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
| Autor: | Masayuki Tani, Sousuke Minami, Kimiko Konishi, Atsuko Inamoto, Takuji Izuno, Kentaro Horiuchi, Mitsugu Hachisu, Koji Hori, Misa Hosoi, Hiroi Tomioka, Kaori Umezawa |
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| Rok vydání: | 2015 |
| Předmět: |
medicine.medical_specialty
Neuroprotection Cholinergic Antagonists Choline O-Acetyltransferase Alzheimer Disease Neurotrophic factors Internal medicine medicine Animals Humans Neurons Brain-derived neurotrophic factor Brain-Derived Neurotrophic Factor Neurodegeneration Brain medicine.disease Choline acetyltransferase Acetylcholine Endocrinology medicine.anatomical_structure nervous system Neurology Encephalitis Neurology (clinical) Neuron Alzheimer's disease Psychology Neuroscience medicine.drug |
| Zdroj: | Neurodegenerative Diseases. 15:182-187 |
| ISSN: | 1660-2862 1660-2854 |
| DOI: | 10.1159/000381531 |
| Popis: | 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 Ca2+. 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. |
| Databáze: | OpenAIRE |
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