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ORIGINAL RESEARCH

Neuroprotective Effects of Leptin on the APP/PS1 Alzheimer’s Disease Mouse Model: Role of Microglial and Neuroinflammation

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Pages 69-79 | Received 21 Jul 2023, Accepted 05 Oct 2023, Published online: 25 Oct 2023

References

  • Scheltens P, De Strooper B, Kivipelto M, et al. Alzheimer’s disease. Lancet. 2021;397:1577–1590. doi:10.1016/S0140-6736(20)32205-4
  • Serrano-Pozo A, Frosch MP, Masliah E, Hyman BT. Neuropathological alterations in Alzheimer disease. Cold Spring Harb Perspect Med. 2011;1:a006189–a006189. doi:10.1101/cshperspect.a006189
  • Xu W, Tan L, Wang HF, et al. Meta-analysis of modifiable risk factors for Alzheimer’s disease. J Neurol. 2015;86:1299–1306.
  • Lawson LJ, Perry VH, Dri P, Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience. 1990;39:151–170. doi:10.1016/0306-4522(90)90229-W
  • Colton CA. Heterogeneity of microglial activation in the innate immune response in the brain. J Neuroimmune Pharmacol. 2009;4:399–418. doi:10.1007/s11481-009-9164-4
  • Hanisch UK, Kettenmann H. Microglia: active sensor and versatile effector cells in the normal and pathologic brain. Nature Neuroscience. 2007;10:1387–1394. doi:10.1038/nn1997
  • Salter MW, Beggs S. Sublime microglia: expanding roles for The Guardians of the CNS. Cell. 2014;158:15–24. doi:10.1016/j.cell.2014.06.008
  • Wendimu MY, Hooks SB. Microglia phenotypes in aging and neurodegenerative diseases. Cells. 2022;11:2091. doi:10.3390/cells11132091
  • Tcw J, Qian L, Pipalia NH, et al. Cholesterol and matrisome pathways dysregulated in astrocytes and microglia. Cell. 2022;185:2213–2233.e2225. doi:10.1016/j.cell.2022.05.017
  • Wang S, Sudan R, Peng V, et al. TREM2 drives microglia response to amyloid-β via SYK-dependent and -independent pathways. Cell. 2022;185:4153–4169.e4119. doi:10.1016/j.cell.2022.09.033
  • Lopes KP, Snijders GJL, Humphrey J, et al. Genetic analysis of the human microglial transcriptome across brain regions, aging and disease pathologies. Nat Genet. 2022;54:4–17. doi:10.1038/s41588-021-00976-y
  • Li Y, Li Z, Yang M, et al. Decoding the temporal and regional specification of microglia in the developing human brain. Cell Stem Cell. 2022;29:e626. doi:10.1016/j.stem.2022.02.004
  • Ennerfelt H, Frost EL, Shapiro DA, et al. SYK coordinates neuroprotective microglial responses in neurodegenerative disease. Cell. 2022;185:e4122. doi:10.1016/j.cell.2022.09.030
  • Schafer DP, Lehrman E, Kautzman A, et al. Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012;74:691–705. doi:10.1016/j.neuron.2012.03.026
  • Herz J, Filiano AJ, Wiltbank AT, Yogev N, Kipnis J. Myeloid cells in the central nervous system. Immunity. 2017;46:943–956. doi:10.1016/j.immuni.2017.06.007
  • Parkhurst CN, Yang G, Ninan I, et al. Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell. 2013;155:1596–1609. doi:10.1016/j.cell.2013.11.030
  • Madinier A, Bertrand N, Mossiat C, et al. Microglial involvement in neuroplastic changes following focal brain ischemia in rats. PLoS One. 2009;4:e8101. doi:10.1371/journal.pone.0008101
  • Lue LF, Kuo YM, Beach T, Walker DG. Microglia activation and anti-inflammatory regulation in Alzheimer’s disease. Molecular Neurobiol. 2010;41:115–128. doi:10.1007/s12035-010-8106-8
  • Leyns CEG, Holtzman DM. Glial contributions to neurodegeneration in tauopathies. Molecular Neurodeg. 2017;12:50. doi:10.1186/s13024-017-0192-x
  • Shippy DC, Ulland TK. Microglial immunometabolism in Alzheimer’s disease. Front Cell Neurosci. 2020;14:563446. doi:10.3389/fncel.2020.563446
  • Zhang Y, Proenca R, Maffei M, et al. Positional cloning of the mouse obese gene and its human homologue. Nature. 1994;372:425–432. doi:10.1038/372425a0
  • Stephens TW, Basinski M, Bristow PK, et al. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature. 1995;377:530–532. doi:10.1038/377530a0
  • Huang XF, Koutcherov I, Lin S, Wang HQ, Storlien L. Localization of leptin receptor mRNA expression in mouse brain. Neuroreport. 1996;7:2635–2638. doi:10.1097/00001756-199611040-00045
  • Tartaglia LA, Dembski M, Weng X, et al. Identification and expression cloning of a leptin receptor, OB-R. Cell. 1995;83:1263–1271. doi:10.1016/0092-8674(95)90151-5
  • McGregor G, Clements L, Farah A, Irving AJ, Harvey J. Age-dependent regulation of excitatory synaptic transmission at hippocampal temporoammonic-CA1 synapses by leptin. Neurobiology of Aging. 2018;69:76–93. doi:10.1016/j.neurobiolaging.2018.05.007
  • Lilamand M, Bouaziz-Amar E, Dumurgier J, et al. Plasma leptin is associated with amyloid CSF biomarkers and Alzheimer’s disease diagnosis in cognitively impaired patients. The J Gerontol. 2023;78 645–652.
