Skip to main content

Advertisement

SpringerLink
Log in

Postnatal development of BAG3 expression in mouse cerebral cortex and hippocampus

  • Original Article
  • Published:
Brain Structure and Function Aims and scope Submit manuscript

Abstract

The decreased efficiency of autophagic processing in the central nervous system during aging may be a contributing factor in neurodegenerative diseases. BAG3 (Bcl2 associated athanogene 3) is a major member of the BAG family of co-molecular chaperones that mediate selective macroautophagy. Therefore, we analyzed the expression and distribution of BAG3 in the brain at postnatal 0 day (P0), P15, 1-, 2-, 9-, 12-, and 18 month-old C57BL/6 mice, thus covering almost all ages. Except for a significant steep drop in mRNA and protein levels in the cortex and hippocampus soon after birth, there were minimal differences in the expression and distribution of BAG3 among P15, M1, M2, M9, and M12 mice; however, at 18 months, BAG3 expression was significantly higher. Immunohistochemical analyses showed that BAG3 is mainly located in the neuronal cytoplasm and processes in C57BL/6 the cerebral cortex and hippocampus from P0 to M18 postnatal development. These findings indicate that BAG3 might be stable in young and middle-aged mice, but unstable in aged mice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

Data availability

All original data in this study are available from the corresponding author on request.

References

  • Aimone JB, Li Y, Lee SW, Clemenson GD, Deng W, Gage FH (2014) Regulation and function of adult neurogenesis: from genes to cognition. Physiol Rev 94(4):991–1026

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boland B, Kumar A, Lee S, Platt FM, Wegiel J, Yu WH, Nixon RA (2008) Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci 28(27):6926–6937

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bonfanti L, Nacher J (2012) New scenarios for neuronal structural plasticity in non-neurogenic brain parenchyma: the case of cortical layer II immature neurons. Prog Neurobiol 98(1):1–15

    Article  PubMed  Google Scholar 

  • Burek MJ, Oppenheim RW (1996) Programmed cell death in the developing nervous system. Brain Pathol 6(4):427–446

    Article  CAS  PubMed  Google Scholar 

  • Buss RR, Sun W, Oppenheim RW (2006) Adaptive roles of programmed cell death during nervous system development. Annu Rev Neurosci 29:1–35

    Article  CAS  PubMed  Google Scholar 

  • Choi JS, Lee JH, Kim HY, Chun MH, Chung JW, Lee MY (2006) Developmental expression of Bis protein in the cerebral cortex and hippocampus of rats. Brain Res 1092(1):69–78

    Article  CAS  PubMed  Google Scholar 

  • Dan W, Gao N, Li L, Zhu JX, Diao L, Huang J, Han QJ, Wang S, Xue H, Wang Q, Wu QF, Zhang X, Bao L (2017) Alpha-tubulin acetylation restricts axon overbranching by dampening microtubule plus-end dynamics in neurons. Cereb Cortex 28(9):3332–3346

    Article  Google Scholar 

  • David DC (2012) Aging and the aggregating proteome. Front Genet 3:247

    Article  PubMed  PubMed Central  Google Scholar 

  • El Waly B, Macchi M, Cayre M, Durbec P (2014) Oligodendrogenesis in the normal and pathological central nervous system. Front Neurosci 8:145

    PubMed  PubMed Central  Google Scholar 

  • Farhy-Tselnicker I, Allen NJ (2018) Astrocytes, neurons, synapses: a tripartite view on cortical circuit development. Neural Dev 13(1):7

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Ferrer I, Soriano E, del Rio JA, Alcantara S, Auladell C (1992) Cell death and removal in the cerebral cortex during development. Prog Neurobiol 39(1):1–43

    Article  CAS  PubMed  Google Scholar 

  • Fjell AM, McEvoy L, Holland D, Dale AM, Walhovd KB, Initi AsDN (2014) What is normal in normal aging? Effects of aging, amyloid and Alzheimer’s disease on the cerebral cortex and the hippocampus. Prog Neurobiol 117:20–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flurkey K, Currer JM, DE Harrison (2007) Mouse models in aging research. The mouse in biomedical research, 2nd edn. American College Laboratory Animal Medicine. Elsevier, Burlington, pp 637–672

    Chapter  Google Scholar 

  • Fraklin KBJ, Paxinos G (2007) The Mouse brain in stereotaxic coordinates, 3rd edn. Academic Press, Cambridge

    Google Scholar 

  • Fu H, Possenti A, Freer R, Nakano Y, Hernandez Villegas NC, Tang M, Cauhy PVM, Lassus BA, Chen S, Fowler SL, Figueroa HY, Huey ED, Johnson GVW, Vendruscolo M, Duff KE (2019) A tau homeostasis signature is linked with the cellular and regional vulnerability of excitatory neurons to tau pathology. Nat Neurosci 22(1):47–56

    Article  CAS  PubMed  Google Scholar 

  • Gamerdinger M, Hajieva P, Kaya AM, Wolfrum U, Hartl FU, Behl C (2009) Protein quality control during aging involves recruitment of the macroautophagy pathway by BAG3. EMBO J 28(7):889–901

