Detection of sex-specific glutamate changes in subregions of hippocampus in an early-stage Alzheimer's disease mouse model using GluCEST MRI.
1H‐MRS
APPNL‐F/NL‐F mice
Alzheimer's disease
GluCEST MRI
glutamate
sex‐specific changes
Journal
Alzheimer's & dementia : the journal of the Alzheimer's Association
ISSN: 1552-5279
Titre abrégé: Alzheimers Dement
Pays: United States
ID NLM: 101231978
Informations de publication
Date de publication:
11 Sep 2024
11 Sep 2024
Historique:
revised:
05
07
2024
received:
22
04
2024
accepted:
24
07
2024
medline:
12
9
2024
pubmed:
12
9
2024
entrez:
12
9
2024
Statut:
aheadofprint
Résumé
Regional glucose hypometabolism resulting in glutamate loss has been shown as one of the characteristics of Alzheimer's disease (AD). Because the impact of AD varies between the sexes, we utilized glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI) for high-resolution spatial mapping of cerebral glutamate and investigated subregional changes in a sex-specific manner. Eight-month-old male and female AD mice harboring mutant amyloid precursor protein (APP GluCEST measurements revealed significant (p ≤ 0.02) glutamate loss in the entorhinal cortex (% change ± standard error: 8.73 ± 2.12%), hippocampus (11.29 ± 2.41%), and hippocampal fimbriae (19.15 ± 2.95%) of male AD mice. A similar loss of hippocampal glutamate in male AD mice (11.22 ± 2.33%; p = 0.01) was also observed in GluCEST MRI detected glutamate reductions in the fimbria and entorhinal cortex of male AD mice, which was not reported previously. Resilience in female AD mice against these changes indicates an intact status of cerebral energy metabolism. Glutamate levels were monitored in different brain regions of early-stage Alzheimer's disease (AD) and wild-type male and female mice using glutamate-weighted chemical exchange saturation transfer (GluCEST) magnetic resonance imaging (MRI). Male AD mice exhibited significant glutamate loss in the hippocampus, entorhinal cortex, and the fimbriae of the hippocampus. Interestingly, female AD mice did not have any glutamate loss in any brain region and should be investigated further to find the probable cause. These findings demonstrate previously unreported sex-specific glutamate changes in hippocampal sub-regions using high-resolution GluCEST MRI.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : National Institute of Biomedical Imaging and Bioengineering of the NIH
ID : P41EB029460
Organisme : National Institute on Aging of the NIH
ID : R01AG071725
Organisme : National Institute on Aging of the NIH
ID : R01AG063869
Organisme : Abramson Cancer Center Support Grant
ID : P30CA016520
Organisme : NIH Shared Instrumentation Grant
ID : S10OD023465-01A1
Organisme : Penn Vet Institute for Infectious & Zoonotic Diseases Core pilot grant opportunity 2022
Informations de copyright
© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.
Références
WHO. Global action plan on the public health response to dementia 2017‐2025. 2017.
2023 Alzheimer's disease facts and figures. Alzheimers Dement. 2023;19(4):1598‐1695. doi:10.1002/alz.13016
Erecinska M, Silver IA. Metabolism and role of glutamate in mammalian brain. Prog Neurobiol. 1990;35(4):245‐296. doi:10.1016/0301‐0082(90)90013‐7
Pal MM. Glutamate: the master neurotransmitter and its implications in chronic stress and mood disorders. Front Hum Neurosci. 2021;15:722323. doi:10.3389/fnhum.2021.722323
Morris RG, Anderson E, Lynch GS, Baudry M. Selective impairment of learning and blockade of long‐term potentiation by an N‐methyl‐D‐aspartate receptor antagonist, AP5. Nature. 1986;319(6056):774‐776. doi:10.1038/319774a0
Bliss TV, Collingridge GL. A synaptic model of memory: long‐term potentiation in the hippocampus. Nature. 1993;361(6407):31‐39. doi:10.1038/361031a0
