title: [Pharmacological treatment strategies targeting cognitive impairment associated with aging].
abstract: Amnestic mild cognitive impairment (aMCI) is associated with increased activation in the CA3-dentate region of hippocampus. Excess CA3 activity also occurs in aged rats with memory impairment. Therapies to counter such excess activity might include antiepileptics or agonists for GABA(A) α5 receptors, which regulate tonic inhibition. Use of GABA(A) α5 agonists may seem unexpected because GABA(A) α5 inverse agonists were developed as cognitive enhancers. We found that inverse agonists, while yielding benefit in normal young adult rats, are not effective in treating memory loss in aged rats. Instead, aged rats showed improved memory after treatment with selective GABA(A) α5 agonists and with certain antiepileptics. These benefits of treatment are consistent with the concept that excess activity in the CA3 of the hippocampus is a dysfunctional condition contributing to age-associated memory impairment. Because excess hippocampal activation is also observed in aMCI, our findings support the use of antiepileptic or GABA(A) α5 agonist therapy in aMCI. Such therapy, in addition to memory improvement, may also have disease modifying potential because hippocampal overactivity in aging/MCI predicts further cognitive decline and conversion to Alzheimer's disease.
authors.affiliation: Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, Maryland 21218, USA. mtkoh@jhu.edu
authors.forename: Ming Teng
authors.initials: MT
authors.lastname: Koh
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000188:drug therapy / Q000209:etiology; D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D056654:CA3 Region, Hippocampal / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D058785:GABA-A Receptor Agonists / Q000627:therapeutic use*; D006801:Humans; D051381:Rats
chemical_list: D000927:Anticonvulsants; D058785:GABA-A Receptor Agonists