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gamerdinger M, Kaya AM, Wolfrum U, Clement AM, Behl C (2011) BAG3 mediates chaperone-based aggresome-targeting and selective autophagy of misfolded proteins. EMBO Rep 12(2):149–156

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gentilella A, Khalili K (2010) BAG3 expression is sustained by FGF2 in neural progenitor cells and impacts cell proliferation. Cell Cycle 9(20):4245–4247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gestwicki JE, Garza D (2012) Protein quality control in neurodegenerative disease. Prog Mol Biol Transl Sci 107:327–353

    Article  CAS  PubMed  Google Scholar 

  • Ghasemi Tahrir F, Gupta M, Myers V, Gordon J, Cheung JY, Feldman AM, Khalili K (2019) Role of Bcl2-associated athanogene 3 in turnover of gap junction protein, connexin 43 neonatal cardiomyocytes. Sci Rep 9(1):7658

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gomez-Climent MA, Castillo-Gomez E, Varea E, Guirado R, Blasco-Ibanez JM, Crespo C, Martinez-Guijarro FJ, Nacher J (2008) A population of prenatally generated cells in the rat paleocortex maintains an immature neuronal phenotype into adulthood. Cereb Cortex 18(10):2229–2240

    Article  PubMed  Google Scholar 

  • 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

    Article  CAS  PubMed  Google Scholar 

  • Jenkins BV, Saunders HAJ, Record HL, Johnson-Schlitz DM, Wildonger J (2017) Effects of mutating alpha-tubulin lysine 40 on sensory dendrite development. J Cell Sci 130(24):4120–4131

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ji C, Tang M, Zeidler C, Hohfeld J, Johnson GV (2019) BAG3 and SYNPO (synaptopodin) facilitate phospho-MAPT/Tau degradation via autophagy in neuronal processes. Autophagy 15(7):1199–1213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kandel ER, Schwartz JH, Jessell TM, Siegelbaum SA, Hudspeth AJ (2013) Principles of neural science. McGraw-Hill Medical, New York

    Google Scholar 

  • Khodosevich K, Alfonso J, Monyer H (2013) Dynamic changes in the transcriptional profile of subventricular zone-derived postnatally born neuroblasts. Mech Dev 130(6–8):424–432

    Article  CAS  PubMed  Google Scholar 

  • Lee JC, Koh SA, Lee KH, Kim JR (2019) BAG3 contributes to HGF-mediated cell proliferation, migration, and invasion via the Egr1 pathway in gastric cancer. Tumori 105(1):63–75

    Article  CAS  PubMed  Google Scholar 

  • Lei Z, Brizzee C, Johnson GV (2015) BAG3 facilitates the clearance of endogenous tau in primary neurons. Neurobiol Aging 36(1):241–248

    Article  CAS  PubMed  Google Scholar 

  • Li L, Yang XJ (2015) Tubulin acetylation: responsible enzymes, biological functions and human diseases. Cell Mol Life Sci 72(22):4237–4255

    Article  CAS  PubMed  Google Scholar 

  • Li N, Chen M, Cao Y, Li H, Zhao J, Zhai Z, Ren F, Li K (2018) Bcl-2-associated athanogene 3(BAG3) is associated with tumor cell proliferation, migration, invasion and chemoresistance in colorectal cancer. BMC Cancer 18(1):793

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu BQ, Du ZX, Zong ZH, Li C, Li N, Zhang Q, Kong DH, Wang HQ (2013) BAG3-dependent noncanonical autophagy induced by proteasome inhibition in HepG2 cells. Autophagy 9(6):905–916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McNaughton BL, Battaglia FP, Jensen O, Moser EI, Moser MB (2006) Path integration and the neural basis of the ‘cognitive map.’ Nat Rev Neurosci 7(8):663–678

    Article  CAS  PubMed  Google Scholar 

  • Minoia M, Boncoraglio A, Vinet J, Morelli FF, Brunsting JF, Poletti A, Krom S, Reits E, Kampinga HH, Carra S (2014) BAG3 induces the sequestration of proteasomal clients into cytoplasmic puncta: implications for a proteasome-to-autophagy switch. Autophagy 10(9):1603–1621

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mouret A, Gheusi G, Gabellec MM, de Chaumont F, Olivo-Marin JC, Lledo PM (2008) Learning and survival of newly generated neurons: when time matters. J Neurosci 28(45):11511–11516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Oo TF, Burke RE (1997) The time course of developmental cell death in phenotypically defined dopaminergic neurons of the substantia nigra. Brain Res Dev Brain Res 98(2):191–196

    Article  CAS  PubMed  Google Scholar 

  • Rowland DC, Roudi Y, Moser MB, Moser EI (2016) Ten years of grid cells. Annu Rev Neurosci 39:19–40

    Article  CAS  PubMed  Google Scholar 

  • Santoro A, Nicolin V, Florenzano F, Rosati A, Capunzo M, Nori SL (2017) BAG3 is involved in neuronal differentiation and migration. Cell Tissue Res 368(2):249–258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Shi H, Xu H, Li Z, Zhen Y, Wang B, Huo S, Xiao R, Xu Z (2016) BAG3 regulates cell proliferation, migration, and invasion in human colorectal cancer. Tumour Biol 37(4):5591–5597

