The chromosome 16q‐linked autosomal dominant cerebellar ataxia (16q‐ADCA): A newly identified degenerative ataxia in Japan showing peculiar morphological changes of the Purkinje cell

The chromosome 16q22.1‐linked autosomal‐dominant cerebellar ataxia (16q‐ADCA) is a form of spinocerebellar ataxia (SCA) common in Japan. It is clinically characterized by late‐onset purely cerebellar ataxia. The neuropathologic hallmark of 16q‐ADCA is degeneration of Purkinje cells accompanied by an eosinophilic structure which we named “halo‐like amorphous materials”. By immunohistochemistry and electron microscopy, the structure has been so far found to contain two components: the somatic sprouts from the Purkinje cells and presynaptic terminals of unknown origin. As far as we are aware, this peculiar morphological change of Purkinje cells has not been previously described. Further investigations may disclose unique pathological processes in SCA.     

Enhancement of apomorphine-induced penile erection in the rat by a selective alpha(1D)-adrenoceptor antagonist

1. Effects of A-322312 (alpha(1B)-adrenoceptor (AR) antagonist), A-119637 (alpha(1D)-AR antagonist), prazosin (non-selective alpha(1)-AR antagonist), and yohimbine (alpha(2)-AR antagonist) were studied in rat corpus cavernosum (CC) and cavernous artery (Acc) preparations. Effects of intracavernous (i.c.) or intraperitoneal (i.p.) administration of alpha(1)-AR antagonists on apomorphine-induced erections were investigated. 2. A-119637 attenuated electrically induced contractions in isolated CC (-logIC(50); 8.12+/-0.15), and relaxed noradrenaline (NA)-contracted preparations by more than 90% at 10(-7) M. At the same concentration, the -logEC(50) value for NA in Acc was altered from 6.79+/-0.07 to 4.86+/-0.13. In the CC and Acc, prazosin similarly inhibited contractile responses. 3. Inhibitory effects of A-322312 (10(-7) M) in electrically activated CC were 32.3+/-5.1%, whereas no effect on concentration-response curves for NA was observed in the Acc. Yohimbine (10(-8) M and 10(-7) M), enhanced electrically-induced contractions in isolated CC by 20 to 50%. At 10(-6) M, inhibitory effects of yohimbine were obtained. 4. A-119637 (0.3 micromol kg(-1), i.p.) tripled the number of erections, and produced a 6 fold increase in the duration of apomorphine-induced erectile responses. A-322312, prazosin, or yohimbine did not enhance erections induced by apomorphine. None of the alpha(1)-AR antagonists significantly increased ICP upon i.c. administration. Decreases in blood pressure were seen with A-119637 and prazosin. 5. The present findings show that there is a functional predominance of the alpha(1D)-AR subtype in the rat erectile tissue, and that blockade of this receptor facilitates rat penile erection induced by a suboptimal dose of apomorphine.     

Brain ischemia--regenerative therapy using human neural stem cells]

The mortality of stroke is still the those of single organs. Even if patients survive the brain attack they often suffer from not only motor functional disability but also psychiatric problems such as post-stroke depression and decrease in spontaneity. The stoke is the number one cause of the bed-ridden state "Netakiri". Presently only anti-thrombotic and anti-oxidative stress therapies are available and the ischemic core destroyed immediately after the stroke could never be rescued. We have started to study the basic aspect of transplantation therapy of cerebral infarction using neural stem cells. Using a focal ischemic model of the gerbil by repeated occlusion of the unilateral carotid artery, we grafted human neural stem cells which were cultured and proliferated for a long period. Grafted animals showed significant and marked improvement in all three functions including motor, sensory and cognitive functions associated with a significant reduction of infarction volume. Synaptic contacts between neurons from grafted human neural stem cells and host neurons were confirmed by immuno-electron microscopy. This is a very encouraging report although it is necessary to elucidate the precise mechanism of the functional recovery or the effect of neural stem cell transplantation.     

Dual impairment of GABAA- and GABAB-receptor-mediated synaptic responses by autoantibodies to glutamic acid decarboxylase

Anti-glutamate decarboxylase autoantibodies (GAD-A) are associated with a group of patients with progressive cerebellar ataxia. We reported previously that cerebellar GABA(A)-mediated synaptic transmission was presynaptically depressed by GAD-A in the cerebrospinal fluid (CSF). Using whole-cell recording of rat cerebellar slices, we found in the present study that CSF immunoglobulins from ataxic patients reduced gamma-aminobutyric acid (GABA) release from cerebellar interneurons, thereby attenuating presynaptic inhibition on neighboring excitatory synapses through GABA(B) receptors (GABA(B)Rs). Our results suggest that in in vitro slices, GAD-A elicited the pathophysiological action of reduction in GABA release, which subsequently resulted in dual synaptic impairment in the cerebellar circuit, by depression of GABA(A) receptor (GABA(A)R)-mediated inhibitory synaptic transmissions, and attenuation of GABA(B) receptor-mediated inhibition of excitatory transmissions.     

Distal myopathy with rimmed vacuoles: novel mutations in the GNE gene

The authors present three novel missense mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene, the causative gene for hereditary inclusion body myopathy, in Japanese patients with distal myopathy with rimmed vacuoles. Seven out of nine patients had homozygous V572L mutation, one was a compound heterozygote with C303V and V572L mutations, and the remaining patient bore homozygous A631V mutation.