Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system

Marton Lorant Toth, Ilija Melentijevic, Leena Shah, Aatish Bhatia, Kevin Lu, Amish Talwar, Haaris Naji, Carolina Ibanez-Ventoso, Piya Ghose, Angela Jevince, Jian Xue, Laura A. Herndon, Gyan Bhanot, Chris Rongo, David H. Hall, Monica Driscoll

Research output: Contribution to journalArticle

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Abstract

Caenorhabditis elegans is a powerful model for analysis of the conserved mechanisms that modulate healthy aging. In the aging nematode nervous system, neuronal death and/or detectable loss of processes are not readily apparent, but because dendrite restructuring and loss of synaptic integrity are hypothesized to contribute to human brain decline and dysfunction, we combined fluorescence microscopy and electron microscopy (EM) to screen at high resolution for nervous system changes. We report two major components of morphological change in the aging C. elegans nervous system: (1) accumulation of novel outgrowths from specific neurons, and (2) physical decline in synaptic integrity. Novel outgrowth phenotypes, including branching from the main dendrite or new growth from somata, appear at a high frequency in some aging neurons, but not all. Mitochondria are often associated with age-associated branch sites. Lowered insulin signaling confers some maintenance of ALM and PLM neuron structural integrity into old age, and both DAF-16/FOXO and heat shock factor transcription factor HSF-1 exert neuroprotective functions. hsf-1 can act cell autonomously in this capacity. EM evaluation in synapse-rich regions reveals a striking decline in synaptic vesicle numbers and a diminution of presynaptic density size. Interestingly, old animals that maintain locomotory prowess exhibit less synaptic decline than same-age decrepit animals, suggesting that synaptic integrity correlates with locomotory healthspan. Our data reveal similarities between the aging C. elegans nervous system and mammalian brain, suggesting conserved neuronal responses to age. Dissection of neuronal aging mechanisms in C. elegans may thus influence the development of brain healthspan-extending therapies.

Original languageEnglish (US)
Pages (from-to)8778-8790
Number of pages13
JournalJournal of Neuroscience
Volume32
Issue number26
DOIs
StatePublished - Jun 27 2012

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Caenorhabditis elegans
Neurites
Synapses
Nervous System
Dendrites
Neurons
Electron Microscopy
Brain
Synaptic Vesicles
Carisoprodol
Fluorescence Microscopy
Dissection
Shock
Mitochondria
Transcription Factors
Hot Temperature
Maintenance
Insulin
Phenotype
Growth

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Toth, M. L., Melentijevic, I., Shah, L., Bhatia, A., Lu, K., Talwar, A., ... Driscoll, M. (2012). Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system. Journal of Neuroscience, 32(26), 8778-8790. https://doi.org/10.1523/JNEUROSCI.1494-11.2012

Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system. / Toth, Marton Lorant; Melentijevic, Ilija; Shah, Leena; Bhatia, Aatish; Lu, Kevin; Talwar, Amish; Naji, Haaris; Ibanez-Ventoso, Carolina; Ghose, Piya; Jevince, Angela; Xue, Jian; Herndon, Laura A.; Bhanot, Gyan; Rongo, Chris; Hall, David H.; Driscoll, Monica.

In: Journal of Neuroscience, Vol. 32, No. 26, 27.06.2012, p. 8778-8790.

Research output: Contribution to journalArticle

Toth, ML, Melentijevic, I, Shah, L, Bhatia, A, Lu, K, Talwar, A, Naji, H, Ibanez-Ventoso, C, Ghose, P, Jevince, A, Xue, J, Herndon, LA, Bhanot, G, Rongo, C, Hall, DH & Driscoll, M 2012, 'Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system', Journal of Neuroscience, vol. 32, no. 26, pp. 8778-8790. https://doi.org/10.1523/JNEUROSCI.1494-11.2012
Toth, Marton Lorant ; Melentijevic, Ilija ; Shah, Leena ; Bhatia, Aatish ; Lu, Kevin ; Talwar, Amish ; Naji, Haaris ; Ibanez-Ventoso, Carolina ; Ghose, Piya ; Jevince, Angela ; Xue, Jian ; Herndon, Laura A. ; Bhanot, Gyan ; Rongo, Chris ; Hall, David H. ; Driscoll, Monica. / Neurite sprouting and synapse deterioration in the aging Caenorhabditis elegans nervous system. In: Journal of Neuroscience. 2012 ; Vol. 32, No. 26. pp. 8778-8790.
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