    Article  CAS  PubMed  Google Scholar 

  • Soukup SF, Kuenen S, Vanhauwaert R, Manetsberger J, Hernandez-Diaz S, Swerts J, Schoovaerts N, Vilain S, Gounko NV, Vints K, Geens A, De Strooper B, Verstreken P (2016) A LRRK2-dependent endophilina phosphoswitch is critical for macroautophagy at presynaptic terminals. Neuron 92(4):829–844

    Article  CAS  PubMed  Google Scholar 

  • Southwell DG, Paredes MF, Galvao RP, Jones DL, Froemke RC, Sebe JY, Alfaro-Cervello C, Tang Y, Garcia-Verdugo JM, Rubenst Jein JL, Baraban SC, Alvarez-Buylla A (2012) Intrinsically determined cell death of developing cortical interneurons. Nature 491(7422):109–113

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tang M, Ji C, Pallo S, Rahman I, Johnson GVW (2018) Nrf2 mediates the expression of BAG3 and autophagy cargo adaptor proteins and tau clearance in an age-dependent manner. Neurobiol Aging 63:128–139

    Article  CAS  PubMed  Google Scholar 

  • Ulbricht A, Eppler FJ, Tapia VE, van der Ven PF, Hampe N, Hersch N, Vakeel P, Stadel D, Haas A, Saftig P, Behrends C, Furst DO, Volkmer R, Hoffmann B, Kolanus W, Hohfeld J (2013) Cellular mechanotransduction relies on tension-induced and chaperone-assisted autophagy. Curr Biol 23(5):430–435

    Article  CAS  PubMed  Google Scholar 

  • van Praag H, Kempermann G, Gage FH (1999) Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus. Nat Neurosci 2(3):266–270

    Article  PubMed  Google Scholar 

  • Vanhauwaert R, Kuenen S, Masius R, Bademosi A, Manetsberger J, Schoovaerts N, Bounti L, Gontcharenko S, Swerts J, Vilain S, Picillo M, Barone P, Munshi ST, de Vrij FM, Kushner SA, Gounko NV, Mandemakers W, Bonifati V, Meunier FA, Soukup SF, Verstreken P (2017) The SAC1 domain in synaptojanin is required for autophagosome maturation at presynaptic terminals. EMBO J 36(10):1392–1411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vidal RL, Matus S, Bargsted L, Hetz C (2014) Targeting autophagy in neurodegenerative diseases. Trends Pharmacol Sci 35(11):583–591

    Article  CAS  PubMed  Google Scholar 

  • Yuan Y, Jiang JY, Wang JM, Sun J, Li C, Liu BQ, Yan J, Meng XN, Wang HQ (2019) BAG3-positive pancreatic stellate cells promote migration and invasion of pancreatic ductal adenocarcinoma. J Cell Mol Med 23(8):5006–5016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou J, Chow HM, Liu Y, Wu D, Shi M, Li J, Wen L, Gao Y, Chen G, Zhuang K, Lin H, Zhang G, Xie W, Li H, Leng L, Wang M, Zheng N, Sun H, Zhao Y, Zhang Y, Xue M, Huang TY, Bu G, Xu H, Yuan Z, Herrup K, Zhang J (2020) Cyclin-dependent kinase 5-dependent BAG3 degradation modulates synaptic protein turnover. Biol Psychiatry 87(8):756–769

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work is supported by grants from the Natural Science Foundation of China (81471112, 81000468, 81771174, and 81601113). The authors would like to thank Editage (www.editage.com) for English editing.

Author information

Author notes

  1. Xinlu Li and Geng Lin have contributed equally to this work.

Authors and Affiliations

  1. Department of Histology and Embryology, China Medical University, Shenyang, 110122, China

    Xinlu Li, Geng Lin, Tongtong Liu & Wei Zheng

  2. Department of Neurology, The People’s Hospital of Liaoning Province, Shenyang, 110016, China

    Tongtong Liu

  3. Department of Infectious Diseases, Shengjing Hospital, Affiliated Hospital of China Medical University, Shenyang, 110022, China

    Ning Zhao

  4. Department of Histology and Embryology, School of Medicine, Shenzhen University, Shenzhen, 518052, China

    He Xu

  5. Department of Biochemistry and Molecular Biology, China Medical University, Shenyang, 110122, China

    Huaqin Wang

Authors
  1. Xinlu Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Geng Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tongtong Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ning Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. He Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Huaqin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Wei Zheng
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

WZ and H-QW conceived and designed the study. X-LL, GL, T-TL, and NZ performed the experiments and data analyses. X-LL and HX drafted the manuscript. WZ finalized the article. All authors read and approved the manuscript.

Corresponding author

Correspondence to Wei Zheng.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest related to the presented work.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Li, X., Lin, G., Liu, T. et al. Postnatal development of BAG3 expression in mouse cerebral cortex and hippocampus. Brain Struct Funct 226, 2629–2650 (2021). https://doi.org/10.1007/s00429-021-02356-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00429-021-02356-y

Keywords

Search

Navigation