Sustained High Body Temperature Exacerbates Cognitive Function and Alzheimer's Disease-related Pathologies

Overview

Journal Sci Rep

Specialty Science

Date 2022 Jul 19

PMID 35851831

Authors

Cha-Gyun Jung

Reiko Kato

Chunyu Zhou

Mona Abdelhamid

Esraa Ibrahim A Shaaban

Hitoshi Yamashita

Makoto Michikawa

Affiliations

Soon will be listed here.

Abstract

Global warming is a serious public health threat to people worldwide. High body temperature is one of the important risk factors for Alzheimer's disease (AD), and the body temperature of AD patients has been found to be significantly higher than that of elderly control subjects. However, the effects of high body temperature on cognitive function and AD pathologies have not been completely elucidated. We report here that Tg2576 mice housed at a high ambient temperature of 30 °C for 13 months showed an increase in the body temperature, which is accompanied by memory impairment and an enhancement of amyloid-β peptides (Aβ) generation through the upregulation of β-site APP cleaving enzyme 1 (BACE1) level and decrease in the level of an Aβ-degrading enzyme, neprilysin (NEP) in the brain, compared with those of Tg2576 mice at 23 °C. High body temperature also increased the levels of heat shock proteins (HSPs), stress-stimulated kinases such as JNK, and total tau, leading to the enhancement of tau phosphorylation at 30 °C. Taken together, our findings suggest that high body temperature exacerbates cognitive function and AD pathologies, which provides a mechanistic insight for its prevention.

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References

Klaffke S, Staedt J . Sundowning and circadian rhythm disorders in dementia. Acta Neurol Belg. 2007; 106(4):168-75. View

Pearson G, Robinson F, Beers Gibson T, Xu B, Karandikar M, Berman K . Mitogen-activated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev. 2001; 22(2):153-83. DOI: 10.1210/edrv.22.2.0428. View

Kang J, Lim M, Bateman R, Lee J, Smyth L, Cirrito J . Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science. 2009; 326(5955):1005-7. PMC: 2789838. DOI: 10.1126/science.1180962. View

Assal F, Cummings J . Neuropsychiatric symptoms in the dementias. Curr Opin Neurol. 2002; 15(4):445-50. DOI: 10.1097/00019052-200208000-00007. View

Katsuno M, Sang C, Adachi H, Minamiyama M, Waza M, Tanaka F . Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease. Proc Natl Acad Sci U S A. 2005; 102(46):16801-6. PMC: 1275598. DOI: 10.1073/pnas.0506249102. View

Wang S, Wang R, Chen L, Bennett D, Dickson D, Wang D . Expression and functional profiling of neprilysin, insulin-degrading enzyme, and endothelin-converting enzyme in prospectively studied elderly and Alzheimer's brain. J Neurochem. 2010; 115(1):47-57. PMC: 2939954. DOI: 10.1111/j.1471-4159.2010.06899.x. View

Carrettiero D, Santiago F, Motzko-Soares A, Almeida M . Temperature and toxic Tau in Alzheimer's disease: new insights. Temperature (Austin). 2016; 2(4):491-8. PMC: 4843920. DOI: 10.1080/23328940.2015.1096438. View

Zhu X, Lee H, Raina A, Perry G, Smith M . The role of mitogen-activated protein kinase pathways in Alzheimer's disease. Neurosignals. 2003; 11(5):270-81. DOI: 10.1159/000067426. View

Iwata N, Tsubuki S, Takaki Y, Watanabe K, Sekiguchi M, Hosoki E . Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition. Nat Med. 2000; 6(2):143-50. DOI: 10.1038/72237. View

10.

Westerman M, Mariash A, Kotilinek L, Kawarabayashi T, Younkin L, Carlson G . The relationship between Abeta and memory in the Tg2576 mouse model of Alzheimer's disease. J Neurosci. 2002; 22(5):1858-67. PMC: 6758862. View

11.

Touitou Y, Reinberg A, Bogdan A, Auzeby A, Beck H, TOUITOU C . Age-related changes in both circadian and seasonal rhythms of rectal temperature with special reference to senile dementia of Alzheimer type. Gerontology. 1986; 32(2):110-8. DOI: 10.1159/000212774. View

12.

Dou F, Netzer W, Tanemura K, Li F, Hartl F, Takashima A . Chaperones increase association of tau protein with microtubules. Proc Natl Acad Sci U S A. 2003; 100(2):721-6. PMC: 141063. DOI: 10.1073/pnas.242720499. View

13.

Maroni P, Bendinelli P, Tiberio L, Rovetta F, Piccoletti R, Schiaffonati L . In vivo heat-shock response in the brain: signalling pathway and transcription factor activation. Brain Res Mol Brain Res. 2003; 119(1):90-9. DOI: 10.1016/j.molbrainres.2003.08.018. View

14.

Jinwal U, Akoury E, Abisambra J, OLeary 3rd J, Thompson A, Blair L . Imbalance of Hsp70 family variants fosters tau accumulation. FASEB J. 2012; 27(4):1450-9. PMC: 3606536. DOI: 10.1096/fj.12-220889. View

15.

Okawa M, Mishima K, Hishikawa Y, Hozumi S, Hori H, Takahashi K . Circadian rhythm disorders in sleep-waking and body temperature in elderly patients with dementia and their treatment. Sleep. 1991; 14(6):478-85. DOI: 10.1093/sleep/14.6.478. View

16.

Paola D, Domenicotti C, Nitti M, Vitali A, Borghi R, Cottalasso D . Oxidative stress induces increase in intracellular amyloid beta-protein production and selective activation of betaI and betaII PKCs in NT2 cells. Biochem Biophys Res Commun. 2000; 268(2):642-6. DOI: 10.1006/bbrc.2000.2164. View

17.

Bombois S, Derambure P, Pasquier F, Monaca C . Sleep disorders in aging and dementia. J Nutr Health Aging. 2010; 14(3):212-7. DOI: 10.1007/s12603-010-0052-7. View

18.

Sigurdsson E, Knudsen E, Asuni A, Fitzer-Attas C, Sage D, Quartermain D . An attenuated immune response is sufficient to enhance cognition in an Alzheimer's disease mouse model immunized with amyloid-beta derivatives. J Neurosci. 2004; 24(28):6277-82. PMC: 6729550. DOI: 10.1523/JNEUROSCI.1344-04.2004. View

19.

Taslima F, Jung C, Zhou C, Abdelhamid M, Abdullah M, Goto T . Tooth Loss Induces Memory Impairment and Gliosis in App Knock-In Mouse Models of Alzheimer's Disease. J Alzheimers Dis. 2021; 80(4):1687-1704. DOI: 10.3233/JAD-201055. View

20.

Dickey C, Kamal A, Lundgren K, Klosak N, Bailey R, Dunmore J . The high-affinity HSP90-CHIP complex recognizes and selectively degrades phosphorylated tau client proteins. J Clin Invest. 2007; 117(3):648-58. PMC: 1794119. DOI: 10.1172/JCI29715. View