Affiliations: [a] Research School of Biology, Australian National University, Canberra, ACT, Australia | [b] Geriatric Research, Education and Clinical Center, Veterans Administration Hospital, Madison, WI, USA | [c] Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA | [d] School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia
Correspondence:
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Correspondence to: Ian A. Clark, Ph.D., Research School of Biology, Australian National University, Canberra, ACT 0200, Australia. Tel.: +61 2 6125 4363; E-mail: ian.clark@anu.edu.au. Craig S. Atwood, Ph.D., University of Wisconsin-Madison Medical School, Wm S. Middleton Memorial VA (GRECC 11G), 2500 Overlook Terrace, Madison, WI 53705, USA. Tel.: +608 256 1901; Ext.: 11664; E-mail: csa@medicine.wisc.edu.
Abstract: This commentary addresses a novel mechanism by which aging-related changes in reproductive hormones could mediate their action in the brain. It presents the evidence that dyotic endocrine signals modulate the expression of tumor necrosis factor (TNF) and related cytokines, and that these cytokines are a functionally important downstream link mediating neurodegeneration and dysfunction. This convergence of dyotic signaling on TNF-mediated degeneration and dysfunction has important implications for understanding the pathophysiology of AD, stroke, and traumatic brain disease, and also for the treatment of these diseases.
