Reelin-immunoreactivity in the hippocampal formation of 9-month-old wildtype mouse: effects of APP/PS1 genotype and ovariectomy

Reelin, an extracellular matrix protein has an important role in the migration, correct positioning and maturation of neurons during development. Though it is generally down-regulated in the postnatal period, expression of this large glycoprotein continues in the adult brain in some cell populations. In the present study, we examined the distribution of reelin-immunoreactivity (-ir) in the hippocampal formation of 9-month-old wildtype mice (WT). Then, reelin-ir in normal mice was compared to that of transgenic mice (APP/PS1) carrying mutated human APP and PS1 genes, which are linked to the familial form of Alzheimer's disease (AD). The APP/PS1 mice were additionally burdened with a second risk factor for AD, namely depletion of circulating gonadal hormones by ovariectomy (APP/PS1 + OVX). The analyses revealed that in adult WT reelin-ir is expressed by Cajal-Retzius cells and a subgroup of interneurons throughout the hippocampal formation. In addition, layer II projection neurons in the lateral entorhinal subfields are reelin-ir. Interestingly, ovariectomy decreases the number of reelin-ir cells in the hilus in WT mice, whereas AD-related genotype alone induces only a non-significant reduction. Unexpectedly, additional stress, e.g., depletion of gonadal hormones, does not aggravate the slight reduction in the reelin cell number in the APP/PS1 mice. We propose that the changes in normal reelin-ir are linked to disturbances in repair mechanisms in which APP/PS1 and gonadal hormones are involved and which are perturbed in neurodegenerative conditions, namely AD.     

Muscle spindles in denervated and reinnervated m. soleus of the rat. I. Changes in number, distribution and length of muscle spindles]

After a transient or permanent unilateral denervation of the soleus muscle of the rat the number, distribution and length of muscle spindles were determined. The results were compared with those of the contralateral innervated muscle and with the data received from investigating soleus muscles of normal uninjured rats. Denervation (with or without reinnervation) reduces the number of muscle spindles by nearly 50%. The typical uniform distribution of muscle spindles in the muscle remains almost unchanged. The remaining muscle spindles grow longer. The same findings are observed in the contralateral still innervated muscles, too. Consequently a comparison of the denervated (reinnervated) muscle exclusively with its contralateral muscle does not show different counts of muscle spindles. Therefore in such investigations the contralateral muscle is of dubious value as a mean of control. As regards number, distribution and length of muscle spindles there exist only small differences between the various strains of rats.     

Chronic methamphetamine and its withdrawal modify behavioral and neuroendocrine circadian rhythms

Chronic methamphetamine (MA) administration via the drinking water not only induced hyperactivity, but phase delayed the rat rest-activity cycle under entrained conditions. The minimum and/or maximum of the rhythms in eating, drinking, body weight, core body temperature and plasma/urine corticosterone were delayed. The different phase shifts of peak and trough values can also be a result of modulation in the wave form of the rhythms. The fall, but not the rise, of nocturnal pineal melatonin secretion occurred 4 hours earlier in MA-treated rats than in controls: this pattern was still present 1 week after withdrawal, but no longer after 4 weeks withdrawal. Neither chronic MA nor its withdrawal had any effect on plasma thyrotropin. These patterns after chronic MA intake fall into two groups: those rhythms whose peak and/or trough are delayed and those that are not. We thus interpret chronic MA application as modulating the eating rhythm (though not directly through rhythmic MA levels in the CNS), and that this in turn changes all food-dependent rhythms. In contrast, the circadian rhythms of melatonin and thyrotropin remain independent.     

Green light attenuates melatonin output and sleepiness during sleep deprivation

Melatonin output covaries with sleepiness, with both peaking early morning. Bright white light suppresses this output, but it is not known if such treatment ameliorates nighttime sleepiness during sleep deprivation. However, sleep-deprived subjects find such light irritating. Humans are particularly sensitive to green light, and melatonin output is more readily suppressed by this hue. A pilot study using different green light regimens showed that sleep-deprived subjects well tolerated 2,000 lux green light given 10 min hourly, and that this dose reduced nighttime melatonin output. The main study gave this light treatment vs. a low intensity red/green light control, from 1900 hr for 11 hr, to two groups of subjects (n = 6 each) sleep deprived for 36 hr. Urine was collected at 6-hr intervals during sleep loss and on a baseline day. Vigilance performance, subjective sleepiness, and oral temperature were monitored during sleep loss. The experimental condition suppressed urine 6-hydroxymelatonin sulfate (aMT6s) output between 0000 hr and 0600 hr, and increased it 0600-1200 hr; but there was no change in total 24-hr values. The control condition had no such effects. The oral temperature rhythm remained unchanged. Vigilance and subjective sleepiness were improved significantly relative to control values during 0000-0600 hr; these improvements were maintained somewhat over the 0600-1200-hr period, contrary to what one might expect if the delayed melatonin surge at this time was increasing sleepiness. Although the bright green light helped counteract sleepiness, any causal link with changes in melatonin output seem tenuous.     

Immunopathologic Role of Proteoglycan Antigens in Rheumatoid Joint Disease

Cell-mediated immunity to proteoglycan antigens was assessed by leucocyte migration inhibition and by lymphocyte stimulation tests in patients with rheumatoid arthritis or with ankylosing spondylarthritis, in patients with relapsing synovitis after a single trauma to their knee joints, and in healthy donors. Both tests revealed a sensitization in most of the patients examined with various proteoglycan antigens derived from human cartilaginous tissues, rheumatoid synovial fluid, and species-common antigen of bovine nasal cartilage. Anybodies against proteoglycan antigens of human articular cartilage were detected by solid-phase radioimmunoassay in eleven out of twenty-nine sera from patients with rheumatoid arthritis and in four out of six rheumatoid synovial fluids. The results suggest that the cartilage antigenic components released by an inflammatory process or trauma may trigger a vicious circle of chronic inflammation and joint destruction.     

Correlations of Monocyte Phagocytic Receptor Expressions with Serum Immune Complex Level in Systemic Lupus Erythematosus

The expression of FcγRI, FcγRII, and FcγRIII (the IgG receptors CD64, CD32, CD16) as well as CR3 (the C3bi receptor, CD11b) on monocytes in the blood of patients with systemic lupus erythematosus (SLE) was investigated. The relationship between the receptor expression and the serum immune complex (IC) concentration was analysed. The decrease in mean fluorescence intensity (FI) of the FcγRII of patients' monocytes stained by specific monoclonal antibodies (MoAb IV3) was very close to statistical significance ( P = 0.052). The expression (FI) of CR3 (using MoAb OKM1) on monocytes of patients was also decreased, but not significantly. The detected decrease of FcγRII and CR3 was inversely correlated with the high circulating immune complex level in patients' sera. At the same time, FcγRI expression on SLE monocytes (using MoAb 32) was significantly elevated and this change was in parallel with the serum IC concentration.