Chen SQ, Cai Q, Shen YY, et al. Age‐related changes in brain metabolites and cognitive function in APP/PS1 transgenic mice. Behav Brain Res. 2012;235(1):1‐6. doi:10.1016/j.bbr.2012.07.016
Patel AB, Tiwari V, Veeraiah P, Saba K. Increased astroglial activity and reduced neuronal function across brain in AβPP‐PS1 mouse model of Alzheimer's disease. J Cereb Blood Flow Metab. 2018;38(7):1213‐1226. doi:10.1177/0271678×17709463
Wang H, Tan L, Wang HF, et al. Magnetic resonance spectroscopy in Alzheimer's disease: systematic review and meta‐analysis. J Alzheimers Dis. 2015;46(4):1049‐1070. doi:10.3233/JAD‐143225
Walecki J, Barcikowska M, Cwikla JB, Gabryelewicz T. N‐acetylaspartate, choline, myoinositol, glutamine and glutamate (glx) concentration changes in proton MR spectroscopy (1H MRS) in patients with mild cognitive impairment (MCI). Med Sci Monit. 2011;17(12):MT105‐111. doi:10.12659/msm.882112
Joe E, Medina LD, Ringman JM, O'Neill J. 1H MRS spectroscopy in preclinical autosomal dominant Alzheimer disease. Brain Imaging Behav. 2019;13(4):925‐932. doi:10.1007/s11682‐018‐9913‐1
Nilsen LH, Witter MP, Sonnewald U. Neuronal and astrocytic metabolism in a transgenic rat model of Alzheimer's disease. J Cereb Blood Flow Metab. 2014;34(5):906‐914. doi:10.1038/jcbfm.2014.37
de Leon MJ, Ferris SH, George AE, et al. Positron emission tomographic studies of aging and Alzheimer disease. AJNR Am J Neuroradiol. 1983;4(3):568‐571.
Soni ND, Ramesh A, Roy D, Patel AB. Brain energy metabolism in intracerebroventricularly administered streptozotocin mouse model of Alzheimer's disease: a 1H‐[13C]‐NMR study. J Cereb Blood Flow Metab. 2021;41(9):2344‐2355. doi:10.1177/0271678×21996176
Tiwari V, Patel AB. Impaired glutamatergic and GABAergic function at early age in AβPPswe‐PS1dE9 mice: implications for Alzheimer's disease. J Alzheimers Dis. 2012;28(4):765‐769. doi:10.3233/JAD‐2011‐111502
Mason GF, Rothman DL, Behar KL, Shulman RG. NMR determination of the TCA cycle rate and alpha‐ketoglutarate/glutamate exchange rate in rat brain. J Cereb Blood Flow Metab. 1992;12(3):434‐447. doi:10.1038/jcbfm.1992.61
Crescenzi R, DeBrosse C, Nanga RP, et al. In vivo measurement of glutamate loss is associated with synapse loss in a mouse model of tauopathy. Neuroimage. 2014;101:185‐192. doi:10.1016/j.neuroimage.2014.06.067
Cai K, Haris M, Singh A, et al. Magnetic resonance imaging of glutamate. Nat Med. 2012;18(2):302‐306. doi:10.1038/nm.2615
Cember ATJ, Nanga RPR, Reddy R. Glutamate‐weighted CEST (gluCEST) imaging for mapping neurometabolism: an update on the state of the art and emerging findings from in vivo applications. NMR Biomed. 2023;36(6):e4780. doi:10.1002/nbm.4780
Podcasy JL, Epperson CN. Considering sex and gender in Alzheimer disease and other dementias. Dialogues Clin Neurosci. 2016;18(4):437‐446.
Alzheimer's A. 2020 Alzheimer's disease facts and figures. Alzheimers Dement. 2020;16:391‐460. doi:10.1002/alz.12068
Ngun TC, Ghahramani N, Sanchez FJ, Bocklandt S, Vilain E. The genetics of sex differences in brain and behavior. Front Neuroendocrinol. 2011;32(2):227‐246. doi:10.1016/j.yfrne.2010.10.001
de Vries GJ, Sodersten P. Sex differences in the brain: the relation between structure and function. Horm Behav. 2009;55(5):589‐596. doi:10.1016/j.yhbeh.2009.03.012
Cahill L. Why sex matters for neuroscience. Nat Rev Neurosci. 2006;7(6):477‐484. doi:10.1038/nrn1909
Andrew MK, Tierney MC. The puzzle of sex, gender and Alzheimer's disease: why are women more often affected than men? Women's Health. 2018;14:1745506518817995.
Zakiniaeiz Y, Cosgrove KP, Potenza MN, Mazure CM. Balance of the sexes: addressing sex differences in preclinical research. Yale J Biol Med. 2016;89(2):255‐259.
