CCK-immunoreactive terminals form different types of synapses in the rat and monkey hippocampus

Electronmicroscopic immunocytochemical analysis of the types and patterns of synaptic contacts formed by cholecystokinin (CCK)-containing terminals in the CA1 and CA3 region of the rat and monkey hippocampus reveals numerous symmetric synaptic contacts on cell bodies and dendritic shafts of pyramidal cells in both species. In the monkey, however, CCK-immunoreactive terminals also form asymmetric synaptic contacts with dendritic spines, such contacts are absent or very rare in the rat hippocampus. The present finding in primate hippocampus provides evidence that the same neuropeptides can be found in both symmetric and asymmetric contacts and may be added to other evidence challenging the traditional concept that symmetric synapses mediate exclusively inhibitory and asymmetric exclusively excitatory transmission. Furthermore, although our comparative analysis confirms considerable similarities in the distribution of CCK-containing elements in primate and rodent hippocampus it also revealed a potentially important difference in synaptoarchitecture that should be taken into account in extrapolations from one species to the other.     

Catecholamine-containing neurons in the peripheral nervous system of Aplysia

Numerous green-fluorescent neurons have been revealed by means of the glyoxylic acid histochemical method in cryostat sections of several organs of two Adriatic aplysiid gastropods, Aplysia depilans and A. fasciata. Catecholamine-containing perikarya and their processes have been found to be especially abundant in the vaginal portion of the large hermaphrodite duct, in the penis and its sheath, and in the gill. In the reproductive organs, two subpopulations of catecholamine-containing neurons could be distinguished according to their size and location. Axons of larger neurons formed bundles which seemed to project at the CNS.     

Transneuronal degeneration in the Rolando substance of the primate spinal cord evoked by axotomy-induced transganglionic degenerative atrophy of central primary sensory terminals

Summary Transection of the sciatic nerve in Rhesus monkeys and the consequent transganglionic degenerative atrophy (TDA) of central terminals of primary afferents result in transneuronal degeneration of substantia gelatinosa (SG) cells. Severe degeneration is characterized by an increased electron density of the nucleus and by conspicuous shrinkage of the cytoplasm, mitochondrial swelling, dilation of cisterns of the rough-surfaced endoplasmic reticulum, accumulation of free ribosomes and an electron-dense material in the cytoplasm. In the mild form, dilation of cisternal elements of the endoplasmic reticulum, swollen mitochondria and accumulation of free ribosomes takes place. About 10% of SG cells in segment L₅ undergo the severe form whereas the rest shows signs of the mild form. Cytoplasmic alterations that occur during transneuronal degeneration seem to start at the level of subsurface cisterns. Dendrites and axons of transneuronally degenerating SG cells also show a conspicuous electron density. By analyzing the synaptic relationships of such darkened dendrites, connections in the upper dorsal horn can be deciphered. Modular units of the primary nociceptive analyzer that evaluate noxious and innocuous inputs on the basis of thin versus thick (AC/A) afferent activity and subjecting them to descending control appear to be recruited from structurally dispersed elements of synaptic glomeruli. These are arranged alongside dendritic processes of large antenna cells which relay impulses to projection cells of the spinothalamic tract.     

Differential response of cycling and noncycling cells to inducers of DNA synthesis and mitosis

The objective of this study was to determine whether cells in G(0) phase are functionally distinct from those in G(1) with regard to their ability to respond to the inducers of DNA synthesis and to retard the cell cycle traverse of the G(2) component after fusion. Synchronized populations of HeLa cells in G(1) and human diploid fibroblasts in G(1) and G(0) phases were separately fused using UV-inactivated Sendai virus with HeLa cells prelabeled with [(3)H]ThdR and synchronized in S or G(2) phases. The kinetics of initiation of DNA synthesis in the nuclei of G(0) and G(1) cells residing in G(0)/S and G(1)/S dikaryons, respectively, were studied as a function of time after fusion. In the G(0)/G(2) and G(1)/G(2) fusions, the rate of entry into mitosis of the heterophasic binucleate cells was monitored in the presence of Colcemid. The effects of protein synthesis inhibition in the G(1) cells, and the UV irradiation of G(0) cells before fusion, on the rate of entry of the G(2) component into mitosis were also studied. The results of this study indicate that DNA synthesis can be induced in G(0)nuclei after fusion between G(0)- and S-phase cells, but G(0) nuclei are much slower than G(1) nuclei in responding to the inducers of DNA synthesis because the chromatin of G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells is more condensed than it is in G(1) cells. A more interesting observation resulting from this study is that G(0) cells differ from G(1) cells with regard to their effects on the cell cycle progression of the G(2) nucleus into mitosis. This difference between G(0) and G(1) cells appears to depend on certain factors, probably nonhistone proteins, present in G(1) cells but absent in G(0) cells. These factors can be induced in G(0) cells by UV irradiation and inhibited in G(1) cells by cycloheximide treatment.     

