Stereometric characteristics of ultrastructure of presynaptic terminals in the dorsal horn of the cat spinal cord

Morphometric statistical techniques were used to investigate geometric aspects of 240 axodendritic presynaptic terminals (PT) located in the dorsal horn of the gray matter of the cat spinal cord. Parameters describing the configuration and average spatial radius of the three-dimensional PT (approximated by irregular ellipsoid were estimated on the basis of the morphometry of random PT sections applying aspects of the theory of probability. Lack of any correlation between location of the active zone and the configurational pattern (extent) of terminals was demonstrated. Densitometric distribution of average spatial PT radii was obtained (mean: 0.820 µm). The relatively limited scatter of this distribution would indicate extremely close similarity between parameters of the PT comprising the test group.Dnepropetrovsk University. A. A. Bogomolets Institute of Physiology, Academy of the Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 3, pp. 403–410, May–June, 1989.     

A conceptual mathematical model of the aquatic communities of lakes Naroch and Myastro (Belarus)

A conceptual mathematical model of the dynamics of fish and zooplankton (rotifer) populations of connected lakes Naroch and Myastro (Belarus) is built and examined with parameters based on field data. It is shown that community coupling and trophic interactions give rise to both regular and irregular oscillations in population numbers.     

Analysis of acute and chronic effects of antidepressive agents in a learned helplessness model in mice

In experimental learned helplessness in mice determined by preliminary inavoidable aversive exposure, activity of tricyclic antidepressants (desipramine, chlorimipramine, amitryptyline), type A MAO inhibitors (pyrazidol), and atypical (zimelidine, trazodon, befuralin) antidepressants as well as that of potential antidepressants (LIS-30, DZK-153) were determined upon chronic administration. The tricyclic compounds, befuralin and DZK-153 removed learned helplessness only after 14 days of administration. The substances with a predominant serotoninomimetic action (zimelidin, trazodon in high doses, pyrazidol, LIS-30) showed high efficacy following 6 days of administration. Single administration of the substances under study did not make it possible to disclose their specific antidepressant activity.     

Remission in psoriatic arthritis: is it possible and how can it be predicted?

Introduction

Since remission is now possible in psoriatic arthritis (PsA) we wished to examine remission rates in PsA patients following anti tumour necrosis factor alpha (TNFα) therapy and to examine possible predictors of response.

Methods

Analysis of a prospective patient cohort attending a biologic clinic, between November 2004 and March 2008, was performed prior to commencing therapy and at regular intervals. Baseline clinical characteristics including demographics, previous disease-modifying antirheumatic drug (DMARD) response, tender and swollen joint counts, early morning stiffness, pain visual analogue score, patient global assessment, C reactive protein (CRP) and health assessment questionnaire (HAQ) were collected.

Results

A total of 473 patients (152 PsA; 321 rheumatoid arthritis (RA)) were analyzed. At 12 months remission, defined according to the disease activity score using 28 joint count and CRP (DAS28-CRP), was achieved in 58% of PsA patients compared to 44% of RA patients, significant improvement in outcome measures were noted in both groups (P < 0.05). Analysis of a subgroup of PsA and RA patients matched for DAS28-CRP at baseline also showed higher numbers of PsA patients achieving remission. Linear regression analysis identified the HAQ at baseline as the best predictor of remission in PsA patients (P < 0.001).

Conclusions

DAS28 remission is possible in PsA patients at one year following anti-TNF therapy, at higher rates than in RA patients and is predicted by baseline HAQ.     

CaMKII translocation requires local NMDA receptor-mediated Ca2+ signaling

Excitatory synaptic transmission and plasticity are critically modulated by N-methyl-D-aspartate receptors (NMDARs). Activation of NMDARs elevates intracellular Ca(2+) affecting several downstream signaling pathways that involve Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Importantly, NMDAR activation triggers CaMKII translocation to synaptic sites. NMDAR activation failed to induce Ca(2+) responses in hippocampal neurons lacking the mandatory NMDAR subunit NR1, and no EGFP-CaMKIIalpha translocation was observed. In cells solely expressing Ca(2+)-impermeable NMDARs containing NR1(N598R)-mutant subunits, prolonged NMDA application elevated internal Ca(2+) to the same degree as in wild-type controls, yet failed to translocate CaMKIIalpha. Brief local NMDA application evoked smaller Ca(2+) transients in dendritic spines of mutant compared to wild-type cells. CaMKIIalpha mutants that increase binding to synaptic sites, namely CaMKII-T286D and CaMKII-TT305/306VA, rescued the translocation in NR1(N598R) cells in a glutamate receptor-subtype-specific manner. We conclude that CaMKII translocation requires Ca(2+) entry directly through NMDARs, rather than other Ca(2+) sources activated by NMDARs. Together with the requirement for activated, possibly ligand-bound, NMDARs as CaMKII binding partners, this suggests that synaptic CaMKII accumulation is an input-specific signaling event.     

Matrix metalloproteinase-7 disrupts dendritic spines in hippocampal neurons through NMDA receptor activation

Dendritic spines are protrusions from the dendritic shaft that host most excitatory synapses in the brain. Although they first emerge during neuronal maturation, dendritic spines remain plastic through adulthood, and recent advances in the molecular mechanisms governing spine morphology have shown them to be exquisitely sensitive to changes in the micro-environment. Among the many factors affecting spine morphology are components and regulators of the extracellular matrix (ECM). Modification of the ECM is critical to the repair of injuries throughout the body, including the CNS. Matrix metalloproteinase (MMP)-7/matrilysin is a key regulator of the ECM during pathogen infection, after nerve crush and in encephalitogenic disorders. We have investigated the effects of MMP-7 on dendritic spines in hippocampal neuron cultures and found that it induces the transformation of mature, short mushroom-shaped spines into long, thin filopodia reminiscent of immature spines. These changes were accompanied by a dramatic redistribution of F-actin from spine heads into thick, rope-like structures in the dendritic shaft. Strikingly, MMP-7 effects on dendritic spines were similar to those of NMDA treatment, and both could be blocked by channel-specific antagonists. These findings are the first direct evidence that MMPs can influence the morphology of mature dendritic spines, and hence synaptic stability.