Dual effect of beta-amyloid on ?7 and ?4?2 nicotinic receptors controlling the release of glutamate, aspartate and GABA in rat hippocampus.

ABSTRACT:

Background

We previously showed that beta-amyloid (A?), 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 A? (at different concentrations) on the neurotransmitter release stimulated by the activation of pre-synaptic cholinergic nicotinic receptors (nAChRs, ?4?2 and ?7 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 A? considered (10 µM in vivo and 100 nM in vitro). In vivo administration of 100 nM A? (the lowest concentration considered) potentiated the GABA overflow evoked by nicotine. All these effects were specific for A? and for nicotinic secretory stimuli. The in vitro administration of either choline or 5-Iodo-A-85380 dihydrochloride (?7 and ?4?2 nAChRs selective agonists, respectively) elicited the hippocampal release of aspartate, glutamate, and GABA. High A? concentrations (100 nM) inhibited the overflow of all three neurotransmitters evoked by both choline and 5-Iodo-A-85380 dihydrochloride. On the contrary, low A? concentrations (1 nM and 100 pM) selectively acted on ?7 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 A? has relevant neuromodulatory effects, which may span from facilitation to inhibition of stimulated release depending upon the concentration used.

SUBMITTER: Mura E 

PROVIDER: S-EPMC3256170 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature