Impaired firing properties of dentate granule neurons in an Alzheimer’s disease animal model are rescued by PPARγ agonism

Miroslav N. Nenov, Filippo Tempia, Larry Denner, Kelly T. Dineley, Fernanda Laezza

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Early cognitive impairment in Alzheimer’s disease (AD) correlates with medial temporal lobe dysfunction, including two areas essential for memory formation: the entorhinal cortex and dentate gyrus (DG). In the Tg2576 animal model for AD amyloidosis, activation of the peroxisome proliferatoractivated receptor-gamma (PPARγ) with rosiglitazone (RSG) ameliorates hippocampus-dependent cognitive impairment and restores aberrant synaptic activity at the entorhinal cortex to DG granule neuron inputs. It is unknown, however, whether intrinsic firing properties of DG granule neurons in these animals are affected by amyloid-β pathology and if they are sensitive to RSG treatment. Here, we report that granule neurons from 9-mo-old wild-type and Tg2576 animals can be segregated into two cell types with distinct firing properties and input resistance that correlate with less mature type I and more mature type II neurons. The DG type I cell population was greater than type II in wild-type littermates. In the Tg2576 animals, the type I and type II cell populations were nearly equal but could be restored to wildtype levels through cognitive enhancement with RSG. Furthermore, Tg2576 cell firing frequency and spike after depolarization were decreased in type I and increased in type II cells, both of which could also be restored to wild-type levels upon RSG treatment. That these parameters were restored by PPARγ activation emphasizes the therapeutic value of RSG against early AD cognitive impairment.

Original languageEnglish (US)
Pages (from-to)1712-1726
Number of pages15
JournalJournal of neurophysiology
Volume113
Issue number6
DOIs
StatePublished - Mar 15 2015

Keywords

  • Alzheimer’s disease
  • Dentate gyrus
  • Excitability
  • Patch clamp
  • Peroxisome proliferator-activated receptor-γ

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology

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