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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

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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.

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Abbreviations

Aβ1-42 :

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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Authors and Affiliations

  1. Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1 Nanakuma, 814-0180, Jonan-Ku, Fukuoka, Japan

    Katsunori Iwasaki, Nobuaki Egashira, Yuki Akiyoshi, Takashi Arai, Kenichi Mishima, Yuki Takagaki, Keiichiro Inui & Michihiro Fujiwara

  2. Department of Pharmacology, Division of Internal Medicine, Faculty of Medicine, Pamukkale University, 20070, Denizli, Turkey

    Izzettin Hatip-Al-Khatib

  3. Advanced Material Institute, Fukuoka University, 814-0180, Fukuoka, Japan

    Katsunori Iwasaki, Izzettin Hatip-Al-Khatib & Michihiro Fujiwara

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  1. Katsunori Iwasaki
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  2. Izzettin Hatip-Al-Khatib
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Correspondence to Katsunori Iwasaki.

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Iwasaki, K., Hatip-Al-Khatib, I., Egashira, N. et al. 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. neurotox res 6, 299–309 (2004). https://doi.org/10.1007/BF03033440

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  • DOI: https://doi.org/10.1007/BF03033440

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