Zucker I, Beery AK. Males still dominate animal studies. Nature. 2010;465(7299):690. doi:10.1038/465690a
Plevkova J, Brozmanova M, Harsanyiova J, Sterusky M, Honetschlager J, Buday T. Various aspects of sex and gender bias in biomedical research. Physiol Res. 2020;69(Suppl 3):S367‐S378. doi:10.33549/physiolres.934593
Beery AK, Zucker I. Sex bias in neuroscience and biomedical research. Neurosci Biobehav Rev. 2011;35(3):565‐572. doi:10.1016/j.neubiorev.2010.07.002
Jack CR, Jr, Bennett DA, Blennow K, et al. NIA‐AA Research framework: toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535‐562. doi:10.1016/j.jalz.2018.02.018
Zhang J, Wu N, Wang S, et al. Neuronal loss and microgliosis are restricted to the core of Abeta deposits in mouse models of Alzheimer's disease. Aging Cell. 2021;20(6):e13380. doi:10.1111/acel.13380
Saito T, Matsuba Y, Mihira N, et al. Single app knock‐in mouse models of Alzheimer's disease. Nat Neurosci. 2014;17(5):661‐663. doi:10.1038/nn.3697
Tarrant JC, Binder ZA, Bugatti M, et al. Pathology of macrophage activation syndrome in humanized NSGS mice. Res Vet Sci. 2021;134:137‐146. doi:10.1016/j.rvsc.2020.12.003
Swain A, Soni ND, Wilson N, et al. Early‐stage mapping of macromolecular content in APP(NL‐F) mouse model of Alzheimer's disease using nuclear Overhauser effect MRI. Front Aging Neurosci. 2023;15:1266859. doi:10.3389/fnagi.2023.1266859
Dorr AE, Lerch JP, Spring S, Kabani N, Henkelman RM. High resolution three‐dimensional brain atlas using an average magnetic resonance image of 40 adult C57Bl/6J mice. Neuroimage. 2008;42(1):60‐69. doi:10.1016/j.neuroimage.2008.03.037
Vercauteren T, Pennec X, Perchant A, Ayache N. Diffeomorphic demons: efficient non‐parametric image registration. Neuroimage. 2009;45(1 Suppl):S61‐72. doi:10.1016/j.neuroimage.2008.10.040
Provencher SW. Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med. 1993;30(6):672‐679. doi:10.1002/mrm.1910300604
Ito I, Sugiyama H. Roles of glutamate receptors in long‐term potentiation at hippocampal mossy fiber synapses. Neuroreport. 1991;2(6):333‐336. doi:10.1097/00001756‐199106000‐00008
Dahmani L, Courcot B, Near J, et al. Fimbria‐Fornix volume is associated with spatial memory and olfactory identification in humans. Front Syst Neurosci. 2019;13:87. doi:10.3389/fnsys.2019.00087
Garcia AD, Buffalo EA. Anatomy and function of the primate entorhinal cortex. Annu Rev Vis Sci. 2020;6:411‐432. doi:10.1146/annurev‐vision‐030320‐041115
Igarashi KM. Entorhinal cortex dysfunction in Alzheimer's disease. Trends Neurosci. 2023;46(2):124‐136. doi:10.1016/j.tins.2022.11.006
Jack CR Jr, Petersen RC, Xu Y, et al. Rates of hippocampal atrophy correlate with change in clinical status in aging and AD. Neurology. 2000;55(4):484‐489. doi:10.1212/wnl.55.4.484
Masuda A, Kobayashi Y, Kogo N, Saito T, Saido TC, Itohara S. Cognitive deficits in single app knock‐in mouse models. Neurobiol Learn Mem. 2016;135:73‐82. doi:10.1016/j.nlm.2016.07.001
Brophy PJ. Axoglial junctions: separate the channels or scramble the message. Curr Biol. 2001;11(14):R555‐557. doi:10.1016/s0960‐9822(01)00341‐4
Fields RD. A new mechanism of nervous system plasticity: activity‐dependent myelination. Nat Rev Neurosci. 2015;16(12):756‐767. doi:10.1038/nrn4023
Wake H, Ortiz FC, Woo DH, Lee PR, Angulo MC, Fields RD. Nonsynaptic junctions on myelinating glia promote preferential myelination of electrically active axons. Nat Commun. 2015;6:7844. doi:10.1038/ncomms8844
