Associations among the TREM-1 Pathway, Tau Hyperphosphorylation, Prolactin Expression, and Metformin in Diabetes Mice

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Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: July 07, 2021
Accepted: November 08, 2021
Published online: February 07, 2022

Number of Print Pages: 10
Number of Figures: 3
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: https://www.karger.com/NIM

Abstract

Introduction: Diabetes mellitus (DM) is a risk factor for Alzheimer’s disease (AD). Increasing evidence indicates that the triggering receptor expressed on myeloid cells (TREM)-1 amplifies chronic inflammation, as well as the roles of prolactin (PRL) and metformin (MET) in tau hyperphosphorylation. However, the associations among TREM-1, tau hyperphosphorylation, PRL expression, and MET in DM remain unclear. Methods: Streptozotocin was used to induce experimental DM in C57BL/6N mice. MET was orally administered at a dose of 400 mg/kg body weight for 6 weeks prior to hippocampal collection in DM mice. Various parameters pertaining to the TREM-1 pathway, tau hyperphosphorylation, PRL, and related factors were analyzed. Results: Quantitative polymerase chain reaction and Western blot analysis demonstrated that the expression levels of TREM-1, DAP12, casp1, interleukin-1β, Cox2, inducible nitric oxide synthase, pituitary transcriptional factor-1 (Pit-1), and PRL were significantly increased in the hippocampus of DM mice; the expression levels of these pro-inflammatory mediators, PRL receptor (PRLR) short or long (PRLR-S and PRLR-L), and PRL regulatory element-binding (Preb) protein in DM mice treated with MET (DM + MET) were significantly decreased compared with those in control (CON) mice. The levels of p-Tau and glycogen synthase kinase-3 in the DM group were significantly higher than those in the CON group and significantly lower than those in the DM + MET group. Conclusion: We confirmed the therapeutic potential of MET for both DM and neurodegeneration. Our findings shed new light on the effects of DM on the pathophysiology of AD via the TREM-1 pathway and PRL expression. Thus, an improved understanding of the TREM-1 pathway in hyperglycemic conditions, as well as PRL, Preb, Pit-1, PRLR-L, and PRLR-S gene expression in the liver, brain, and other sites, may help unravel the pathogenesis of insulin resistance and neurodegeneration.

