Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis

Subhash Kulkarni, Maria Adelaide Micci, Jenna Leser, Changsik Shin, Shiue Cheng Tang, Ya Yuan Fu, Liansheng Liu, Qian Li, Monalee Saha, Cuiping Li, Grigori Enikolopov, Laren Becker, Nikolai Rakhilin, Michael Anderson, Xiling Shen, Xinzhong Dong, Manish J. Butte, Hongjun Song, E. Michelle Southard-Smith, Raj P. Kapur & 2 others Milena Bogunovic, Pankaj J. Pasricha

Research output: Contribution to journalArticle

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Abstract

According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease.

Original languageEnglish (US)
Pages (from-to)E3709-E3718
JournalProceedings of the National Academy of Sciences of the United States of America
Volume114
Issue number18
DOIs
StatePublished - May 2 2017

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Enteric Nervous System
Neurogenesis
Apoptosis
Ganglia
Health
Neurons
Gene Pool
Nestin
Phosphoric Monoester Hydrolases
Neuroglia
Small Intestine
Homeostasis
Mutation
Population

All Science Journal Classification (ASJC) codes

  • General

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Kulkarni, Subhash ; Micci, Maria Adelaide ; Leser, Jenna ; Shin, Changsik ; Tang, Shiue Cheng ; Fu, Ya Yuan ; Liu, Liansheng ; Li, Qian ; Saha, Monalee ; Li, Cuiping ; Enikolopov, Grigori ; Becker, Laren ; Rakhilin, Nikolai ; Anderson, Michael ; Shen, Xiling ; Dong, Xinzhong ; Butte, Manish J. ; Song, Hongjun ; Southard-Smith, E. Michelle ; Kapur, Raj P. ; Bogunovic, Milena ; Pasricha, Pankaj J. / Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis. In: Proceedings of the National Academy of Sciences of the United States of America. 2017 ; Vol. 114, No. 18. pp. E3709-E3718.
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abstract = "According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease.",
author = "Subhash Kulkarni and Micci, {Maria Adelaide} and Jenna Leser and Changsik Shin and Tang, {Shiue Cheng} and Fu, {Ya Yuan} and Liansheng Liu and Qian Li and Monalee Saha and Cuiping Li and Grigori Enikolopov and Laren Becker and Nikolai Rakhilin and Michael Anderson and Xiling Shen and Xinzhong Dong and Butte, {Manish J.} and Hongjun Song and Southard-Smith, {E. Michelle} and Kapur, {Raj P.} and Milena Bogunovic and Pasricha, {Pankaj J.}",
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Kulkarni, S, Micci, MA, Leser, J, Shin, C, Tang, SC, Fu, YY, Liu, L, Li, Q, Saha, M, Li, C, Enikolopov, G, Becker, L, Rakhilin, N, Anderson, M, Shen, X, Dong, X, Butte, MJ, Song, H, Southard-Smith, EM, Kapur, RP, Bogunovic, M & Pasricha, PJ 2017, 'Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis', Proceedings of the National Academy of Sciences of the United States of America, vol. 114, no. 18, pp. E3709-E3718. https://doi.org/10.1073/pnas.1619406114

Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis. / Kulkarni, Subhash; Micci, Maria Adelaide; Leser, Jenna; Shin, Changsik; Tang, Shiue Cheng; Fu, Ya Yuan; Liu, Liansheng; Li, Qian; Saha, Monalee; Li, Cuiping; Enikolopov, Grigori; Becker, Laren; Rakhilin, Nikolai; Anderson, Michael; Shen, Xiling; Dong, Xinzhong; Butte, Manish J.; Song, Hongjun; Southard-Smith, E. Michelle; Kapur, Raj P.; Bogunovic, Milena; Pasricha, Pankaj J.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 18, 02.05.2017, p. E3709-E3718.

Research output: Contribution to journalArticle

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T1 - Adult enteric nervous system in health is maintained by a dynamic balance between neuronal apoptosis and neurogenesis

AU - Kulkarni, Subhash

AU - Micci, Maria Adelaide

AU - Leser, Jenna

AU - Shin, Changsik

AU - Tang, Shiue Cheng

AU - Fu, Ya Yuan

AU - Liu, Liansheng

AU - Li, Qian

AU - Saha, Monalee

AU - Li, Cuiping

AU - Enikolopov, Grigori

AU - Becker, Laren

AU - Rakhilin, Nikolai

AU - Anderson, Michael

AU - Shen, Xiling

AU - Dong, Xinzhong

AU - Butte, Manish J.

AU - Song, Hongjun

AU - Southard-Smith, E. Michelle

AU - Kapur, Raj P.

AU - Bogunovic, Milena

AU - Pasricha, Pankaj J.

PY - 2017/5/2

Y1 - 2017/5/2

N2 - According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease.

AB - According to current dogma, there is little or no ongoing neurogenesis in the fully developed adult enteric nervous system. This lack of neurogenesis leaves unanswered the question of how enteric neuronal populations are maintained in adult guts, given previous reports of ongoing neuronal death. Here, we confirm that despite ongoing neuronal cell loss because of apoptosis in the myenteric ganglia of the adult small intestine, total myenteric neuronal numbers remain constant. This observed neuronal homeostasis is maintained by new neurons formed in vivo from dividing precursor cells that are located within myenteric ganglia and express both Nestin and p75NTR, but not the pan-glial marker Sox10. Mutation of the phosphatase and tensin homolog gene in this pool of adult precursors leads to an increase in enteric neuronal number, resulting in ganglioneuromatosis, modeling the corresponding disorder in humans. Taken together, our results show significant turnover and neurogenesis of adult enteric neurons and provide a paradigm for understanding the enteric nervous system in health and disease.

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U2 - 10.1073/pnas.1619406114

DO - 10.1073/pnas.1619406114

M3 - Article

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JF - Proceedings of the National Academy of Sciences of the United States of America

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