Abstract
Background
Autophagy is a specific universal biological phenomenon in eukaryotic cells, which is characterized by cytoplasmic vacuoles in the process of degrading cellular contents in lysosomes. The hippocampus plays an important role in higher nervous activities such as emotional integration, cognition, and memory. As an area closely related to learning and memory functions of the brain, the hippocampus is particularly sensitive to injuries caused by various reasons.
Purpose
Autophagy has certain links with a variety of causes of hippocampal neuronal injury. This short review discusses and summarizes this correlation with a focus on the possible role of autophagy and mechanisms in it.
Conclusion
The current correlation between autophagy and hippocampal neuronal injury has not been completely determined by the general public alike. Further studies are needed to determine special effects of autophagy on hippocampal neuronal injury, which might accelerate the development of therapeutic interventions in hippocampal neuronal injury in many neurological disorders.
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References
Kroemer G, Mariño G, Levine B (2010) Autophagy and the integrated stress response. Mol Cell 40(2):280–293
Mazure NM, Pouysségur J (2010) Hypoxia-induced autophagy: cell death or cell survival? Curr Opin Cell Biol 22(2):177–180
Mortimore GE, Poso AR (1987) Intracellular protein catabolism and its control during nutrient deprivation and supply. Annu Rev Nutr 7:539–564
Klionsky DJ, Emr SD (2000) Autophagy as a regulated pathway of cellular degradation. Science 290(5497):1717–1721
Crotzer VL, Blum JS (2005) Autophagy and intracellular surveillance: modulating MHC class II antigen presentation with stress. Proc Natl Acad Sci U S A 102(22):7779–7780
Reggiori F, klionsky DJ (2002) Autophagy in the eukaryotic cell. Eukaryot Cell 1(1):11–21
Mizushima N, Yoshimori T, Levine B (2010) Methods in mammalian autophagy research. Cell 140(3):313–326
Martinet W, De Meyer GR, Andries L, Herman AG, Kockx MM (2006) In Situ Detection of Starvation-induced Autophagy. J Histochem Cytochem 54(1):85–96
Biederbick A, kem HF, Elsasser HP (1995) Monodansylcadaverine (MDC) is a specific in vivo marker for autophagic vacuoles. Eur J Cell Biol 66(1):3–14
Baronio D, Martinez D, Fiori CZ, Bambini-Junior V, Forgiarini LF, Pase da Rosa D, Kim LJ, Cerski MR (2013) Altered aquaporins in the brains of mice submitted to intermittent hypoxia model of sleep apnea. Respir Physiol Neurobiol 185(2):217–221
Lieberthal W (2008) Macroautophagy: a mechanism for mediating cell death or for promoting cell survival? Kidney Int 74(5):555–557
Kundu M, Thompson CB (2008) Autophagy: basic principles and relevance to disease. Annu Rev Pathol 3:427–455
Klionsky DJ (2005) The molecular machinery of autophagy: unanswered questions. J Cell Sci 118(Pt 1):7–18
Mizushima N (2007) Autophagy: process and function. Genes Dev 21(22):2861–2873
Nixon RA, Wegiel J, Kumar A, Yu WH, Peterhoff C, Cataldo A, Cuervo AM (2005) Extensive involvement of autophagy in Alzheimer disease: an immuno-electron microscopy study. J Neuropathol Exp Neurol 64(2):113–122
Nixon RA, Yang DS (2012) Autophagy and neuronal cell death in neurological disorders. Cold Spring Harb Perspect Biol. doi:10.1101/cshperspect.a008839
Sanchez-Varo R, Trujillo-Estrada L, Sanchez-Mejias E, Torres M, Baglietto-Vargas D, Moreno-Gonzalez I, De Castro V, Jimenez S, Ruano D, Vizuete M, Davila JC, Garcia-Verdugo JM, Jimenez AJ, Vitorica J, Gutierrez A (2012) Abnormal accumulation of autophagic vesicles correlates with axonal and synaptic pathology in young Alzheimer’s mice hippocampus. Acta Neuropathol 123(1):53–70
Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441(7095):885–889
Caccamo A, Majumder S, Richardson A, Strong R, Oddo S (2010) Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J Biol Chem 285(17):13107–13120
Pimplikar SW, Nixon RA, Robakis NK, Shen J, Tsai LH (2010) Amyloid-independent mechanisms in Alzheimer’s disease pathogenesis. J Neurosci 30(45):14946–14954
Nixon RA, Yang DS (2011) Autophagy failure in Alzheimer’s disease—locating the primary defect. Neurobiol Dis 43(1):38–45
Pickford F, Masliah E, Britschgi M, Lucin K, Narasimhan R, Jaeger PA, Small S, Spencer B, Rockenstein E, Levine B, Wyss-Coray T (2008) The autophagy-related protein beclin 1 shows reduced expression in early Alzheimer disease and regulates amyloid beta accumulation in mice. J Clin Invest 118(6):2190–2199
