Treatment with methylazoxymethanol at different gestational days: physical, reflex development and spontaneous activity in the offspring

Pregnant rats were injected with a single dose of methylazoxymethanol (MAM, 25 mg/kg) on gestational day 14, 15, 16, 17, 18 or 19 and offspring were tested for their physical development, reflex development and spontaneous activity. MAM treatment did not affect gestational and litter parameters at any of the time of administration studied. Treatment at gestational day 14 (GD14) had the most severe effect on functional neurodevelopment until weaning: righting reflex at surface, chimney test, horizontal wire test resulted altered. Administration at GD15, 16, 18, 19 did not affect the performance in these tests. Offspring treated at GD17 showed a delayed eye opening and an impaired performance in the horizontal wire test. When tested at 50 days of age on the rotarod, all the treated groups performed worse than controls with the exception of GD19 treated offspring. Administration at GD14 and GD15 resulted in increased spontaneous activity of the offspring at 21 days but not at 60 days of age. Different degrees of microencephaly were observed for all treated groups. The results indicate that alterations of physical and behavioral development induced by MAM treatment are dependent on the time of MAM administration, and specific behavioral tests are able to detect different abnormalities and differentiate among treatment groups. Some alterations observed in MAM rats undergo to adaptive changes during maturation of the CNS.     

Dibutyryl-cAMP induces SNAP-25 translocation into the neurites in PC12.

SNAP-25 immunoreactivity was translocated into the endings of the processes induced in PC12 cells by dibutyryl-cAMP-treatment. Conversely, the protein was not present in the endings of the processes seen after NGF-treatment unless dibutyryl-cAMP was used simultaneously. This redistribution of SNAP-25 immunoreactivity appeared to be dependent upon new protein synthesis. Finally, dibutyryl-cAMP was capable of inducing SNAP-25 expression.     

Pharmacological modulation of neuropeptides in peripheral mononuclear cells.

The concentrations of beta-endorphin and cholecystokinin were measured in fresh resting peripheral mononuclear cells obtained from rats and human subjects in basal conditions and after different pharmacological treatments. Both in the human and the rat, beta-endorphin concentrations in mononuclear cells, increased after treatment with serotoninergic agonists, decreased after dopaminergic or GABAergic drugs, while the respective antagonists exerted the opposite effect. In vitro, serotoninergic and GABAergic compounds confirmed their roles in the modulation of beta-endorphin in mononuclear cells. Cholecystokinin was never affected by the pharmacological treatments.     

The identity of the calcium-storing, inositol 1,4,5-trisphosphate-sensitive organelle in non-muscle cells: calciosome, endoplasmic reticulum ... or both?

Although the initial phase of receptor-mediated Ca2+ signaling, involving Ca2+ release from intracellular stores by inositol 1,4,5-trisphosphate, is relatively well characterized, the nature of the organelle releasing Ca2+ is a controversial subject. At issue is the question of whether Ca2+ is released from the endoplasmic reticulum, or from a more specialized organelle called the 'calciosome'. In this review, we attempt to analyse the arguments for and against these two views, and attempt to reconcile some of the apparently conflicting findings by proposing a hypothetical model of the inositol 1,4,5-trisphosphate-sensitive Ca2+ pool.     

Familial association of intracranial aneurysms and cervical artery dissections.

BACKGROUND AND PURPOSE: The familial occurrence of intracranial aneurysms and cervical artery dissections has been described in different families and supports the hypothesis that a primary arteriopathy may play a role in the pathogenesis of these disorders. Although the basis for this arteriopathy is generally not believed to be similar among cases of intracranial aneurysms and cervical artery dissections, several similarities exist in the epidemiology of these disorders and a common underlying arterial abnormality may be suspected. SUMMARY OF REPORTS: The medical records of all 175 patients with spontaneous dissections of the cervical arteries who were seen at the Mayo Clinic between 1970 and 1989 were reviewed to identify families in which intracranial aneurysms and cervical dissections coexisted. Three families were identified in which intracranial aneurysms and cervical artery dissections were observed among siblings. These families are described in detail. CONCLUSIONS: The familial occurrence of intracranial aneurysms and cervical artery dissections within the same families provides support to the importance of a common underlying arteriopathy in the pathogenesis of both these disorders. The underlying vascular defect may, at least in some cases, be inherited.     

