Long-term estrogen therapy worsens the behavioral and neuropathological consequences of chronic brain inflammation.
Alzheimer's disease (AD) is accompanied by chronic neuroinflammation and occurs with greater incidence in postmenopausal women. The increased incidence may be delayed by estrogen replacement therapy (ERT). The authors investigated the interaction of chronic ERT and lipopolysaccharide (LPS)-induced neuroinflammation in the female rat. Ovariectomy did not impair water maze performance; however, addition of chronic ERT or neuroinflammation resulted in an impairment that became exacerbated by the simultaneous occurrence of both conditions. Chronic LPS activated microglia, which was not reduced by ERT. Intact females receiving LPS infusion were not impaired in the water maze and had significantly fewer activated microglia. Results suggest that chronic ERT in postmenopausal women may exacerbate the memory impairment induced by the chronic neuroinflammation associated with AD.
D000704:Analysis of Variance; D000818:Animals; D000943:Antigens, Differentiation / Q000187:drug effects / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D002908:Chronic Disease; D004347:Drug Interactions; D004660:Encephalitis / Q000209:etiology*; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D004967:Estrogens / Q000494:pharmacology; D005260:Female; D008070:Lipopolysaccharides / Q000633:toxicity; D008137:Longitudinal Studies; D018782:Maze Learning / Q000187:drug effects; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D010052:Ovariectomy; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors
D000943:Antigens, Differentiation; D004967:Estrogens; D008070:Lipopolysaccharides; C459465:OX-62 antigen, rat