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References McCrimmon RJ, Ryan CM, Frier BM. Diabetes and cognitive dysfunction. Lancet. 2012;379(9833):2291–9. Wennberg AM, Gottesman RF, Kaufmann CN, Albert MS, Chen-Edinboro LP, Rebok GW, et al. Diabetes and cognitive outcomes in a nationally representative sample: the National Health and Aging Trends Study. Int Psychogeriatr. 2014;26(10):1729. Formiga F, Ferrer A, Padrós G, Corbella X, Cos L, Sinclair AJ, et al. Diabetes mellitus as a risk factor for functional and cognitive decline in very old people: the Octabaix study. J Am Med Dir Assoc. 2014;15(12):924–8. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004;61(5):661–6. Elahi M, Hasan Z, Motoi Y, Matsumoto SE, Ishiguro K, Hattori N. Region-specific vulnerability to oxidative stress, neuroinflammation, and tau hyperphosphorylation in experimental diabetes mellitus mice. J Alzheimers Dis. 2016;51(4):1209–24. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC, Baldwin J, et al. Initial sequencing and analysis of the human genome. Nature. 2001;412(6846):565–6. Erratum in: Nature. 2001;409:860–921. Ramos-Martinez E, Ramos-Martínez I, Molina-Salinas G, Zepeda-Ruiz WA, Cerbon M. The role of prolactin in central nervous system inflammation. Rev Neurosci. 2021;32(3):323–40. Balbach L, Wallaschofski H, Völzke H, Nauck M, Dörr M, Haring R. Serum prolactin concentrations as risk factor of metabolic syndrome or type 2 diabetes? BMC Endocr Disord. 2013;13(1):12. Nguyen HD, Yu BP, Hoang NHM, Jo WH, Young Chung H, Kim MS. Prolactin and its altered action in Alzheimer’s disease and Parkinson’s disease. Neuroendocrinology. 2021. Epub ahead of print. Cabrera-Reyes EA, Vanoye–Carlo A, Rodríguez-Dorantes M, Vázquez-Martínez ER, Rivero-Segura NA, Collazo-Navarrete O, et al. Transcriptomic analysis reveals new hippocampal gene networks induced by prolactin. Sci Rep. 2019;9(1):1–12. Rocchetti J, Isingrini E, Dal Bo G, Sagheby S, Menegaux A, Tronche F, et al. Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus. Biol Psychiatry. 2015;77(6):513–25. Fliss MS, Hinkle PM, Bancroft C. Expression cloning and characterization of PREB (prolactin regulatory element binding), a novel WD motif DNA-binding protein with a capacity to regulate prolactin promoter activity. Mol Endocrinol. 1999;13(4):644–57. Muraoka T, Murao K, Imachi H, Yu X, Li J, Wong NC, et al. PREB regulates transcription of pancreatic glucokinase in response to glucose and cAMP. J Cell Mol Med. 2009;13(8B):2386–95. Sporici R, Hodskins J, Locasto D, Meszaros L, Ferry A, Weidner A, et al. Repression of the prolactin promoter: a functional consequence of the heterodimerization between Pit-1 and Pit-1 β. J Mol Endocrinol. 2005;35(2):317–31. Tong Y, Zhou J, Mizutani J, Fukuoka H, Ren S-G, Gutierrez-Hartmann A, et al. CEBPD suppresses prolactin expression and prolactinoma cell proliferation. Mol Endocrinol. 2011;25(11):1880–91. Bouchon A, Facchetti F, Weigand MA, Colonna M. TREM-1 amplifies inflammation and is a crucial mediator of septic shock. Nature. 2001;410(6832):1103–7. Bouchon A, Hernández-Munain C, Cella M, Colonna M. A DAP12-mediated pathway regulates expression of CC chemokine receptor 7 and maturation of human dendritic cells. J Exp Med. 2001;194(8):1111–22. Jiang T, Zhang Y-D, Gao Q, Zhou J-S, Zhu X-C, Lu H, et al. TREM1 facilitates microglial phagocytosis of amyloid beta. Acta Neuropathol. 2016;132(5):667–83. Feng C-W, Chen N-F, Sung C-S, Kuo H-M, Yang S-N, Chen C-L, et al. Therapeutic effect of modulating TREM-1 via anti-inflammation and autophagy in Parkinson’s disease. Front Neurosci. 2019;13:769. Tammaro A, Derive M, Gibot S, Leemans JC, Florquin S, Dessing MC. TREM-1 and its potential ligands in non-infectious diseases: from biology to clinical perspectives. Pharmacol Ther. 2017;177:81–95. Thorsen SU, Pipper CB, Mortensen HB, Skogstrand K, Pociot F, Johannesen J, et al. Levels of soluble TREM‐1 in children with newly diagnosed type 1 diabetes and their siblings without type 1 diabetes: a Danish case-control study. Pediatr Diabetes. 2017;18(8):749–54. Subramanian S, Pallati PK, Sharma P, Agrawal DK, Nandipati KC. Significant association of TREM-1 with HMGB1, TLRs and RAGE in the pathogenesis of insulin resistance in obese diabetic populations. Am J Transl Res. 2017;9(7):3224. Aldrich A, Kielian T. Central nervous system fibrosis is associated with fibrocyte-like infiltrates. Am J Pathol. 2011;179(6):2952–62. Replogle JM, Chan G, White CC, Raj T, Winn PA, Evans DA, et al. A TREM 1 variant alters the accumulation of Alzheimer‐related amyloid pathology. Ann Neurol. 2015;77(3):469–77. Saadipour K. TREM1: a potential therapeutic target for Alzheimer’s disease. Neurotox Res. 2017;32(1):14–6. Lee J, Yee S-T, Kim J-J, Choi M-S, Kwon E-Y, Seo K-I, et al. Ursolic acid ameliorates thymic atrophy and hyperglycemia in streptozotocin-nicotinamide-induced diabetic mice. Chem Biol Interact. 2010;188(3):635–42. Gragnoli C, Reeves GM, Reazer J, Postolache TT. Dopamine-prolactin pathway potentially contributes to the schizophrenia and type 2 diabetes comorbidity. Transl Psychiatry. 