Amyloid Beta Peptide (Aβ1-42) Reverses the Cholinergic Control of Monocytic IL-1β Release

Amyloid-β peptide (Aβ1-42), the cleavage product of the evolutionary highly conserved amyloid precursor protein, presumably plays a pathogenic role in Alzheimer’s disease. Aβ1-42 can induce the secretion of the pro-inflammatory cytokine intereukin-1β (IL-1β) in immune cells within and out of the nervous system. Known interaction partners of Aβ1-42 are α7 nicotinic acetylcholine receptors (nAChRs). The physiological functions of Aβ1-42 are, however, not fully understood. Recently, we identified a cholinergic mechanism that controls monocytic release of IL-1β by canonical and non-canonical agonists of nAChRs containing subunits α7, α9, and/or α10. Here, we tested the hypothesis that Aβ1-42 modulates this inhibitory cholinergic mechanism. Lipopolysaccharide-primed monocytic U937 cells and human mononuclear leukocytes were stimulated with the P2X7 receptor agonist 2′(3′)-O-(4-benzoylbenzoyl)adenosine-5′-triphosphate triethylammonium salt (BzATP) in the presence or absence of nAChR agonists and Aβ1-42. IL-1β concentrations were measured in the supernatant. Aβ1-42 dose-dependently (IC50 = 2.54 µM) reversed the inhibitory effect of canonical and non-canonical nicotinic agonists on BzATP-mediated IL-1β-release by monocytic cells, whereas reverse Aβ42-1 was ineffective. In conclusion, we discovered a novel pro-inflammatory Aβ1-42 function that enables monocytic IL-1β release in the presence of nAChR agonists. These findings provide evidence for a novel physiological function of Aβ1-42 in the context of sterile systemic inflammation

Contrasting roles for lateral and ventromedial prefrontal cortex in transient and dispositional affective experience

Prefrontal cortex (PFC) has been implicated in the experience and regulation of emotional states. Emotional experience is a complex construct, encompassing a range of more specific processes. This exploratory study aimed to delineate which (if any) aspects of emotional experience rely critically on either the ventromedial frontal (VMF) or lateral frontal (LF) lobes. The affective experience of individuals with damage to these regions was surveyed in detail using several measures and compared with that of control participants. Dependent measures included subjective and observer ratings of both dispositional affect and transient responses to laboratory mood inductions. VMF damage was associated with greater negative dispositional affect relative to controls and to individuals with LF damage; however, transient responses to emotional stimuli were largely normal. In contrast, LF damage was associated with an exaggerated subjective reactivity to sad emotional stimuli relative to control participants, but normal dispositional affect. Interestingly, neither form of PFC damage affected spontaneous emotion recovery following the mood inductions. These findings suggest a role for VMF in modulating dispositional negative affect; in contrast, LF areas appear to be critical in regulating transient emotional responses while emotional stimuli are present. This study also illustrates the dissociability of different aspects of emotional experience in patients with focal brain injury

Imaging Evaluation of Acute Traumatic Brain Injury

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Imaging plays an important role in the evaluation, diagnosis, and triage of patients with TBI. Recent studies suggest that it will also help predict patient outcomes. TBI consists of multiple pathoanatomical entities. Here we review the current state of TBI imaging including its indications, benefits and limitations of the modalities, imaging protocols, and imaging findings for each these pathoanatomic entities. We also briefly survey advanced imaging techniques, which include a number of promising areas of TBI research

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

International audienc