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Neurotoxicity Research

, Volume 6, Issue 4, pp 299–309 | Cite as

Ovariectomy combined with amyloid β1-42 impairs memory by decreasing acetylcholine release and α7nAChR Expression without induction of apoptosis in the hippocampus CA1 neurons of rats

  • Katsunori Iwasaki
  • Izzettin Hatip-Al-Khatib
  • Nobuaki Egashira
  • Yuki Akiyoshi
  • Takashi Arai
  • Kenichi Mishima
  • Yuki Takagaki
  • Keiichiro Inui
  • Michihiro Fujiwara
Article

Abstract

In this study, the effect of ovariectomy and amyloid P1-42 (Aβ1-42)on eight-armed radial maze performance, acetylcholine (ACh) release, α7nACh receptor (α7nAChR), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) expression, and apoptosis of CA1 neurons in the dorsal hippocampus were investigated in rat. The results showed that the dorsal hippocampus of sham rats contains 136.7 ± 16.7 to 160.4 ± 21.1 fmol/μl ACh, and respective 201 ± 22.9 and 416.6 ± 66.3 expression of mRNA for α7nAChR and GAPDH. Ovariectomy alone, after 4 weeks, did not impair memory, and neither induced apoptosis nor changed the basal ACh release. On the other hand, Aβ1-42 (600 pmol/10 μl/body/day i.c.v. for 7 days) impaired memory, an effect characterized by increased error choices and reduced (50–59%) ACh release, but only with slight apoptosis. Moreover, ovariectomy combined with Aβ1-42 induced memory impairment characterized by decreased numbers of correct choices and increased numbers of errors. This effect was accompanied by a decrease of the basal ACh level (67%), α7nAChR mRNA expression (52%) and α7nAChR/GAPDH ratio (44%) without induction of apoptosis in the dorsal hippocampus. The high K+-evoked ACh release was not altered in ovariectomized rats, but was decreased by Aβ1-42 (43%) and ovariectomy + Aβ1-42 (80%). These results suggest that ovariectomy-induced hormonal deprivation after 4 weeks, when accompanied by Aβ1-42 accumulation in the dorsal hippocampus, could impair memory by decreasing ACh release and α7nAChR expression without inducing apoptosis in the CA1 field of the dorsal hippocampus.

Keywords

Ovariectomy Amyloid β1-42 Acetylcholine Hippocampus CA1 Memory Apoptosis α7nAChR 

Abbreviations

1-42

Amyloid beta1-42 peptide

Ach

Acetylcholine

α7nAChR

alpha7 nicotinic acetylcholine receptor

AD

Alzheimer’s disease

CC

Correct choice

DH

Dorsal hippocampus

EC

Error choices

GAPDH

Glyceraldehyde 3-phosphate dehydrogenase

i.c.v.

Intracerebroventricular infusion

OVX

Ovariectomy

RAM

Eight-arm radial maze task

RT-PCR

Reverse transcription-polymerase chain reaction

TUNEL test

Terminal deoxynucleotidyl transferase (TdT)-mediated fluorescein-deoxyuridinetriphosphate (dUTP) nick-end labeling.

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Copyright information

© Springer 2004

Authors and Affiliations

  • Katsunori Iwasaki
    • 1
    • 3
  • Izzettin Hatip-Al-Khatib
    • 2
    • 3
  • Nobuaki Egashira
    • 1
  • Yuki Akiyoshi
    • 1
  • Takashi Arai
    • 1
  • Kenichi Mishima
    • 1
  • Yuki Takagaki
    • 1
  • Keiichiro Inui
    • 1
  • Michihiro Fujiwara
    • 1
    • 3
  1. 1.Department of Neuropharmacology, Faculty of Pharmaceutical SciencesFukuoka UniversityJonan-KuJapan
  2. 2.Department of Pharmacology, Division of Internal Medicine, Faculty of MedicinePamukkale UniversityDenizliTurkey
  3. 3.Advanced Material InstituteFukuoka UniversityFukuokaJapan

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