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Minocycline prevents cholinergic loss in a mouse model of Down's syndrome
Author(s) -
Hunter Christopher L.,
Bachman David,
Granholm AnnCharlotte
Publication year - 2004
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.20250
Subject(s) - minocycline , neuroinflammation , neuroprotection , neurodegeneration , cholinergic , neuroscience , basal forebrain , medicine , cognitive decline , dementia , cholinergic neuron , dementia with lewy bodies , alzheimer's disease , down syndrome , neurology , psychology , disease , biology , psychiatry , antibiotics , microbiology and biotechnology
Individuals with Down's syndrome develop Alzheimer's‐like pathologies comparatively early in life, including progressive degeneration of basal forebrain cholinergic neurons (BFCNs). Cholinergic hypofunction contributes to dementia‐related cognitive decline and remains a target of therapeutic intervention for Alzheimer's disease. In light of this, partial trisomy 16 (Ts65Dn) mice have been developed to provide an animal model of Down's syndrome that exhibits progressive loss of BFCNs and cognitive ability. Another feature common to both Down's syndrome and Alzheimer's disease is neuroinflammation, which may exacerbate neurodegeneration, including cholinergic loss. Minocycline is a semisynthetic tetracycline with antiinflammatory properties that has demonstrated neuroprotective properties in certain disease models. Consistent with a role for inflammatory processes in BFCN degeneration, we have shown previously that minocycline protects BFCNs and improves memory in mice with acute, immunotoxic BFCN lesions. We now report that minocycline treatment inhibits microglial activation, prevents progressive BFCN decline, and markedly improves performance of Ts65Dn mice on a working and reference memory task. Minocycline is an established antiinflammatory and neuroprotective drug and may provide a novel approach to treat specific AD‐like pathologies. Ann Neurol 2004