Dual Effect of Beta-Amyloid on α7 and α4β2 Nicotinic Receptors Controlling the Release of Glutamate, Aspartate and GABA in Rat Hippocampus

BACKGROUND: We 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/FINDINGS: WE 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/SIGNIFICANCE: The 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

A survey of anatomical items relevant to the practice of rheumatology: upper extremity, head, neck, spine, and general concepts.

This study aimed to identify the anatomical items of the upper extremity and spine that are potentially relevant to the practice of rheumatology. Ten rheumatologists interested in clinical anatomy who published, taught, and/or participated as active members of Clinical Anatomy Interest groups (six seniors, four juniors), participated in a one-round relevance Delphi exercise. An initial, 560-item list that included 45 (8.0 %) general concepts items; 138 (24.8 %) hand items; 100 (17.8 %) forearm and elbow items; 147 (26.2 %) shoulder items; and 130 (23.2 %) head, neck, and spine items was compiled by 5 of the participants. Each item was graded for importance with a Likert scale from 1 (not important) to 5 (very important). Thus, scores could range from 10 (1 × 10) to 50 (5 × 10). An item score of ≥40 was considered most relevant to competent practice as a rheumatologist. Mean item Likert scores ranged from 2.2 ± 0.5 to 4.6 ± 0.7. A total of 115 (20.5 %) of the 560 initial items reached relevance. Broken down by categories, this final relevant item list was composed by 7 (6.1 %) general concepts items; 32 (27.8 %) hand items; 20 (17.4 %) forearm and elbow items; 33 (28.7 %) shoulder items; and 23 (17.6 %) head, neck, and spine items. In this Delphi exercise, a group of practicing academic rheumatologists with an interest in clinical anatomy compiled a list of anatomical items that were deemed important to the practice of rheumatology. We suggest these items be considered curricular priorities when training rheumatology fellows in clinical anatomy skills and in programs of continuing rheumatology education