Local demineralization as a model for bone strength reductions in lytic transcortical metastatic lesions.

The structural consequences of bone density changes associated with lytic metastatic lesions were investigated using an experimental model of regular, lytic metastatic lesions in bone. Circular holes were drilled in the mid-diaphyseal cortex of paired adult canine femora. The region around the defect was demineralized in one bone of each pair with 0.8 N HCl. Specimens were tested to failure in four-point bending. Defect size was determined from conventional planar radiographs as the maximum apparent defect diameter divided by the periosteal diameter. Demineralization resulted in irregular defect geometries, which increased the maximum defect dimension 33% to 57% with respect to the original drill hole diameter. Demineralization resulted in additional strength reductions beyond those expected from the original drill hole alone. Despite the irregular demineralization patterns observed, strength reductions were in close agreement with those predicted from data for regular, nondemineralized holes (r2 = 0.93). The results demonstrate that irregular diaphyseal defect borders may not require more complex fracture risk predictors than can be determined from analytic and experimental studies of regular defect geometries. Our results also demonstrate that errors of over 100% can occur when measuring diaphyseal defect size from radiographs that are not optimally aligned with respect to the defect.     

Basic fibroblast growth factor prevents thalamic degeneration after cortical infarction

In the focal infarction model of the rat middle cerebral artery (MCA), the thalamus of the occluded side becomes gradually atrophic, mainly because of retrograde degeneration. We determined whether basic fibroblast growth factor (bFGF) administered intracisternally could prevent this thalamic atrophy. We occluded the left MCA through a small cranial opening, and animals were then divided into two groups. One group received intracisternal injections of recombinant bFGF (1 microgram dissolved in 0.1 ml of saline with 2% rat serum) starting 1 day after occlusion and repeated once a week to a total dose of 4 micrograms by four injections. The other group received vehicle solution by the same schedule. The animals were perfused and fixed at 28 days after occlusion, and histological examination was made at the level of the caudoputamen and thalamus. In the bFGF-treated rats, the area of the posterior ventral thalamus of the occluded side was 93% of that of the contralateral side, i.e., significantly larger than in the normal saline-treated rats (75%, p less than 0.01). The infarction size was not statistically different in the two groups. Microscopic observation indicated that normal-saline-treated animals showed shrinkage and disappearance of thalamic neurons, whereas bFGF-treated groups showed preservation of thalamic neurons. Computerized analysis of the cell size substantiated this observation. To assess the effect of bFGF on astrocytes, bFGF or vehicle solution was injected into normal rats, and their histology was evaluated at 1, 2, and 4 weeks after injection. The bFGF-injected group showed a significant increase in glial fibrillary acidic protein-positive astrocytes in the brain tissue facing the ventriculocisternal system.(ABSTRACT TRUNCATED AT 250 WORDS)     

Glutamate receptor antagonists block cocaine-induced convulsions and death.

The involvement of excitatory amino acid (EAA) receptors in mediation of the toxic effects of cocaine was studied in male ICR mice. Cocaine HCl (90 mg/kg, IP) induced seizures in 95% and death within 24 h in 68% (n = 135) of the animals. There was a significant correlation (r = .54) between the time to onset of convulsions and the time to death in mice which died within 30 min of injection (n = 84). Pretreatment with selected EAA receptor antagonists 15 min prior to cocaine differentially blocked cocaine toxicity. Selective N-methyl-D-aspartic acid (NMDA) receptor antagonists (MK-801, dextrorphan, CPP) decreased both the incidence of seizures and mortality. A nonselective EAA antagonist, kynurenic acid, decreased lethality in doses which did not reduce convulsions. A similar action was observed following pretreatment with the selective kainic acid/AMPA receptor antagonist, GDEE. Antagonists at EAA receptors can provide significant protection against cocaine-induced toxicity. Moreover, the data provide evidence for the involvement of both NMDA and non-NMDA receptor subtypes in aspects of cocaine toxicity.