Neuroscience
-
Loneliness has a strong neurobiological basis reflected by its specific relationships with structural brain connectivity. Critically, affect traits are highly related to loneliness, which shows close association with the onset and severity of major depressive disorder. ⋯ The findings of this study confirmed that both global and average local efficiency negatively mediated the association between low positive affect and high negative affect and loneliness, and the mediation was more sensitive to sibling-shared affect traits. The findings have important implications for interventions targeted at reducing the detrimental impact of familiar negative emotional experiences and loneliness.
-
Soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins mediate membrane fusion events in eukaryotic cells. Traditionally recognized as major players in regulating presynaptic neurotransmitter release, accumulative evidence over recent years has identified several SNARE proteins implicated in important postsynaptic processes such as neurotransmitter receptor trafficking and synaptic plasticity. Here we analyze the emerging data revealing this novel functional dimension for SNAREs with a focus on the molecular specialization of vesicular recycling and fusion in dendrites compared to those at axon terminals and its impact in synaptic transmission and plasticity.
-
Humans are more vulnerable to addiction in comparison to all other mammals, including nonhuman primates, yet there is a lack of research addressing this. This paper reviews the field of comparative addiction neuroscience, highlighting the significant inter-species variation in the mesocortical dopaminergic and other neuromodulatory systems involved in addiction. Artificial selection gives rise to significant changes in neuroanatomy, neurophysiology and behaviour as shown in certain rodent strains and other domesticated animals. ⋯ During the course of human evolution, traits crucial to our survival, expansion and domination (traits such as the ability to innovate, adapt to different environments and thrive in a civilization) have been positively selected for, yet also predispose humans to addiction. This is evident in our unique neurochemistry and receptor-drug activation potencies. Examples of these are provided as possible targets for precision medicine.
-
SNARE-complexes drive the fusion of membrane-bound vesicles with target membranes or with each other (homotypic fusion). The SNARE-proteins are subdivided into Qa, Qb, Qc and R-SNAREs depending on their position in the four-helical SNARE-bundle. Here, we review the SNAP-25 protein sub-family, which includes both the Qb and Qc SNARE-domains within a single protein. ⋯ SNAP-29 is present on intracellular membranes and performs functions in autophagosome-to-lysosome fusion, among others. An overlapping function for SNAP-47 was described; in addition, SNAP-47 mediates postsynaptic AMPA-receptor insertion. Overall, the presence of two SNARE-domains confers members of this family the ability to associate to different Qa and R-SNAREs and drive diverse membrane fusion reactions; one member of the family, SNAP-25, has been devoted entirely to Ca2+-triggered fusion and has taken on a number of additional, regulatory roles.
-
Chronic inflammation contributes to neuronal death in Alzheimer's disease (AD) and frontotemporal dementia (FTD). Here we evaluated inflammatory and pro-resolving mediators in AD and behavioural variant of FTD (bvFTD) patients compared with controls, since neuroinflamamtion is a common feature in both diseases. Ninety-eight subjects were included in this study, divided into AD (n = 32), bvFTD (n = 30), and control (n = 36) groups. ⋯ Moreover, reduced plasma levels of AnxA1 were observed in bvFTD compared to AD and controls. There was a significant cleavage of AnxA1 in PBMCs in both dementia groups. The results suggest differential regulation of inflammatory and pro-resolving mediators in bvFTD and AD, while AnxA1 cleavage may impair pro-resolving mechanisms in both groups.