title: Dual effect of beta-amyloid on α7 and α4β2 nicotinic receptors controlling the release of glutamate, aspartate and GABA in rat hippocampus.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Department of Drug Sciences, Centre of Excellence in Applied Biology, University of Pavia, Pavia, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Mura
authors.forename: Stefania
authors.initials: S
authors.lastname: Zappettini
authors.forename: Stefania
authors.initials: S
authors.lastname: Preda
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Biundo
authors.forename: Cristina
authors.initials: C
authors.lastname: Lanni
authors.forename: Massimo
authors.initials: M
authors.lastname: Grilli
authors.forename: Anna
authors.initials: A
authors.lastname: Cavallero
authors.forename: Guendalina
authors.initials: G
authors.lastname: Olivero
authors.forename: Alessia
authors.initials: A
authors.lastname: Salamone
authors.forename: Stefano
authors.initials: S
authors.lastname: Govoni
authors.forename: Mario
authors.initials: M
authors.lastname: Marchi
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000378:metabolism*; D013997:Time Factors; D014701:Veratridine / Q000494:pharmacology; D064569:alpha7 Nicotinic Acetylcholine Receptor; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D018377:Neurotransmitter Agents; D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; C403531:nicotinic receptor alpha4beta2; D001224:Aspartic Acid; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D009538:Nicotine; D014701:Veratridine; D011188:Potassium