Lee DW, Heo H, Woo CW, et al. Temporal changes in in vivo glutamate signal during demyelination and remyelination in the corpus callosum: a glutamate‐weighted chemical exchange saturation transfer imaging study. Int J Mol Sci. 2020;21(24):9468. doi:10.3390/ijms21249468
Moini J, Pirouz P. Chapter 6: Cerebral cortex. Functional and clinical neuroanatomy: a guide for health care professionals. Academic Press; 2020:177‐240. doi:10.1016/B978-0-12-817424-1.00006-9
Cheng LL, Newell K, Mallory AE, Hyman BT, Gonzalez RG. Quantification of neurons in Alzheimer and control brains with ex vivo high resolution magic angle spinning proton magnetic resonance spectroscopy and stereology. Magn Reson Imaging. 2002;20(7):527‐533. doi:10.1016/s0730‐725x(02)00512‐x
Chen HR, DeGrauw T, Kuan CY. (Phospho)creatine: the reserve and merry‐go‐round of brain energetics. Neural Regen Res. 2023;18(2):327‐328. doi:10.4103/1673‐5374.346470
Burklen TS, Schlattner U, Homayouni R, et al. The creatine kinase/creatine connection to Alzheimer's disease: CK‐inactivation, APP‐CK complexes and focal creatine deposits. J Biomed Biotechnol. 2006;2006(3):35936. doi:10.1155/JBB/2006/35936
Li H, Tang Z, Chu P, et al. Neuroprotective effect of phosphocreatine on oxidative stress and mitochondrial dysfunction induced apoptosis in vitro and in vivo: involvement of dual PI3K/Akt and Nrf2/HO‐1 pathways. Free Radic Biol Med. 2018;120:228‐238. doi:10.1016/j.freeradbiomed.2018.03.014
David S, Shoemaker M, Haley BE. Abnormal properties of creatine kinase in Alzheimer's disease brain: correlation of reduced enzyme activity and active site photolabeling with aberrant cytosol‐membrane partitioning. Brain Res Mol Brain Res. 1998;54(2):276‐287. doi:10.1016/s0169‐328x(97)00343‐4
Pettegrew JW, Panchalingam K, Klunk WE, McClure RJ, Muenz LR. Alterations of cerebral metabolism in probable Alzheimer's disease: a preliminary study. Neurobiol Aging. 1994;15(1):117‐132. doi:10.1016/0197‐4580(94)90152‐x
Smith RN, Agharkar AS, Gonzales EB. A review of creatine supplementation in age‐related diseases: more than a supplement for athletes. F1000Res. 2014;3:222. doi:10.12688/f1000research.5218.1
Souza MA, Magni DV, Guerra GP, et al. Involvement of hippocampal CAMKII/CREB signaling in the spatial memory retention induced by creatine. Amino Acids. 2012;43(6):2491‐2503. doi:10.1007/s00726‐012‐1329‐4
Avgerinos KI, Spyrou N, Bougioukas KI, Kapogiannis D. Effects of creatine supplementation on cognitive function of healthy individuals: a systematic review of randomized controlled trials. Exp Gerontol. 2018;108:166‐173. doi:10.1016/j.exger.2018.04.013
Schaffer S, Kim HW. Effects and mechanisms of taurine as a therapeutic agent. Biomol Ther (Seoul). 2018;26(3):225‐241. doi:10.4062/biomolther.2017.251
Jakaria M, Azam S, Haque ME, et al. Taurine and its analogs in neurological disorders: focus on therapeutic potential and molecular mechanisms. Redox Biol. 2019;24:101223. doi:10.1016/j.redox.2019.101223
Oh SJ, Lee HJ, Jeong YJ, et al. Evaluation of the neuroprotective effect of taurine in Alzheimer's disease using functional molecular imaging. Sci Rep. 2020;10(1):15551. doi:10.1038/s41598‐020‐72755‐4
Arai H, Kobayashi K, Ichimiya Y, Kosaka K, Iizuka R. A preliminary study of free amino acids in the postmortem temporal cortex from Alzheimer‐type dementia patients. Neurobiol Aging. 1984;5(4):319‐321. doi:10.1016/0197‐4580(84)90009‐5
Carroll JC, Rosario ER, Kreimer S, et al. Sex differences in beta‐amyloid accumulation in 3xTg‐AD mice: role of neonatal sex steroid hormone exposure. Brain Res. 2010;1366:233‐245. doi:10.1016/j.brainres.2010.10.009
