Epilepsy, amyloid-β, and D1 dopamine receptors

a possible pathogenetic link?

Cinzia Costa, Lucilla Parnetti, Marcello D'Amelio, Alessandro Tozzi, Michela Tantucci, Andrea Romigi, Sabrina Siliquini, Virve Cavallucci, Massimiliano Di Filippo, Petra Mazzocchetti, Claudio Liguori, Annalisa Nobili, Paolo Eusebi, Nicola B. Mercuri, Paolo Calabresi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Experimental and clinical observations indicate that amyloid-β1–42 (Aβ1–42) peptide not only represents a major actor in neurodegenerative mechanisms but also induce hyperexcitation in individual neurons and neural circuits. In this abnormal excitability, possibly leading to seizures, the D1 dopamine (DA) receptors may play a role. Cerebrospinal fluid levels of Aβ1–42 were measured in patients with late-onset epilepsy of unknown etiology. Moreover, the effect of amyloid peptide on the hippocampal epileptic threshold and synaptic plasticity and its link to D1 receptor function were tested in experimental mouse model of cerebral amyloidosis and in acute model of Aβ1–42–induced neurotoxicity. Among 272 evaluated epileptic patients, aged >55 years, 35 suffered from late-onset epilepsy of unknown etiology. In these subjects, cerebrospinal fluid Aβ1–42 levels were measured. The effects of Aβ1–42, amyloid oligomers, and D1 receptor modulation on epileptic threshold were analyzed by electrophysiological recordings in the dentate gyrus of mice hippocampal slices. We found that Aβ1–42 levels were significantly decreased in cerebrospinal fluid of patients with late-onset epilepsy of unknown etiology with respect to controls suggesting the cerebral deposition of this peptide in these patients. Aβ1–42 enhanced epileptic activity in mice through a mechanism involving increased surface expression of D1 receptor, and this effect was mimicked by D1 receptor stimulation and blocked by SCH 23390, a D1 receptor antagonist. Aβ1–42 may contribute to the pathophysiology of late-onset epilepsy of unknown origin. Our preclinical findings indicate that the D1 receptor is involved in mediating the epileptic effects of Aβ1–42. This novel link between Aβ1–42 and D1 receptor signaling might represent a potential therapeutic target.

Original languageEnglish
Pages (from-to)161-171
Number of pages11
JournalNeurobiology of Aging
Volume48
DOIs
Publication statusPublished - Dec 1 2016

Fingerprint

Dopamine D1 Receptors
Amyloid
Epilepsy
Cerebrospinal Fluid
Peptides
Neuronal Plasticity
Dentate Gyrus
Seizures
Theoretical Models

Keywords

  • Alzheimer's disease
  • Aβ oligomers
  • D1 dopamine receptor
  • Epileptic threshold
  • Seizures
  • Transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Epilepsy, amyloid-β, and D1 dopamine receptors : a possible pathogenetic link? / Costa, Cinzia; Parnetti, Lucilla; D'Amelio, Marcello; Tozzi, Alessandro; Tantucci, Michela; Romigi, Andrea; Siliquini, Sabrina; Cavallucci, Virve; Di Filippo, Massimiliano; Mazzocchetti, Petra; Liguori, Claudio; Nobili, Annalisa; Eusebi, Paolo; Mercuri, Nicola B.; Calabresi, Paolo.

In: Neurobiology of Aging, Vol. 48, 01.12.2016, p. 161-171.

Research output: Contribution to journalArticle

Costa, C, Parnetti, L, D'Amelio, M, Tozzi, A, Tantucci, M, Romigi, A, Siliquini, S, Cavallucci, V, Di Filippo, M, Mazzocchetti, P, Liguori, C, Nobili, A, Eusebi, P, Mercuri, NB & Calabresi, P 2016, 'Epilepsy, amyloid-β, and D1 dopamine receptors: a possible pathogenetic link?', Neurobiology of Aging, vol. 48, pp. 161-171. https://doi.org/10.1016/j.neurobiolaging.2016.08.025
Costa, Cinzia ; Parnetti, Lucilla ; D'Amelio, Marcello ; Tozzi, Alessandro ; Tantucci, Michela ; Romigi, Andrea ; Siliquini, Sabrina ; Cavallucci, Virve ; Di Filippo, Massimiliano ; Mazzocchetti, Petra ; Liguori, Claudio ; Nobili, Annalisa ; Eusebi, Paolo ; Mercuri, Nicola B. ; Calabresi, Paolo. / Epilepsy, amyloid-β, and D1 dopamine receptors : a possible pathogenetic link?. In: Neurobiology of Aging. 2016 ; Vol. 48. pp. 161-171.
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