Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission Within the Cerebellar Cortex

Valerie L. Hedges; Gang Chen; Lei Yu; Amanda A. Krentzel; Joseph R. Starrett; Jing Ning Zhu; Piratheepan Suntharalingam; Luke Remage-Healey; Jian Jun Wang; Timothy J. Ebner; Paul G. Mermelstein

doi:10.1210/en.2018-00039

Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission Within the Cerebellar Cortex

Valerie L. Hedges, Gang Chen, Lei Yu, Amanda A. Krentzel, Joseph R. Starrett, Jing Ning Zhu, Piratheepan Suntharalingam, Luke Remage-Healey, Jian Jun Wang, Timothy J. Ebner, Paul G. Mermelstein

Neuroscience

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

Abstract

Estrogens affect cerebellar activity and cerebellum-based behaviors. Within the adult rodent cerebellum, the best-characterized action of estradiol is to enhance glutamatergic signaling. However, the mechanisms by which estradiol promotes glutamatergic neurotransmission remain unknown. Within the mouse cerebellum, we found that estrogen receptor activation of metabotropic glutamate receptor type 1a strongly enhances neurotransmission at the parallel fiber-Purkinje cell synapse. The blockade of local estrogen synthesis within the cerebellum results in a diminution of glutamatergic neurotransmission. Correspondingly, decreased estrogen availability via gonadectomy or blockade of aromatase activity negatively affects locomotor performance. These data indicate that locally derived, and not just gonad-derived, estrogens affect cerebellar physiology and function. In addition, estrogens were found to facilitate parallel fiber-Purkinje cell synaptic transmission in both sexes. As such, the actions of estradiol to support cerebellar neurotransmission and cerebellum-based behaviors might be fundamental to understanding the normal processing of activity within the cerebellar cortex.

Original language	English (US)
Pages (from-to)	1328-1338
Number of pages	11
Journal	Endocrinology
Volume	159
Issue number	3
DOIs	https://doi.org/10.1210/en.2018-00039
State	Published - Mar 1 2018

Bibliographical note

Funding Information:
Financial Support: This work was supported by the National Institute of Neurologic Disorders and Stroke (Grant NS077661 to P.G.M. and T.J.E.; Grants NS062158 and NS18338 to T.J.E.; and Grants NS066179 and NS082179 to L.R.-H.); the National Institute on Drug Abuse (Grants DA035008 and DA041808 to P.G.M.); the National Natural Science Foundation of China (Grants 31330033, 91332124, and 31461163001 to J.-J.W.; and Grants 81671107 and 31471112 to J.-N.Z.); the Specialized Research Fund for the Doctoral Program of Higher Education and Research Grants Council Earmarked Research Grants (Grant 20130091140003 to J.-J.W.); and the Jiangsu Natural Science Foundation (Grant BK2011014 to J.-J.W.).

Publisher Copyright:
Copyright © 2018 Endocrine Society.

Access

10.1210/en.2018-00039

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5839732

OpenUrl availability

Full text

Cite this

@article{0f0a1c2bbe52469f9d921baead3ba506,

title = "Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission Within the Cerebellar Cortex",

abstract = "Estrogens affect cerebellar activity and cerebellum-based behaviors. Within the adult rodent cerebellum, the best-characterized action of estradiol is to enhance glutamatergic signaling. However, the mechanisms by which estradiol promotes glutamatergic neurotransmission remain unknown. Within the mouse cerebellum, we found that estrogen receptor activation of metabotropic glutamate receptor type 1a strongly enhances neurotransmission at the parallel fiber-Purkinje cell synapse. The blockade of local estrogen synthesis within the cerebellum results in a diminution of glutamatergic neurotransmission. Correspondingly, decreased estrogen availability via gonadectomy or blockade of aromatase activity negatively affects locomotor performance. These data indicate that locally derived, and not just gonad-derived, estrogens affect cerebellar physiology and function. In addition, estrogens were found to facilitate parallel fiber-Purkinje cell synaptic transmission in both sexes. As such, the actions of estradiol to support cerebellar neurotransmission and cerebellum-based behaviors might be fundamental to understanding the normal processing of activity within the cerebellar cortex.",

author = "Hedges, {Valerie L.} and Gang Chen and Lei Yu and Krentzel, {Amanda A.} and Starrett, {Joseph R.} and Zhu, {Jing Ning} and Piratheepan Suntharalingam and Luke Remage-Healey and Wang, {Jian Jun} and Ebner, {Timothy J.} and Mermelstein, {Paul G.}",

