1993 Fiscal Year Final Research Report Summary
Neurochemical and Pharmacological Studies on the Disturbances in Serotonergic systems in Alzheimer-type Dementia
| Project/Area Number |
03454293
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Psychiatric science
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| Research Institution | Juntendo University School of Medicine |
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Principal Investigator |
ARAI Heii Juntendo University School of Medicine, Lecturer, 医学部, 講師 (50167988)
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| Co-Investigator(Kenkyū-buntansha) |
KIMURA Michihiro Juntendo University School of Medicine, Asistant, 医学部, 助手 (50234381)
NOGUCHI Iwahide Juntendo University School of Medicine, Asistant, 医学部, 助手 (30237820)
MINAMI Masayuki Juntendo University School of Medicine, Asistant, 医学部, 助手 (50229770)
IWAMOTO Norihiko Juntendo University School of Medicine, Asistant, 医学部, 助手 (60211067)
ICHIMIYA Yosuke Juntendo University School of Medicine, Lecturer, 医学部, 講師 (10184631)
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| Project Period (FY) |
1991 – 1993
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| Keywords | Alzheimer's disease / Senile Dementia / Neurotransmitter / Serotonin / Neuropeptide / Human Brain |
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| Research Abstract |
Neurochemical and pharmacological investigations were performed on rat brains and postmortem human brains obtained from Alzheimer-type dementia(ATD) patients in order to understand the pathogenesis of ATD.Selective serotonin reuptake inhibitor(ZD211) given orally(30mg/kg) decreased corticotropin releasing factor-like immunoreactivity(LI) and increased galanin-LI in rat hypothalamus, adorenocorticotropic hormone-LI in serum and corticosteron-LI in serum. These findings suggest the stimulation of hypothalamus-pituitary-adrenal cortex axis by the serotonergic system. Neurochemical examinations on postmortem brains revealed that changes in the cholinergic and serotonergic systems in the early-onset ATD brains were much severer than those in the late-onset ATD brains. These findings as well as changes in neuropeptides in ATD brains may suggest the usefulness of serotonin reuptake inhibitors as a therapeutic drug for ATD patients, in particular the early-onset ATD subgroup. We also examined the correlations between biogenic amine concentration in brain and those in plasma. However, none of the peripheral marker except for homovanillic acid was found to be useful to understand changes in brains. Another clinical finding found in the present study was the wide variations of plasma-concentrations of brain metabolism-activating agents in patients with organic brains disorders. These features should be taken into considerations when serotonergic drugs are induced clinically for ATD patients. In conclusion, it was suggested that the serotonergic system as well as the interactions between neurotransmitters should receive attention in terms of therapeutic strategies for ATD.
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