Yang DS, Stavrides P, Mohan PS, Kaushik S, Kumar A, Ohno M, Schmidt SD, Wesson D, Bandyopadhyay U, Jiang Y, Pawlik M, Peterhoff CM, Yang AJ, Wilson DA, St George-Hyslop P, Westaway D, Mathews PM, Levy E, Cuervo AM, Nixon RA (2011) Reversal of autophagy dysfunction in the TgCRND8 mouse model of Alzheimer’s disease ameliorates amyloid pathologies and memory deficits. Brain 134(Pt 1):258–277
Yu WH, Cuervo AM, Kumar A, Peterhoff CM, Schmidt SD, Lee JH, Mohan PS, Mercken M, Farmery MR, Tjernberg LO, Jiang Y, Duff K, Uchiyama Y, Näslund J, Mathews PM, Cataldo AM, Nixon RA (2005) Macroautophagy—a novel beta-amyloid peptide-generating pathway activated in Alzheimer’s disease. J Cell Biol 171(1):87–98
Sun YX, Ji X, Mao X, Xie L, Jia J, Galvan V, Greenberg DA, Jin K (2013) Differential activation of mTOR complex 1 signaling in human brain with mild to severe Alzheimer’s disease. J Alzheimers Dis 38(2):437–444
Wen YD, Sheng R, Zhang LS, Han R, Zhang X, Zhang XD, Han F, Fukunaga K, Qin ZH (2008) Neuronal injury in rat model of permanent focal cerebral ischemia is associated with activation of autophagic and lysosomal pathways. Autophagy 4(6):762–769
Puyal J, Vaslin A, Mottier V, Clarke PG (2009) Postischemic treatment of neonatal cerebral ischemia should target autophagy. Ann Neurol 66(3):378–389
Balduini W, Carloni S, Buonocore G (2012) Autophagy in hypoxia-ischemia induced brain injury. J Matern Fetal Neonatal Med 25(Suppl 1):30–34
Koike M, Shibata M, Tadakoshi M, Gotoh K, Komatsu M, Waguri S, Kawahara N, Kuida K, Nagata S, Kominami E, Tanaka K, Uchiyama Y (2008) Inhibition of autophagy prevents hippocampal pyramidal neuron death after hypoxic-ischemic injury. Am J Pathol 172(2):454–469
Nitatori T, Sato N, Kominami E (1996) Participation of cathepsins B, H, and L in perikaryal condensation of CA1 pyramidal neurons undergoing apoptosis after brief ischemia. Adv Exp Med Biol 389:177–185
Xu M, Zhang HL (2011) Death and survival of neuronal and astrocytic cells in ischemic brain injury: a role of autophagy. Acta Pharmacol Sin 32(9):1089–1099
Carloni S, Buonocore G, Balduini W (2008) Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiol Dis 32(3):329–339
Liu C, Gao Y, Barrett J, Hu B (2010) Autophagy and protein aggregation after brain ischemia. J Neurochem 115(1):68–78
Zheng C, Han J, Xia W, Shi S, Liu J, Ying W (2012) NAD(+) administration decreases ischemic brain damage partially by blocking autophagy in a mouse model of brain ischemia. Neurosci Lett 512(2):67–71
Fiskum G (2000) Mitochondrial participation in ischemic and traumatic neural cell death. J Neurotrauma 17(10):843–855
Shi R, Weng J, Zhao L, Li XM, Gao TM, Kong J (2012) Excessive autophagy contributes to neuron death in cerebral ischemia. CNS Neurosci Ther 18(3):250–260
Puyal J, Ginet V, Grishchuk Y, Truttmann AC, Clarke PG (2012) Neuronal autophagy as a mediator of life and death: contrasting roles in chronic neurodegenerative and acute neural disorders. Neuroscientist 18(3):224–336
Borsello T, Croquelois K, Hornung JP, Clarke PG (2003) N-methyl-d-aspartate-triggered neuronal death in organotypic hippocampal cultures is endocytic, autophagic and mediated by the c-Jun N-terminal kinase pathway. Eur J Neurosci 18(3):473–485
Shacka JJ, Lu J, Xie ZL, Uchiyama Y, Roth KA, Zhang J (2007) Kainic acid induces early and transient autophagic stress in mouse hippocampus. Neurosci Lett 414(1):57–60
Wu YT, Tan HL, Shui G, Bauvy C, Huang Q, Wenk MR, Ong CN, Codogno P, Shen HM (2010) Dual role of 3-methyladenine in modulation of autophagy via different temporal patterns of inhibition on class I and III phosphoinositide 3-kinase. J Biol Chem 285(14):10850–108561
Fukui K, Kawakami H, Honjo T, Ogasawara R, Takatsu H, Shinkai T, Koike T, Urano S (2012) Vitamin E deficiency induces axonal degeneration in mouse hippocampal neurons. J Nutr Sci Vitaminol (Tokyo) 58(6):377–383
Acknowledgments
This work was supported by a grant from the National Natural Science Foundation of China (no. 81370183) and a grant from Natural Science Foundation of Tianjin (no. 13JCYBJC23700).
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Li, L., Zhang, Q., Tan, J. et al. Autophagy and hippocampal neuronal injury. Sleep Breath 18, 243–249 (2014). https://doi.org/10.1007/s11325-013-0930-4
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DOI: https://doi.org/10.1007/s11325-013-0930-4