note = "Funding Information: Financial Support: This work was supported by the National Institute of Neurologic Disorders and Stroke (Grant NS077661 to P.G.M. and T.J.E.; Grants NS062158 and NS18338 to T.J.E.; and Grants NS066179 and NS082179 to L.R.-H.); the National Institute on Drug Abuse (Grants DA035008 and DA041808 to P.G.M.); the National Natural Science Foundation of China (Grants 31330033, 91332124, and 31461163001 to J.-J.W.; and Grants 81671107 and 31471112 to J.-N.Z.); the Specialized Research Fund for the Doctoral Program of Higher Education and Research Grants Council Earmarked Research Grants (Grant 20130091140003 to J.-J.W.); and the Jiangsu Natural Science Foundation (Grant BK2011014 to J.-J.W.). Publisher Copyright: Copyright {\textcopyright} 2018 Endocrine Society.",

year = "2018",

month = mar,

day = "1",

doi = "10.1210/en.2018-00039",

language = "English (US)",

volume = "159",

pages = "1328--1338",

journal = "Endocrinology",

issn = "0013-7227",

publisher = "The Endocrine Society",

number = "3",

}

TY - JOUR

T1 - Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission Within the Cerebellar Cortex

AU - Hedges, Valerie L.

AU - Chen, Gang

AU - Yu, Lei

AU - Krentzel, Amanda A.

AU - Starrett, Joseph R.

AU - Zhu, Jing Ning

AU - Suntharalingam, Piratheepan

AU - Remage-Healey, Luke

AU - Wang, Jian Jun

AU - Ebner, Timothy J.

AU - Mermelstein, Paul G.

N1 - Funding Information: Financial Support: This work was supported by the National Institute of Neurologic Disorders and Stroke (Grant NS077661 to P.G.M. and T.J.E.; Grants NS062158 and NS18338 to T.J.E.; and Grants NS066179 and NS082179 to L.R.-H.); the National Institute on Drug Abuse (Grants DA035008 and DA041808 to P.G.M.); the National Natural Science Foundation of China (Grants 31330033, 91332124, and 31461163001 to J.-J.W.; and Grants 81671107 and 31471112 to J.-N.Z.); the Specialized Research Fund for the Doctoral Program of Higher Education and Research Grants Council Earmarked Research Grants (Grant 20130091140003 to J.-J.W.); and the Jiangsu Natural Science Foundation (Grant BK2011014 to J.-J.W.). Publisher Copyright: Copyright © 2018 Endocrine Society.

PY - 2018/3/1

Y1 - 2018/3/1

N2 - Estrogens affect cerebellar activity and cerebellum-based behaviors. Within the adult rodent cerebellum, the best-characterized action of estradiol is to enhance glutamatergic signaling. However, the mechanisms by which estradiol promotes glutamatergic neurotransmission remain unknown. Within the mouse cerebellum, we found that estrogen receptor activation of metabotropic glutamate receptor type 1a strongly enhances neurotransmission at the parallel fiber-Purkinje cell synapse. The blockade of local estrogen synthesis within the cerebellum results in a diminution of glutamatergic neurotransmission. Correspondingly, decreased estrogen availability via gonadectomy or blockade of aromatase activity negatively affects locomotor performance. These data indicate that locally derived, and not just gonad-derived, estrogens affect cerebellar physiology and function. In addition, estrogens were found to facilitate parallel fiber-Purkinje cell synaptic transmission in both sexes. As such, the actions of estradiol to support cerebellar neurotransmission and cerebellum-based behaviors might be fundamental to understanding the normal processing of activity within the cerebellar cortex.

AB - Estrogens affect cerebellar activity and cerebellum-based behaviors. Within the adult rodent cerebellum, the best-characterized action of estradiol is to enhance glutamatergic signaling. However, the mechanisms by which estradiol promotes glutamatergic neurotransmission remain unknown. Within the mouse cerebellum, we found that estrogen receptor activation of metabotropic glutamate receptor type 1a strongly enhances neurotransmission at the parallel fiber-Purkinje cell synapse. The blockade of local estrogen synthesis within the cerebellum results in a diminution of glutamatergic neurotransmission. Correspondingly, decreased estrogen availability via gonadectomy or blockade of aromatase activity negatively affects locomotor performance. These data indicate that locally derived, and not just gonad-derived, estrogens affect cerebellar physiology and function. In addition, estrogens were found to facilitate parallel fiber-Purkinje cell synaptic transmission in both sexes. As such, the actions of estradiol to support cerebellar neurotransmission and cerebellum-based behaviors might be fundamental to understanding the normal processing of activity within the cerebellar cortex.

UR - http://www.scopus.com/inward/record.url?scp=85042649336&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042649336&partnerID=8YFLogxK

U2 - 10.1210/en.2018-00039

DO - 10.1210/en.2018-00039

M3 - Article

C2 - 29381778

AN - SCOPUS:85042649336

SN - 0013-7227

VL - 159

SP - 1328

EP - 1338

JO - Endocrinology

JF - Endocrinology

IS - 3

ER -

Local Estrogen Synthesis Regulates Parallel Fiber-Purkinje Cell Neurotransmission Within the Cerebellar Cortex

Abstract

Bibliographical note

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this