title: Beyond the Hypothesis of Serum Anticholinergic Activity in Alzheimer's Disease: Acetylcholine Neuronal Activity Modulates Brain-Derived Neurotrophic Factor Production and Inflammation in the Brain.
abstract: The brain of Alzheimer's disease (AD) patients is characterized by neurodegeneration, especially an acetylcholine (ACh) neuronal deficit with accumulation of β-amyloid protein, which leads to oxygen stress and inflammation. The active oxygen directly damages the neuron by increasing intracellular Ca(2+). The inflammation is due to activation of the microglia, thereby producing cytokines which inhibit the production of brain-derived neurotrophic factor (BDNF). As the BDNF acts by neuronal protection, synaptogenesis and neurogenesis, the reduction of BDNF in the brain of AD patients worsens the symptoms of AD. On the other hand, treatment of AD patients with a cholinesterase inhibitor enhances ACh activity and inhibits inflammation. Then the expression of BDNF is restored and neuroprotection reestablished. However, there are several reports which showed controversial results concerning the relationship between BDNF and AD. We speculate that BDNF is related to some neurocognitive process and reflects neuronal activity in other neurodegenerative and neuropsychiatric disorders and that in the mild cognitive impairment stage, BDNF and choline acetyltransferase (ChAT) activities are hyperactivated because of a compensatory mechanism of AD pathology. In contrast, in the mild stage of AD, BDNF and ChAT activity are downregulated.
authors.affiliation: Department of Pharmaceutical Therapeutics, Division of Clinical Pharmacy, School of Pharmacy, Showa University, Tokyo, Japan.
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Hachisu
authors.forename: Kimiko
authors.initials: K
authors.lastname: Konishi
authors.forename: Misa
authors.initials: M
authors.lastname: Hosoi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tani
authors.forename: Hiroi
authors.initials: H
authors.lastname: Tomioka
authors.forename: Atsuko
authors.initials: A
authors.lastname: Inamoto
authors.forename: Sousuke
authors.initials: S
authors.lastname: Minami
authors.forename: Takuji
authors.initials: T
authors.lastname: Izuno
authors.forename: Kaori
authors.initials: K
authors.lastname: Umezawa
authors.forename: Kentaro
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Koji
authors.initials: K
authors.lastname: Hori
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D004660:Encephalitis / Q000209:etiology*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D018680:Cholinergic Antagonists; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine