The function of the microtubule-associated protein tau is variably modulated by graded changes in glycogen synthase kinase-3beta activity.

The microtubule-associated protein tau favors microtubule nucleation and stabilization and plays a role in the elongation of axons. We have investigated the ability of glycogen synthase kinase-3beta (GSK-3beta) to control tau-induced processes outgrowth. Tau-transfected Chinese hamster ovary (CHO) cells developed processes containing microtubule bundles after cytochalasin treatment, but a significant reduction in the number of cells harboring processes was observed in tau/GSK-3beta-co-transfected cells. Lithium, an inhibitor of GSK-3beta, counteracted in a dose-dependent manner this inhibitory effect of GSK-3beta. These findings suggest that GSK-3beta modulates in a graded manner the ability of tau to control the microtubule-dependent induction of cell processes.

Calcium binding protein calcyphosine in dog central astrocytes and ependymal cells and in peripheral neurons.

Calcyphosine is a calcium binding protein discovered in the dog thyroid in 1979. Calcyphosine mRNA and immunoreactivity were detected using Western and Northern blotting in the cerebral cortex, cerebral white matter and cerebellum. Using immunohistochemistry and in situ hybridization, both are present in ependymal cells, choroid plexus cells and several types of astrocytes of the subependymal cerebral layer, the cerebellar Bergmann layer, the retinal ganglion cell layer, the optic nerve and the posterior pituitary. Both are also present in neurons of nasal olfactory mucosa, enteric Auerbach and Meissner plexuses, orthosympathic and spinal cord ganglia as well as in endocrine cells of neural crest origin in the adrenal medulla. Calcyphosine immunoreactive astrocytes were also present mainly in hemispheric cerebral gray and white matter, hemispheric subcortical structures, brain stem and spinal cord. These results show that calcyphosine is a characteristic calcium binding protein of astrocytes and ependymal cells in the central nervous system and of neurons in the peripheral nervous system. This is of interest in view of the importance of calcium regulation in these cells, and since calcyphosine a calcium binding protein phosphorylated by cAMP dependent process, may be an intermediate between cAMP and inositol phosphate cascades.

The pathology of infantile hypertrophic pyloric stenosis after healing.

INTRODUCTION: Infantile hypertrophic pyloric stenosis (IHPS) is a common surgical affection of unknown etiology. The muscular hypertrophy is known to resolve within a few months after pyloromyotomy (PM). The pathology of IHPS has been studied extensively at the time of PM, but the fate of the pylorus after healing remains unknown. MATERIALS AND METHODS: We had the rare opportunity to study two pyloric biopsy specimens obtained 4 months and 2 years (respectively) after an uncomplicated PM for IHPS. They were compared with the initial specimen in one case, with 26 other specimens of IHPS, and with five normal controls. Immunohistochemistry using the avidin-biotin complex (ABC) system was performed for S-100 and nerve growth factor receptor, as markers for the enteric nervous system, and for the tyrosine kinase receptor c-kit, as a marker for the interstitial cells of Cajal (pacemaker cells). NADPH-diaphorase histochemistry was performed as a marker for the neuronal enzyme nitric oxide synthase, which produces the inhibitory neurotransmitter nitric oxide. RESULTS: In both cases of IHPS, after healing, the circular musculature was not hypertrophic. For all markers studied, the distribution appeared similar to that in the normal pylorus. In contrast, all specimens obtained at the time of PM displayed a severe reduction of the different markers in the hypertrophic musculature. DISCUSSION: The pathological features observed in the circular layer in IHPS appear to resolve within a few months after PM. This suggests that the involvement of the enteric nervous system in IHPS might be milder than generally assumed. The etiology remains obscure, but our occasional observations may provide new insight into the pathophysiology of IHPS, and are in agreement with the excellent longterm clinical outcome for IHPS.

Calcineurin (phosphatase 2B) is present in neurons containing neurofibrillary tangles and in a subset of senile plaques in Alzheimer's disease.

The accumulation of hyperphosphorylated tau species in neurons in Alzheimer's disease (AD) might result from a relative decrease in their content of protein phosphatases. In this study we have investigated the immunocytochemical distribution of calcineurin (phosphatase 2B) in the hippocampus and temporal cortex of human control subjects and in AD. Calcineurin was strongly expressed in neuronal perikarya and dendrites but only weakly in white matter tracts, both in controls and in AD. The distribution of calcineurin was preserved in AD. By double-immunolabelling with calcineurin antibodies and the AT8 antibody to paired helical filament-tau, it was observed that a strong calcineurin immunoreactivity was still present in many neurons containing neurofibrillary tangles (NFT). Calcineurin was present in dystrophic neurites in some senile plaques (SP) located in the hippocampal formation but more rarely in neocortical areas; this calcineurin immunoreactivity did not always overlap with the tau immunoreactivity in SP. These results suggest that development of NFT in most neurons does not result from a major decrease of calcineurin expression.