pattern of DNA binding by AP-1 using a gel mobility-shift assay with a 32P-labelled AP-1 probe. Supershift and western analyses were added to investigate components of the seizure-evoked AP-1 complexes. Our results suggest that the basal level of AP-1 complexes is not associated with the seizure susceptibility in kindling. However, development of kindling appears to facilitate stimulus-evoked AP-1 induction, probably via plastic changes in the central nervous system. AP-1 may mediate such changes by regulating expression of certain genes.

Effect of chronic ipsapirone treatment on the density of 5-HT1A receptors and 5-HT1A receptor mRNA in discrete regions of the rat brain.

There is increasing evidence that the 5-hydroxytryptamine (HT)1A partial agonist ipsapirone is an effective anxiolytic/antidepressant agent, although its mechanism of action is not clear. In this study, we investigated the effects of chronic ipsapirone treatment (5 or 10 mg/kg; twice daily, 3 weeks) on 5-HT1A receptor density 8-hydroxy-2-(di-n-propyl amino) tetralin (8O H-DPAT) binding and the level of its mRNA (in situ hybridization) in various regions of the rat (male Wistar 250 g) brain. Receptor density was reduced in the frontal cortex, but did not change significantly in the hippocampus and dorsal raphe nucleus. The level of receptor mRNA was unchanged in each of these brain regions. The present results suggest that the clinical anxiolytic effects of ipsapirone may be mediated partly by postsynaptic action on serotonergic transmission in the frontal cortex, but not in the hippocampus or dorsal raphe nuclei.

Levodopa induces AP-1 and CREB DNA-binding activities in the rat striatum.

In order to elucidate the effect of levodopa and bromocriptine on the DNA-binding activities of transcription factors, AP-1 and CREB DNA-binding activities were investigated using gel-shift assay. Intraperitoneal administration of 100 mg/kg levodopa with 50 mg/kg benserazide in rats increased both AP-1 and CREB DNA-binding activities in the dorsolateral aspect of the striatum. The major proteins composing the increased AP-1 were JunB and JunD. Bromocriptine at doses of 2.5 and 5.0 mg/kg, however, did not increase these binding activities. Present results suggest that levodopa but not bromocriptine induces these transcription-regulating proteins in the striatum with normal dopaminergic functioning.

[Avellis syndrome in systemic rheumatoid vasculitis].

A 74-year-old man presented sudden onset hoarseness and dysphagia. Two months before this event, he had developed arthralgia of the shoulders, elbows, hands and foot and pleuritis which had been alleviated by a treatment with prednisolone. On admission, the patient could not phonate nor swallow at all. His soft palate was elevated at the right side. The uvula moved left when the patient tried to speak. Laryngoscopic examination revealed the paralysis of right vocal cord. The erythrocyte sedimentation rate (79mm/1h), C-reactive protein (5.3mg/dl), rheumatoid factor (310 IU/ml) and Clq-binding immune complex (4.5 micrograms/ml) were elevated. Hepatitis C virus antibody titer was more than 10.8 IU/l. Anti-nuclear antibody was 1:20 (normal < 1:20) and anti-neutrophil cytoplasmic antibody (p-ANCA) was positive. Blood study also revealed the evidences of hemolytic anemia and hypoproteinemia. Hepatitis B virus markers, cryoglobulin, anti-ds DNA, anti-Sm, anti-RNP, anti-SS-A, anti-SS-B antibodies were negative. Magnetic resonance imaging of the brainstem was normal. A sural nerve biopsy revealed patchy demyelination of the fascicles. The teasing of nerve fibers showed segmental demyelination. Chest X-ray showed the interstitial pneumonia and pleuritis in the right lower lung. Otological examination revealed the bilateral secretory otitis media. A treatment with high dose prednisolone, ciclosporin and cyclophosphamide was partially effective. However we could not continue these medication because of the induction of liver damage. The patient died of multi-organ failure around a year after the emergence of aphonia and dysphagia. The autopsy specimen of the right vagus nerve showed the similar patchy damage of nerve fibers as was observed in the biopsied sural nerve. The present case was diagnosed as systemic rheumatoid vasculitis. The syndrome of aphonia and dysphagia due to paralysis of the unilateral soft palate and vocal cord is called Avellis syndrome. This syndrome has been reported mainly in relation with the infarction of lateral medulla. The present case shows that Avellis syndrome can be produced by mononeuritis of the vagus nerve.

Does homozygosity advance the onset of dentatorubral-pallidoluysian atrophy?

We confirmed a homozygous type of relatively small expansion of CAG triplet repeats (57 repeats) in the short arm of chromosome 12 in a male patient with dentatorubral-pallidoluysian atrophy (DRPLA) by polymerase chain reaction. He showed early onset (age, 17 years) of DRPLA. There was good correlation of the age of onset with the number of triplet repeats. The homozygous state of the expansion of the triplet repeats was responsible for the early onset and severity of his DRPLA.

Relapsing neuropathy associated with hepatitis C virus infection.

A patient with hepatitis C virus (HCV) infection developed neuropathy characterized by recurrent attacks of anesthesia, dysaesthesia, mild weakness and swelling of the right forearm. Serological examinations suggested an abnormal autoimmune state. HCV infection might produce neuropathy by inducing abnormal autoimmunity.