Hu YT, Chen XL, Zhang YN, et al. Sex differences in hippocampal beta‐amyloid accumulation in the triple‐transgenic mouse model of Alzheimer's disease and the potential role of local estrogens. Front Neurosci. 2023;17:1117584. doi:10.3389/fnins.2023.1117584
Thal DR, Del Tredici K, Ludolph AC, et al. Stages of granulovacuolar degeneration: their relation to Alzheimer's disease and chronic stress response. Acta Neuropathol. 2011;122(5):577‐589. doi:10.1007/s00401‐011‐0871‐6
Atamna H, Boyle K. Amyloid‐beta peptide binds with heme to form a peroxidase: relationship to the cytopathologies of Alzheimer's disease. Proc Natl Acad Sci USA. 2006;103(9):3381‐3386. doi:10.1073/pnas.0600134103
Lloret A, Badia MC, Mora NJ, et al. Gender and age‐dependent differences in the mitochondrial apoptogenic pathway in Alzheimer's disease. Free Radic Biol Med. 2008;44(12):2019‐2025. doi:10.1016/j.freeradbiomed.2008.02.017
Vina J, Lloret A. Why women have more Alzheimer's disease than men: gender and mitochondrial toxicity of amyloid‐beta peptide. J Alzheimers Dis. 2010;20(Suppl 2):S527‐533. doi:10.3233/JAD‐2010‐100501
Finch CE. The menopause and aging, a comparative perspective. J Steroid Biochem Mol Biol. 2014;142:132‐141. doi:10.1016/j.jsbmb.2013.03.010
Diaz Brinton R. Minireview: translational animal models of human menopause: challenges and emerging opportunities. Endocrinology. 2012;153(8):3571‐3578. doi:10.1210/en.2012‐1340
Mosconi L, Berti V, Quinn C, et al. Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery. PLoS One. 2017;12(10):e0185926. doi:10.1371/journal.pone.0185926
Brinton RD, Yao J, Yin F, Mack WJ, Cadenas E. Perimenopause as a neurological transition state. Nat Rev Endocrinol. 2015;11(7):393‐405. doi:10.1038/nrendo.2015.82
Shughrue PJ, Lane MV, Merchenthaler I. Comparative distribution of estrogen receptor‐alpha and ‐beta mRNA in the rat central nervous system. J Comp Neurol. 1997;388(4):507‐525. doi:10.1002/(sici)1096‐9861(19971201)388:4<507::aid‐cne1>3.0.co;2‐6
McEwen BS, Akama KT, Spencer‐Segal JL, Milner TA, Waters EM. Estrogen effects on the brain: actions beyond the hypothalamus via novel mechanisms. Behav Neurosci. 2012;126(1):4‐16. doi:10.1037/a0026708
Yin F, Yao J, Sancheti H, et al. The perimenopausal aging transition in the female rat brain: decline in bioenergetic systems and synaptic plasticity. Neurobiol Aging. 2015;36(7):2282‐2295. doi:10.1016/j.neurobiolaging.2015.03.013
Yao J, Irwin R, Chen S, Hamilton R, Cadenas E, Brinton RD. Ovarian hormone loss induces bioenergetic deficits and mitochondrial beta‐amyloid. Neurobiol Aging. 2012;33(8):1507‐1521. doi:10.1016/j.neurobiolaging.2011.03.001
Ding F, Yao J, Rettberg JR, Chen S, Brinton RD. Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention. PLoS One. 2013;8(11):e79977. doi:10.1371/journal.pone.0079977
Maki PM, Resnick SM. Longitudinal effects of estrogen replacement therapy on PET cerebral blood flow and cognition. Neurobiol Aging. 2000;21(2):373‐383. doi:10.1016/s0197‐4580(00)00123‐8
Rasgon NL, Silverman D, Siddarth P, et al. Estrogen use and brain metabolic change in postmenopausal women. Neurobiol Aging. 2005;26(2):229‐235. doi:10.1016/j.neurobiolaging.2004.03.003
Rasgon NL, Geist CL, Kenna HA, Wroolie TE, Williams KE, Silverman DH. Prospective randomized trial to assess effects of continuing hormone therapy on cerebral function in postmenopausal women at risk for dementia. PLoS One. 2014;9(3):e89095. doi:10.1371/journal.pone.0089095