  • Ha J, Kwak S, Kim KY, et al. Relationship between adipokines, cognition, and brain structures in old age depending on obesity. J Gerontol. 2022.
  • Hamilton K, Harvey J. The neuronal actions of leptin and the implications for treating Alzheimer’s disease. Pharmaceuticals. 2021;14:1.
  • Hamilton K, Harvey J. Leptin regulation of hippocampal synaptic function in health and disease. Vitam Hormon. 2021;115:105–127.
  • King A, Brain A, Hanson K, et al. Disruption of leptin signalling in a mouse model of Alzheimer’s disease. Meta Brain Dis. 2018;33. doi:10.1007/s11011-018-0203-9
  • Fewlass DC, Noboa K, Pi‐Sunyer FX, et al. Obesity-related leptin regulates Alzheimer’s Abeta. FASEB J. 2004;18:1870–1878. doi:10.1096/fj.04-2572com
  • Shinjyo N, Kita K. Infection and immunometabolism in the central nervous system: a possible mechanistic link between metabolic imbalance and dementia. Front Cell Neurosci. 2021;15:765217.
  • Tang CH, Lu D-Y, Yang R-S, et al. Leptin-induced IL-6 production is mediated by leptin receptor, insulin receptor substrate-1, phosphatidylinositol 3-kinase, Akt, NF-kappaB, and p300 pathway in microglia. J Immunol. 2007;179:1292–1302. doi:10.4049/jimmunol.179.2.1292
  • Pinteaux E, Inoue W, Schmidt L, et al. Leptin induces interleukin-1beta release from rat microglial cells through a caspase 1 independent mechanism. J Neurochem. 2007;102:826–833. doi:10.1111/j.1471-4159.2007.04559.x
  • Chang KT, Lin Y-L, Lin C-T, et al. Leptin is essential for microglial activation and neuropathic pain after preganglionic cervical root avulsion. Life Sci. 2017;187:31–41. doi:10.1016/j.lfs.2017.08.016
  • Benbenishty A, Schneiderman J, Mongin AA. Intraarterial anti-leptin therapy via ICA protects ipsilateral CA1 neurons subjected to ischemia and reperfusion. PLoS One. 2022;17:e0261644. doi:10.1371/journal.pone.0261644
  • Lu L, Fu Z, Wu B, Zhang D, Wang Y. Leptin ameliorates Abeta1-42-induced Alzheimer’s disease by suppressing inflammation via activating p-Akt signaling pathway. Transl Neurosci. 2023;14. doi:10.1515/tnsci-2022-0270
  • Calió ML, Mosini AC, Marinho DS, et al. Leptin enhances adult neurogenesis and reduces pathological features in a transgenic mouse model of Alzheimer’s disease. Neurobiol Dis. 2021;148:105219. doi:10.1016/j.nbd.2020.105219
  • Fernandez-Martos CM, Gonzalez P, Rodriguez FJ, Combs C. Acute leptin treatment enhances functional recovery after spinal cord injury. PLoS One. 2012;7:e35594. doi:10.1371/journal.pone.0035594
  • Davis BM, Salinas-Navarro M, Cordeiro MF, Moons L, De Groef L. Characterizing microglia activation: a spatial statistics approach to maximize information extraction. Sci Rep. 2017;7. doi:10.1038/s41598-017-01747-8
  • Pérez-González R, Alvira-Botero MX, Robayo O, et al. Leptin gene therapy attenuates neuronal damages evoked by amyloid-β and rescues memory deficits in APP/PS1 mice. Gene Therapy. 2014;21:298–308. doi:10.1038/gt.2013.85
  • Babcock AA, Ilkjær L, Clausen BH, et al. Cytokine-producing microglia have an altered beta-amyloid load in aged APP/PS1 Tg mice. Brain Behav Immunit. 2015;48:86–101. doi:10.1016/j.bbi.2015.03.006
