Estrogen in Clinical Trials for Dementia of Alzheimer Type

  • Nobuyoshi Hagino
  • Takeyoshi Ohkura
  • Kunihiro Isse
  • Kenji Akasawa
  • Makoto Hamamoto
Part of the Advances in Behavioral Biology book series (ABBI, volume 44)


Estrogen is the female steroid hormone which is produced in the ovary and which circulates in the blood stream. The specific proteins which bind to estrogen are distributed in the limbic brain, forebrain, hypothalamus, midbrain and anterior pituitary, as well as in organs such as the ovary and uterus. Estrogen modulates the limbic brain, controls hypothalamo-pituitary-ovarian function, and regulates cyclic release of estrogen from the ovary in women. Lower levels of estrogen act on neural function to bring the onset of puberty and to initiate ovarian cyclicity. In the reproductive period, women ovulate periodically, and they are able to become pregnant and lactate. Once the ovary reaches the time of cessation of the cyclicity, the ovary produces less estrogen and women enter the menopausal period. One of the major symptoms of menopausal women is dementia of Alzheimer type(DAT). The symptoms are an impairment of intelligence and performance (psychological symptoms); impairment of memory, language disintegration, disturbance of praxis and gnosis (neuro-psychological symptoms); as well as epileptic seizures and motor disturbance (neurological symptoms). Some of these symptoms are associated with a dysfunction of the limbic brain and forebrain. Menopausal women have a twice as much higher incidence of DAT as compared with men of the same age. About twenty years ago, we observed that estrogen modulates the activity of cholinergic neurons in the limbic brain and hypothalamus in rats. This evidence prompted a study of the neuroendocrinological approach to investigate adequate therapeutics for treatments for dementia of Alzheimer type (DAT) in women. At first we examined the effect of estrogen on the activity of cholinergic neurons in the septo-hippocampal system and their function in rats. Secondarily, we studied the effect of estrogen on nicotine acetylcholine receptors (nAchRs) synthesis. Finally, we applied our working hypothesis to examine the effect of estrogen on post-menopausal women with DAT.


Single Photon Emission Compute Tomography Cholinergic Neuron Estrogen Replacement Therapy Estrogen Treatment Dorsal Hippocampus 
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Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Nobuyoshi Hagino
    • 1
  • Takeyoshi Ohkura
    • 1
  • Kunihiro Isse
    • 2
  • Kenji Akasawa
    • 2
  • Makoto Hamamoto
    • 3
  1. 1.Department of Cellular and Structural Biology The University of Texas Health ScienceCenter at San AntonioTexasUSA
  2. 2.Department of PsychiatryTokyo Metropolitan Tama Geriatric HospitalTokyoJapan
  3. 3.Department of NeurologyTokyo Metropolitan Tama Geriatric HospitalTokyoJapan

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