BackgroundWe previously showed that beta-amyloid (Aβ), a peptide considered as relevant to Alzheimer's Disease, is able to act as a neuromodulator affecting neurotransmitter release in absence of evident sign of neurotoxicity in two different rat brain areas. In this paper we focused on the hippocampus, a brain area which is sensitive to Alzheimer's Disease pathology, evaluating the effect of Aβ (at different concentrations) on the neurotransmitter release stimulated by the activation of pre-synaptic cholinergic nicotinic receptors (nAChRs, α4β2 and α7 subtypes). Particularly, we focused on some neurotransmitters that are usually involved in learning and memory: glutamate, aspartate and GABA.Methodology/FindingsWe used a dual approach: in vivo experiments (microdialysis technique on freely moving rats) in parallel to in vitro experiments (isolated nerve endings derived from rat hippocampus). Both in vivo and in vitro the administration of nicotine stimulated an overflow of aspartate, glutamate and GABA. This effect was greatly inhibited by the highest concentrations of Aβ considered (10 µM in vivo and 100 nM in vitro). In vivo administration of 100 nM Aβ (the lowest concentration considered) potentiated the GABA overflow evoked by nicotine. All these effects were specific for Aβ and for nicotinic secretory stimuli. The in vitro administration of either choline or 5-Iodo-A-85380 dihydrochloride (α7 and α4β2 nAChRs selective agonists, respectively) elicited the hippocampal release of aspartate, glutamate, and GABA. High Aβ concentrations (100 nM) inhibited the overflow of all three neurotransmitters evoked by both choline and 5-Iodo-A-85380 dihydrochloride. On the contrary, low Aβ concentrations (1 nM and 100 pM) selectively acted on α7 subtypes potentiating the choline-induced release of both aspartate and glutamate, but not the one of GABA.Conclusions/SignificanceThe results reinforce the concept that Aβ has relevant neuromodulatory effects, which may span from facilitation to inhibition of stimulated release depending upon the concentration used.

Neural factors appear to play a major role in the pathogenesis of vitiligo. To investigate the possible correlation between vitiligo and peripheral monoaminergic system activity, we used high-pressure liquid chromatography and electrochemical detector methods to evaluate the basal urine excretion values of catecholamines [norepinephrine (NE), epinephrine and dopamine (DA)], their relative metabolites [3-methoxy-4-hydroxyphenylglycol (MHPG), normetanephrine (NMN), metanephrine (MN), vanilmandelic acid (VMA) and homovanillic acid], as well as 5-hydroxyindoleacetic acid (5-HIAA), in 35 healthy subjects and in 70 patients, suffering from non-segmental vitiligo at different stages of the disease. Levels of NE, DA, NMN, MN, MHPG, VMA and 5-HIAA were found to be significantly higher in patients than in controls. The patients with progressive vitiligo (n = 56) presented increased urinary excretion values for all parameters (in particular, NE levels) than other patients. Interestingly, in patients at its more recent vitiligo onset (<1 yr), NE values were different to those of subjects affected from 1 to 5 yr and from 6 to 10 yr. This result was confirmed by the significant negative relationship detected between NE excretion values and disease duration. In both vitiligo and control groups, significant correlations were found between monoamines as well as between these monoamines and their metabolites. The increase in catecholamine turnover, mainly occurring at the onset of the disease, is probably due to the stress associated with the appearance of lesions. Moreover, considering that these compounds readily produce toxic free-radicals and that vitiliginous subjects have a defective free radical defence mechanism, they may also contribute to the disappearance of melanocytes in the early phases of vitiligo.

Day hospital (DH) treatments for eating disorders (EDs) provide intensive daily care and allow patients to maintain and test their social relations and coping skills at home and outside. Although widespread, their description is lacking. This review compares the different types of DH described in the literature and presents our DH experience in Turin, Italy. We searched Psychinfo and Pubmed with the following keywords: anorexia nervosa, bulimia nervosa, EDs, DH, day treatment and partial hospitalisation. We found and reviewed the DH programmes of eleven specialised centres, which have some shared features but also many differences, suggesting that DH treatments are still largely experimental. Briefly, the shared elements are: biopsychosocial model as reference frame; cognitive-behavioural model or techniques; behavioural contract; patients' selection; body image therapy; involvement of family; weight normalisation/weight gain and modification/normalisation of eating behaviour as objectives. Nonetheless, shared opinions concerning inclusion criteria are lacking; the duration of DH treatment is surprisingly different among centres (from 3 to 39 weeks); the approach to eating and compensation behaviours ranges from control to autonomy; followup and psychometric assessment can be either performed or not; psychological and behavioural objectives can be different. This review suggests the existence of two different DH models: the first has a shorter duration and is mainly symptom-focused; the second is more individual-focused, has a longer duration and is focused on patients' relational skills, psychodynamic understanding of symptoms and more gradual changes in body weight. Further investigation is required to make DH treatment programmes measurable and comparable.

The clinical presentation of Alzheimer's disease is characterized by memory deficits but it also involves the impairment of several cognitive functions. Some of these cognitive and executive functions are mediated by limbic areas and are regulated by dopaminergic neurotransmission. Furthermore, literature data suggest that b-amyloid (Ab) can influence synaptic activity in absence of neurotoxicity and in particular can impair cholinergic modulation of other neurotransmitter actions. In the present study, we evaluated whether small concentrations of Ab could disrupt cholinergic control of dopamine (DA) release in nucleus accumbens using in vivo (brain dialysis) and in vitro (isolated synaptosomes) models. The cholinergic agonist carbachol (CCh) greatly enhanced DA release from dopaminergic nerve endings in nucleus accumbens both in vivo and in vitro. This effect was mainly exerted on muscarinic receptors because it was inhibited by the muscarinic antagonist atropine and it was unaffected by the nicotinic antagonist mecamylamine. Also the nicotinic agonists epibatidine and nicotine evoked a dopaminergic outflow in nucleus accumbens, which, however, was lower. Ab 1-40 in absence of neurotoxicity fully inhibited the DA release evoked by CCh and only marginally affected the DA release evoked by epibatidine. The PKC inhibitor GF109203X mimicked the effect of Ab on DA release and, in turn, Ab impaired PKC activation by CCh. We can suggest that, in nucleus accumbens, Ab disrupted in vivo and in vitro cholinergic control of DA release by acting on muscarinic transduction machinery.

The amyloid cascade hypothesis sustains that beta-amyloid (Abeta) is the main pathogenetic factor of Alzheimer's Disease (AD). Although the direct and indirect neurotoxic role of Abeta are unchallenged, recent findings suggest that the peptide may have so far unforeseen physiological roles. In this regard, the observations showing the ability of Abeta to exert synaptic activities in absence of neurotoxicity are very intriguing. In particular, the peptide is able to affect synaptic transmission of different neurotransmitter systems in key brain areas that regulate executive and cognitive functions, an observation that points Abeta as a new neuromodulator. However, in a pathological context, Abeta may drive functional alterations of several neurotransmitter systems in the early phases of the disease, in turn producing subtle cognitive and behavioural disturbances in addition and before the well known neurodegenerative events. On the other hand, advancing age is the most significant risk factor for the development of AD. In fact, during aging increased Abeta levels have been reported. Moreover, several neurotransmitter systems undergo age-related changes in parallel to a decline of cognitive functions. However, the putative neuromodulatory role of Abeta in the context of aging is nowadays unknown. For these reasons, future studies about the spectrum of action of Abeta (brain areas and neurotransmitter systems affected) are particularly interesting since may suggest new therapeutic targets in order to sustain those functions which may be altered during aging.