Exercise training in childhood-onset systemic lupus erythematosus: a controlled randomized trial

Introduction

Exercise training has emerged as a promising therapeutic strategy to counteract physical dysfunction in adult systemic lupus erythematosus. However, no longitudinal studies have evaluated the effects of an exercise training program in childhood-onset systemic lupus erythematosus (C-SLE) patients. The objective was to evaluate the safety and the efficacy of a supervised aerobic training program in improving the cardiorespiratory capacity in C-SLE patients.

Methods

Nineteen physically inactive C-SLE patients were randomly assigned into two groups: trained (TR, n = 10, supervised moderate-intensity aerobic exercise program) and non-trained (NT, n = 9). Gender-, body mass index (BMI)- and age-matched healthy children were recruited as controls (C, n = 10) for baseline (PRE) measurements only. C-SLE patients were assessed at PRE and after 12 weeks of training (POST). Main measurements included exercise tolerance and cardiorespiratory measurements in response to a maximal exercise (that is, peak VO₂, chronotropic reserve (CR), and the heart rate recovery (ΔHRR) (that is, the difference between HR at peak exercise and at both the first (ΔHRR1) and second (ΔHRR2) minutes of recovery after exercise).

Results

The C-SLE NT patients did not present changes in any of the cardiorespiratory parameters at POST (P > 0.05). In contrast, the exercise training program was effective in promoting significant increases in time-to-exhaustion (P = 0.01; ES = 1.07), peak speed (P = 0.01; ES = 1.08), peak VO₂ (P = 0.04; ES = 0.86), CR (P = 0.06; ES = 0.83), and in ΔHRR1 and ΔHRR2 (P = 0.003; ES = 1.29 and P = 0.0008; ES = 1.36, respectively) in the C-SLE TR when compared with the NT group. Moreover, cardiorespiratory parameters were comparable between C-SLE TR patients and C subjects after the exercise training intervention, as evidenced by the ANOVA analysis (P > 0.05, TR vs. C). SLEDAI-2K scores remained stable throughout the study.

Conclusion

A 3-month aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in C-SLE patients.

Trial registration

NCT01515163.     

Distinct functions of alpha3 and alpha(v) integrin receptors in neuronal migration and laminar organization of the cerebral cortex

Changes in specific cell-cell recognition and adhesion interactions between neurons and radial glial cells regulate neuronal migration as well as the establishment of distinct layers in the developing cerebral cortex. Here, we show that alpha3beta1 integrin is necessary for neuron-glial recognition during neuronal migration and that alpha(v) integrins provide optimal levels of the basic neuron-glial adhesion needed to maintain neuronal migration on radial glial fibers. A gliophilic-to-neurophilic switch in the adhesive preference of developing cortical neurons occurs following the loss of alpha3beta1 integrin function. Furthermore, the targeted mutation of the alpha3 integrin gene results in abnormal layering of the cerebral cortex. These results suggest that alpha3beta1 and alpha(v) integrins regulate distinct aspects of neuronal migration and neuron-glial interactions during corticogenesis.     

DNA damage-induced neural precursor cell apoptosis requires p53 and caspase 9 but neither Bax nor caspase 3

Programmed cell death (apoptosis) is critical for normal brain morphogenesis and may be triggered by neurotrophic factor deprivation or irreparable DNA damage. Members of the Bcl2 and caspase families regulate neuronal responsiveness to trophic factor withdrawal; however, their involvement in DNA damage-induced neuronal apoptosis is less clear. To define the molecular pathway regulating DNA damage-induced neural precursor cell apoptosis, we have examined the effects of drug and gamma-irradiation-induced DNA damage on telencephalic neural precursor cells derived from wild-type embryos and mice with targeted disruptions of apoptosis-associated genes. We found that DNA damage-induced neural precursor cell apoptosis, both in vitro and in vivo, was critically dependent on p53 and caspase 9, but neither Bax nor caspase 3 expression. Neural precursor cell apoptosis was also unaffected by targeted disruptions of Bclx and Bcl2, and unlike neurotrophic factor-deprivation-induced neuronal apoptosis, was not associated with a detectable loss of cytochrome c from mitochondria. The apoptotic pathway regulating DNA damage-induced neural precursor cell death is different from that required for normal brain morphogenesis, which involves both caspase 9 and caspase 3 but not p53, indicating that additional apoptotic stimuli regulate neural precursor cell numbers during telencephalic development.     

Neurogenesis in adult primate neocortex: an evaluation of the evidence

Reports of continuous genesis and turnover of neurons in the adult primate association neocortex--the site of the highest cognitive functions--have generated great excitement. Here, I review the available evidence, and question the scientific basis of this claim.