2016;6(4):e785. Wu J, Zhou S-L, Pi L-H, Shi X-J, Ma L-R, Chen Z, et al. High glucose induces formation of tau hyperphosphorylation via Cav-1-mTOR pathway: a potential molecular mechanism for diabetes-induced cognitive dysfunction. Oncotarget. 2017;8(25):40843. Kickstein E, Krauss S, Thornhill P, Rutschow D, Zeller R, Sharkey J, et al. Biguanide metformin acts on tau phosphorylation via mTOR/protein phosphatase 2A (PP2A) signaling. Proc Natl Acad Sci U S A. 2010;107(50):21830–5. Jope RS, Johnson GV. The glamour and gloom of glycogen synthase kinase-3. Trends Biochem Sci. 2004;29(2):95–102. Tessarz AS, Cerwenka A. The TREM-1/DAP12 pathway. Immunol Lett. 2008;116(2):111–6. Saisho Y. Metformin and inflammation: its potential beyond glucose-lowering effect. Endocr Metab Immune Disord Drug Targets. 2015;15(3):196–205. Ekinci EI, Torkamani N, Ramchand SK, Churilov L, Sikaris KA, Lu ZX, et al. Higher maternal serum prolactin levels are associated with reduced glucose tolerance during pregnancy. J Diabetes Investig. 2017;8(5):697–700. Daimon M, Kamba A, Murakami H, Mizushiri S, Osonoi S, Yamaichi M, et al. Association between serum prolactin levels and insulin resistance in non-diabetic men. PLoS One. 2017;12(4):e0175204. Chen Y, Navratilova E, Dodick DW, Porreca F. An emerging role for prolactin in female-selective pain. Trends Neurosci. 2020;43(8):635–48. Banerjee RR, Cyphert HA, Walker EM, Chakravarthy H, Peiris H, Gu X, et al. Gestational diabetes mellitus from inactivation of prolactin receptor and MafB in islet β-cells. Diabetes. 2016;65(8):2331–41. Park JM, Jo SH, Kim MY, Kim TH, Ahn YH. Role of transcription factor acetylation in the regulation of metabolic homeostasis. Protein Cell. 2015;6(11):804–13. Park JM, Kim MY, Kim TH, Min DK, Yang GE, Ahn YH. Prolactin regulatory element-binding (PREB) protein regulates hepatic glucose homeostasis. Biochim Biophys Acta Mol Basis Dis. 2018;1864(6):2097–107. Bouckenooghe T, Sisino G, Aurientis S, Chinetti-Gbaguidi G, Kerr-Conte J, Staels B, et al. Adipose tissue macrophages (ATM) of obese patients are releasing increased levels of prolactin during an inflammatory challenge: a role for prolactin in diabesity? Biochim Biophys Acta. 2014;1842(4):584–93. Zhang B, Gaiteri C, Bodea L-G, Wang Z, McElwee J, Podtelezhnikov AA, et al. Integrated systems approach identifies genetic nodes and networks in late-onset Alzheimer’s disease. Cell. 2013;153(3):707–20. Liu Y-S, Yan W-J, Tan C-C, Li J-Q, Xu W, Cao X-P, et al. Common variant in TREM1 influencing brain amyloid deposition in mild cognitive impairment and Alzheimer’s disease. Neurotox Res. 2020;37(3):661–8. Sao T, Yoshino Y, Yamazaki K, Ozaki Y, Mori Y, Ochi S, et al. TREM1 mRNA expression in leukocytes and cognitive function in Japanese patients with Alzheimer’s disease. J Alzheimers Dis. 2018;64(4):1275–84. Melchior B, Garcia AE, Hsiung B-K, Lo KM, Doose JM, Thrash JC, et al. Dual induction of TREM2 and tolerance-related transcript, Tmem176b, in amyloid transgenic mice: implications for vaccine-based therapies for Alzheimer’s disease. ASN Neuro. 2010;2(3):e00037. Gaikwad S, Larionov S, Wang Y, Dannenberg H, Matozaki T, Monsonego A, et al. Signal regulatory protein-β1: a microglial modulator of phagocytosis in Alzheimer’s disease. Am J Pathol. 2009;175(6):2528–39. Li ZG, Zhang W, Sima AA. Alzheimer-like changes in rat models of spontaneous diabetes. Diabetes. 2007;56(7):1817–24. Pedersen WA, McMillan PJ, Kulstad JJ, Leverenz JB, Craft S, Haynatzki GR. Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice. Exp Neurol. 2006;199(2):265–73. De Felice FG, Vieira MN, Bomfim TR, Decker H, Velasco PT, Lambert MP, et al. Protection of synapses against Alzheimer’s-linked toxins: insulin signaling prevents the pathogenic binding of Aβ oligomers. Proc Natl Acad Sci U S A. 2009;106(6):1971–6. Kim B, Backus C, Oh S, Hayes JM, Feldman EL. Increased tau phosphorylation and cleavage in mouse models of type 1 and type 2 diabetes. Endocrinology. 2009;150(12):5294–301. Chen F, Dong RR, Zhong KL, Ghosh A, Tang SS, Long Y, et al. Antidiabetic drugs restore abnormal transport of amyloid-β across the blood-brain barrier and memory impairment in db/db mice. Neuropharmacology. 2016;101:123–36. Li J, Deng J, Sheng W, Zuo Z. Metformin attenuates Alzheimer’s disease-like neuropathology in obese, leptin-resistant mice. Pharmacol Biochem Behav. 2012;101(4):564–74. Barini E, Antico O, Zhao Y, Asta F, Tucci V, Catelani T, et al. Metformin promotes tau aggregation and exacerbates abnormal behavior in a mouse model of tauopathy. Mol Neurodegener. 2016;11(1):1–20. Picone P, Nuzzo D, Caruana L, Messina E, Barera A, Vasto S, et al. Metformin increases APP expression and processing via oxidative stress, mitochondrial dysfunction and NF-κB activation: use of insulin to attenuate metformin’s effect. Biochim Biophys Acta. 2015;1853(5):1046–59. Article / Publication Details

First-Page Preview

Abstract of Research Article

Received: July 07, 2021
Accepted: November 08, 2021
Published online: February 07, 2022

Number of Print Pages: 10
Number of Figures: 3
Number of Tables: 0

ISSN: 1021-7401 (Print)
eISSN: 1423-0216 (Online)

For additional information: https://www.karger.com/NIM

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