  • Bonda DJ, Stone JG, Torres SL, et al. Dysregulation of leptin signaling in Alzheimer disease: evidence for neuronal leptin resistance. J Neurochemist. 2014;128:162–172. doi:10.1111/jnc.12380
  • Takemiya T, Fumizawa K, Yamagata K, Iwakura Y, Kawakami M. Brain interleukin-1 facilitates learning of a water maze spatial memory task in young mice. Front Behav Neurosci. 2017;11. doi:10.3389/fnbeh.2017.00202
  • Del Rey A, Balschun D, Wetzel W, Randolf A, Besedovsky HO. A cytokine network involving brain-borne IL-1beta, IL-1ra, IL-18, IL-6, and TNFalpha operates during long-term potentiation and learning. Brain Behav Immu. 2013;33:15–23. doi:10.1016/j.bbi.2013.05.011
  • Balschun D, Wetzel W, Rey A, et al. Interleukin-6: a cytokine to forget. FASEB J. 2004;18:1788–1790. doi:10.1096/fj.04-1625fje
  • Jankowsky JL, Derrick BE, Patterson PH. Cytokine responses to LTP induction in the rat hippocampus: a comparison of in vitro and in vivo techniques. Learn Mem. 2000;7:400–412. doi:10.1101/lm.32600
  • Ma J, Zhang W, Wang H-F, et al. Peripheral blood adipokines and insulin levels in patients with Alzheimer’s disease: a replication study and meta-analysis. Current Alzheimer Res. 2016;13:223–233. doi:10.2174/156720501303160217111434
  • Lieb W, Beiser AS, Vasan RS, et al. Association of plasma leptin levels with incident Alzheimer disease and MRI measures of brain aging. JAMA. 2009;302:2565. doi:10.1001/jama.2009.1836
  • Campfield LA, Smith FJ, Burn P. The OB protein (leptin) pathway--a link between adipose tissue mass and central neural networks. Horm Metab Res. 1996;28:619–632. doi:10.1055/s-2007-979867
  • Greco SJ, Bryan KJ, Sarkar S, et al. Leptin reduces pathology and improves memory in a transgenic mouse model of Alzheimer’s disease. J Alzheimer’s Dis. 2010;19:1155–1167.
  • Casado ME, Collado-Perez R, Frago LM, Barrios V. Recent advances in the knowledge of the mechanisms of leptin physiology and actions in neurological and metabolic pathologies. Inter J Molec Sci. 2023;24:1.
  • Bivona G, Iemmolo M, Agnello L, et al. Microglial activation and priming in Alzheimer’s disease: state of the art and future perspectives. Inter J Mole Sci. 2023;24:884. doi:10.3390/ijms24010884
  • Michaud JP, Hallé M, Lampron A, et al. Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer’s disease-related pathology. Proceed National Acad Sci Unit State Am. 2013;110:1941–1946. doi:10.1073/pnas.1215165110
  • Merighi S, Nigro M, Travagli A, Gessi S. Microglia and Alzheimer’s disease. Inter J Molec Sci. 2022;23:12990. doi:10.3390/ijms232112990
  • McKee CG, Hoffos M, Vecchiarelli HA, Tremblay ME. Microglia: a pharmacological target for the treatment of age-related cognitive decline and Alzheimer’s disease. Front Pharmacol. 2023;14. doi:10.3389/fphar.2023.1125982
  • Bagheri-Mohammadi S. Microglia in Alzheimer’s disease: the role of stem cell-microglia interaction in brain homeostasis. Neurochem Res. 2021;46:141–148. doi:10.1007/s11064-020-03162-4
  • Wu YG, Song LJ, Yin LJ, et al. The effects and potential of microglial polarization and crosstalk with other cells of the central nervous system in the treatment of Alzheimer’s disease. Neural Regen Res. 2023;18:947–954.