Targeting glia cells: novel perspectives for the treatment of neuropsychiatric diseases.

Neuropsychiatric disorders are devastating mental illnesses with a high economic burden. The additional morbidity associated with social issues that arises along with the course of these diseases increases the need for a clear understanding of their etiopathogenesis to allow an implementation of novel pharmacological strategies. Yet a poor knowledge about interactions occurring at the glia-neuron interface in health and disease still hampers innovative discoveries, despite the fact that glia cells have been long described to actively participate in the regulation of brain circuits. The purpose of this review was to collect the scattered literature on the involvement of glia cells in neuropsychiatric disorders and to describe how also these cells besides neurons might be responsive to current pharmacological interventions. We hope thereby to offer alternative approaches for investigations that may open avenues to search for new potential targets for drug discovery.

Lack of interaction of endocannabinoids and 5-HT(3) neurotransmission in associative fear circuits of the amygdala: evidence from electrophysiological and behavioural experiments.

Both the serotonergic and the endocannabinoid system play a major role in mediating fear and anxiety. In the basolateral amygdala (BLA) it has been shown that the cannabinoid receptor 1 (CB1) is highly co-expressed with 5-HT3 receptors on GABAergic interneurons suggesting that 5-HT3 receptor activity modulates CB1-mediated effects on inhibitory synaptic transmission. In the present study, we investigated the possible interactions of CB1 and 5-HT3-mediated neuronal processes in the BLA using electrophysiological and behavioural approaches. Whole-cell patch-clamp recordings were performed in coronal brain slices of mice. Electric stimuli were delivered to the lateral amygdala to evoke GABAA receptor-mediated inhibitory postsynaptic currents (GABAA-eIPSCs) in the BLA. The induction of LTDi, a CB1-mediated depression of inhibitory synaptic transmission, was neither affected by the 5-HT3 antagonists ondansetron (OND; 20 µM) and tropisetron (Trop; 50 nM) nor by the 5-HT3 agonists SR57227A (10 µM). In auditory fear conditioning tests, mice treated with SR57227A (3.0mg/kg i.p.) showed sustained freezing, whereas treatment with Trop (1.0 mg/kg i.p.) decreased the expression of conditioned fear. These effects were overruled by the CB1 antagonist rimonabant (RIM; 3.0 mg/kg), which caused increased freezing with or without co-treatment with Trop. In summary, these experiments do not support a functional interaction between CB1 and 5-HT3 receptors at the level of GABA neurotransmission in the BLA nor in terms of fear regulation.

Acute antidepressant treatment differently modulates ERK/MAPK activation in neurons and astrocytes of the adult mouse prefrontal cortex.

The onset of action of antidepressants (ADs) usually takes several weeks, but first molecular responses to these drugs may appear already after acute administration. The Extracellular Signal-regulated Kinase/Mitogen-Activated Protein Kinase (ERK/MAPK) signaling pathway is a target of ADs and an important pathway involved in cellular plasticity. In major depressive disorder (MDD), especially the prefrontal cortex (PFC) and hippocampus (Hip) are most likely affected in depressive patients and recent work revealed a hyperactivated ERK signaling in the rat PFC after chronic stress, a precipitating factor for MDD. Strong evidences support that not only neurons but also astrocytes participate in neuronal activity and may therefore additionally be a substrate of AD action. In this study, we show by Western blot that neither fluoxetine (FLX) nor desipramine (DMI) preferentially affects the activation of one of the two ERK isoforms, ERK1 and ERK2, with respect to the other. Further immunohistochemical analysis in the PFC revealed that basal levels of phospho-activated ERK (pERK) are mostly found in neurons in contrast to very few astrocytes. Both ADs can inhibit neuronal pERK as early as 15 min after drug administration with peculiar regional and layer specificities. Contrarily, at this time point none of the two ADs shows a clear modulation of astrocytic pERK. We propose that this mechanism of action of ADs may be protective against an exacerbated cortical ERK activity that may exert detrimental effects on susceptible neuronal populations. Our findings on acute effects of AD treatment in the adult mouse PFC encourage to examine further how this treatment might influence pERK in animal models of depression to identify early targets of AD action.

Quality of life, body image, and psychiatric complications in patients with a burn trauma: preliminary study of the italian version of the burn specific health scale-brief.

Burn patients may suffer both physical and psychopathological consequences and their quality of life and the presence of psychopathological symptoms should be evaluated. The Burn Specific Health Scale - Brief (BHSH-B) is a tried and tested instrument for assessing burn patients' quality of life. The aim of this study is to propose the Italian translation of BSHS-B and presents the preliminary results of an exploratory study. The Italian version of the BSHS-B was administered to a sample group of 50 burn victims. Reliability was verified by Cronbach's alpha, and construct validity was evaluated through correlation with the Short Form 36 Health Survey Questionnaire (SF-36) and the Self-report Symptom Inventory - Revised (SCL-90). The entire scale and two out of three domains showed Cronbach's alpha values higher than 0.8. Significant correlations were identified between BSHS-B subscales and the SF-36 subscales Physical Pain and Social Activities. Several psychopathological SCL-90 subscales correlated with BSHS-B subscales Heat Sensitivity and Body Image. It was concluded that our translation of BSHS-B was reliable and showed good construct validity. The drawbacks of this study are the limited size of the sample and the wide variety of types of burn injuries.

Long-term follow-up of open commissurotomy versus bileaflet valve replacement for rheumatic mitral stenosis.

OBJECTIVE: Despite the achievements of third generation mechanical cardiac valve prostheses, conservative procedures are still considered the best surgical option for rheumatic mitral valve stenosis. To compare long-term results of open mitral commissurotomy (Group A) and mitral valve replacement with bileaflet prostheses (Group B) a 15-year follow-up study was carried out. METHODS: From January 1981 to May 1996, 540 consecutive patients with pure isolated rheumatic mitral stenosis underwent mitral valve surgery: 300 had mitral commissurotomy and 240 valve replacement. The follow-up was 99.05% complete and ranged between 1 and 185 months in Group A and from 1 to 171 months in Group B. RESULTS: Hospital mortality was 2% in Group A and 2.08% in Group B. Late mortality was 1% in Group A and 3% in Group B. The 10-year survival rates were 98.7% +/- 1% in Group A and 93.7% +/- 3% in Group B. There was a statistically significant difference of freedom from reoperation in Group B (97.7% +/- 1%) versus Group A (88.1% +/- 2%) (P = 0.04). In group A 14 embolic events occurred (93.7% +/- 2%), and 15 (6.52%) in Group B (83.9% +/- 7%). Haemorrhagic events were observed in 2 patients (0.68%) of Group A (99.3% +/- 0.5%) and in 3 patients (1.3%) of Group B (98.4% +/- 1%). CONCLUSIONS: Long term results of mitral commissurotomy were more satisfactory than those obtained with bileaflet valves. Reoperation rate was higher in mitral commissurotomy.