Studies in Animal Models of the Effects of Anesthetics on Behavior, Biochemistry, and Neuronal Cell Death

Issue title: Anesthetics and Alzheimer's Disease

Guest editors: Pravat K. Mandalx and Vincenzo Fodaley

Article type: Review Article

Authors: Mena, María Ángeles^a | Perucho, Juan^a | Rubio, Isabel^b | de Yébenes, Justo Garcia^{b; *}

Affiliations: [a] Department of Neurobiology, Hospital Ramon y Cajal, and CIBERned, Madrid, Spain | [b] Department of Neurology, Hospital Ramon y Cajal, and CIBERned, Madrid, Spain | [x] Neurospectroscopy and Neuroimaging Laboratory, National Brain Research Center, Manesar, Gurgaon, India | [y] Department of Neurosciences, Psychiatric and Anesthesiological Sciences, University of Messina, Policlinico G. Martino, Messina, Italy

Correspondence: [*] Correspondence to: Dr. J. García de Yébenes, Department of Neurology, Hospital Ramón y Cajal, Ctra. de Colmenar, Km. 9, Madrid 28034, Spain. Tel.: +34 91 336 88 33; Fax: +34 91 336 90 16; E-mail: [email protected].

Abstract: Recent clinical studies have suggested that there is an increased risk of Alzheimer's disease (AD) in patients undergoing surgical interventions, but it is unknown whether this effect is related to anesthesia, cardiovascular complications of surgery, or associated conditions such as hypothermia. In addition, many patients, especially the elderly, present persistent post-operative cognitive deterioration after anesthesia, without clear complications during surgery. Experimental studies in animals may be helpful to dissect the pathogenic role of the different factors involved in surgery. Here, we review studies on the effects of anesthesia on neuronal function performed in tissue culture and in experimental animals. Several studies have shown that a small inhalation of anesthetics induces activation of caspases and cell toxicity on glioma and pheochromocitoma cells in culture, which is prevented by treatment with the metal chelating agent clioquinol. Exposure of old rodents to anesthesia produced memory deficits and increased levels of amyloid-β (Aβ) peptide and phosphorylated tau in brain. The effects of long term or short term repetitive exposure to small molecular weight anesthetics are more severe in transgenic AβPPswe than in wild type mice. In the former, low molecular weight increased the number of TUNEL+ apoptotic cells and the ratio of pro-apoptotic proteins in hippocampus; reduced astroglial and increased microglial responses; increased Aβ aggregates and high molecular weight peptides; abnormal chaperone responses and reduced autophagy. In conclusion, anesthetic gases induce changes which may reproduce AD pathology in mice with mutations which produced AD. It would be interesting to know whether anesthetics are risky for subjects with special genetic risk factors.

Keywords: Alzheimer's disease, amyloid pathology, AβPPswe mice, apoptotic cell death, autophagy, cognitive deficits, chaperones, glial cells, isoflurane, post operative cognitive dysfunction, presenilin-1

DOI: 10.3233/JAD-2010-100822

Journal: Journal of Alzheimer's Disease, vol. 22, no. s3, pp. S43-S48, 2010