Activity-dependent switch of GABAergic inhibition into glutamatergic excitation in astrocyte-neuron networks.

Interneurons are critical for proper neural network function and can activate Ca2+ signaling in astrocytes. However, the impact of the interneuron-astrocyte signaling into neuronal network operation remains unknown. Using the simplest hippocampal Astrocyte-Neuron network, i.e., GABAergic interneuron, pyramidal neuron, single CA3-CA1 glutamatergic synapse, and astrocytes, we found that interneuron-astrocyte signaling dynamically affected excitatory neurotransmission in an activity- and time-dependent manner, and determined the sign (inhibition vs potentiation) of the GABA-mediated effects. While synaptic inhibition was mediated by GABAA receptors, potentiation involved astrocyte GABAB receptors, astrocytic glutamate release, and presynaptic metabotropic glutamate receptors. Using conditional astrocyte-specific GABAB receptor (Gabbr1) knockout mice, we confirmed the glial source of the interneuron-induced potentiation, and demonstrated the involvement of astrocytes in hippocampal theta and gamma oscillations in vivo. Therefore, astrocytes decode interneuron activity and transform inhibitory into excitatory signals, contributing to the emergence of novel network properties resulting from the interneuron-astrocyte interplay.

Modulation of osteoblast activity by serum from diabetic and non-diabetic patients on hemodialysis: a three-dimensional culture study.

BACKGROUND: The aims of our study were to develop a three-dimensional model based on normal human osteoblasts and to determine, with this method, the osteoblastic response to sera of non-diabetic and diabetic patients on hemodialysis for chronic renal failure. METHODS: A protocol for culture of osteoblastic cells in three-dimensional meshworks of bovine type I collagen was developed. The effect on cultures of sera from three groups of patients was studied: 1) 12 diabetic patients on hemodialysis [age: 65 +/- 5.2 years; sex: 6 men, 6 women; duration of dialysis treatment: 21.25 (641) months]; 2) 12 non-diabetic patients on hemodialysis [age: 65.5 +/- 5.4 years; sex: 6 men, 6 women; duration of dialysis treatment: 21.35 (6-40) months]; and 3) 12 healthy volunteer donors (age: 64.2 +/- 4.9 years; 6 men, 6 women). The three-dimensional cultures obtained were processed in the same way as undecalcified bone biopsies, sectioned and stained. A histomorphometrical study was conducted. Parameters calculated were cell number, volume of newly-formed collagen, volume of newly-formed collagen per cell, mineral volume and mineral volume per cell. RESULTS: Number of osteoblastic cells was significantly higher in non-diabetic than in diabetic and control serum-treated cultures. Newly-formed collagen volume was significantly higher in non-diabetic serum-treated cultures than in controls. Deposited mineral volume was significantly lower in diabetic and non-diabetic serum-treated cultures compared to control serum-treated cultures. CONCLUSIONS: The model of three-dimensional culture proposed in the present study is useful in the study of different osteoblast functions including the rate of collagen formation and mineralization.

Astrocytes in endocannabinoid signalling.

Astrocytes are emerging as integral functional components of synapses, responding to synaptically released neurotransmitters and regulating synaptic transmission and plasticity. Thus, they functionally interact with neurons establishing tripartite synapses: a functional concept that refers to the existence of communication between astrocytes and neurons and its crucial role in synaptic function. Here, we discuss recent evidence showing that astrocytes are involved in the endocannabinoid (ECB) system, responding to exogenous cannabinoids as well as ECBs through activation of type 1 cannabinoid receptors, which increase intracellular calcium and stimulate the release of glutamate that modulates synaptic transmission and plasticity. We also discuss the consequences of ECB signalling in tripartite synapses on the astrocyte-mediated regulation of synaptic function, which reveal novel properties of synaptic regulation by ECBs, such as the spatially controlled dual effect on synaptic strength and the lateral potentiation of synaptic efficacy. Finally, we discuss the potential implications of ECB signalling for astrocytes in brain pathology and animal behaviour.

[Initial treatment trends in patient with osteoporosis: use of antiresorptive agents and pharmacologic supplements (calcium and vitamin D) in clinical practice]. / Pauta de tratamiento inicial en pacientes con osteoporosis: uso de antirresortivos y suplementos farmacológicos (calcio y vitamina D) en la práctica clínica.

OBJECTIVE: To describe the percentage of prescription of pharmacologic supplements in patients starting antiresorptive treatment (ART) for osteoporosis by specialists. DESIGN: Cross-sectional, naturalistic, multicenter study with retrospective data collection. PATIENTS AND METHODS: 88 Spanish primary care (PC) physicians participated as well as those from Bone Metabolism Unit / Rheumatology and Gynecology units. Patients were females with osteoporosis who started ART in the 12 to 36 months prior to the visit. MAIN OUTCOMES: General clinical variables and those related to osteoporosis treatment (both ART and pharmacologic supplements) and an opinion survey on pharmacologic supplements. RESULTS: 480 patients were included. Mean age (SD) was 65.8 (9.2) years. Pharmacologic supplements were prescribed in 69.6% of patients and were more frequent in patients treated in Bone Metabolism/Rheumatology Units (89.1%) than patients treated by PC (60.3%) and Gynecology (55.6%). In the physician survey, 72% of the Bone Metabolism / Rheumatology Unit physicians responded that the Vitamin D supplements were necessary for treatment of osteoporosis vs. 38.5% of PC physicians (p=0.058). CONCLUSIONS: The use of pharmacologic supplements in the onset of treatment with ART represents more than 60% of the sample, although differences were seen between specialists, with a greater percentage of patients with supplements in the Bone Metabolism/Rheumatology Units than in PC and Gynecology, despite guidelines primarily recommend the use of pharmacologic supplements in these patients.

Observational study of treatment compliance in women initiating antiresorptive therapy with or without calcium and vitamin D supplements in Spain.

OBJECTIVE: The aims of this study were to evaluate the compliance with antiresorptive therapy (ART) and supplements in Spain and to analyze the validity of the different treatment compliance assessment methods. METHODS: A cross-sectional study with retrospective data collection was carried out in women starting ART, evaluating indirect objective compliance, self-reported compliance, and the Morisky-Green questionnaire. RESULTS: A total of 480 women with a mean (SD) age of 65.8 (9.2) years were studied. Of these women, 62.9% received calcium and/or vitamin D supplements in addition to ART. According to the objective compliance method, 76.9% of the women were compliers (≥80%) with bisphosphonates; 69.4%, with selective estrogen receptor modulators; and 61.8%, with supplements (P < 0.01). Using the self-reported compliance, we identified 91% compliers with antiresorptive drugs and 75% with supplements. Using the Morisky-Green test, we classified 60.8% of the women as compliers with antiresorptive drugs and 48.4% with supplements. Combining the objective and self-reported compliance, 29.5% of the women did not adequately comply with ART and 56% with the drug supplements. CONCLUSIONS: With all three compliance measures, supplements were the treatment yielding the lowest percentage of compliers. Bisphosphonates constituted the treatment offering the best objective compliance: 38.2% of the women with drug supplements and between 23.1% and 30.6% of the women with ART failed to exceed the theoretical value of 80% regarded as representing good compliance.