Neuroscience
-
In the last thirty years, obesity has reached epidemic proportions and is now regarded as a major health issue in contemporary society trending to serious economic and social burdens. The latest projections of the World Health Organization are alarming. By 2030, nearly 60% of the worldwide population could be either obese or overweight, highlighting the needs to find innovative treatments. ⋯ Nevertheless, obesity drug therapy remains quite limited on its effectiveness to actually overcome the obesogenic environment. Thus, innovative unimolecular polypharmacology strategies, able to simultaneously target multiple actors involved in the obesity initiation and expansion, were developed during the last ten years opening a new promising avenue in the pharmacological management of obesity. In this review, we first describe the clinical features of obesity-associated conditions and then focus on the outcomes of currently approved drug therapies for obesity as well as new ones expecting to reach the clinic in the near future.
-
Brain ischaemia, which can cause severe nerve injury, is a global health challenge. Long non-coding RNA (lncRNA) growth-arrest specific 5 (Gas5) has been documented to exert tumour suppressive effects in several cancers. However, its role in cerebrovascular disease still requires further investigation. ⋯ LncRNA Gas5 inhibited miR-21 expression, leading to elevated levels of Pten. In vitro experiments revealed that lncRNA Gas5 depletion and miR-21 elevation resulted in the suppression of neuronal apoptosis, thus promoting neuronal survival via the PI3K/Akt signalling pathway. These findings demonstrate that lncRNA Gas5 increases miR-21 and activates Pten, contributing to the development of ischaemic brain injury, supporting the silencing of lncRNA Gas5 as a possible therapeutic target for the treatment of ischaemic brain injury.
-
Neurophysiological studies suggest that music reading facilitates sensorimotor cortex. The aim of this study was to evaluate (1) whether in pianists, reading notes in bass and treble clef selectively enhances right and left primary motor cortex (M1) excitability; and (2) whether reading notes played with the thumb or little finger selectively modulates the excitability of specific muscles. Twenty musicians (11 pianists, 9 non-pianists) participated. ⋯ Moreover, in the treble clef condition motor evoked potentials (MEPs) induced by TMS of the left M1 were higher when pianists read notes to be played with the 5° finger (little finger) with respect to 1° finger (thumb) notes, whereas in the bass clef condition TMS of the right M1 induced higher MEPs for 1° finger note compared to 5° finger notes. No significant modulation was observed in non-pianists. These data support the view that music reading may induce specific inter- and intra-hemispheric modulation of the motor cortex excitability.
-
Defective proprioceptive integration may play a role in the pathophysiology of motor symptoms in Parkinson's disease (PD). Dysfunction related to proprioceptively-evoked postural reactions in PD patients is still a controversial issue, with only a limited number of studies to date and mostly discordant results. The aims of the present study were (1) to determine whether or not the proprioceptive defect in PD underlies postural impairment and (2) whether or not deep brain stimulation of the subthalamic nucleus (STN-DBS) affects proprioceptive integration. ⋯ We found a significant positive effect of STN-DBS on these postural features. Our findings indicate that Parkinson patients, even in the absence of any clinical evidence of instability, falls, or freezing, use proprioceptive information for postural control less efficiently than healthy subjects. Furthermore, STN-DBS was found to improve proprioceptive integration, with positive impacts on postural orientation and balance.
-
Evidence suggests the hypothalamic-pituitary-adrenal (HPA) axis is involved in Alcohol Use Disorders (AUDs), which might be mediated by an imbalance of glucocorticoid receptor (GR), GRα and GRβ, activity. GRβ antagonizes the GRα isoform to cause glucocorticoid (GC) resistance. In the present study, we aimed to investigate the effects of chronic continuous free-choice access to ethanol on GR isoform expression in subregions of the mesocorticolimbic reward circuit. ⋯ These data indicate that the expression of GRα and GRβ isoforms are differentially affected by ethanol drinking despite HPA-associated peptides remaining unchanged, at least at the time of tissue harvesting. Moreover, the results suggest that GR changes may stem from ethanol-induced GC-resistance in the NAcsh. These findings confirm a role for stress in high ethanol drinking, with GRα and GRβ implicated as targets for the treatment of AUDs.