Enhanced glutamatergic and decreased GABAergic synaptic appositions to GnRH neurons on proestrus in the rat: modulatory effect of aging.

<h4>Background</h4>Previous work by our lab and others has implicated glutamate as a major excitatory signal to gonadotropin hormone releasing hormone (GnRH) neurons, with gamma amino butyric acid (GABA) serving as a potential major inhibitory signal. However, it is unknown whether GABAe...

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Main Authors: Mohammad Khan, Liesl De Sevilla, Virendra B Mahesh, Darrell W Brann
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2010-04-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0010172&type=printable
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author Mohammad Khan
Liesl De Sevilla
Virendra B Mahesh
Darrell W Brann
author_facet Mohammad Khan
Liesl De Sevilla
Virendra B Mahesh
Darrell W Brann
author_sort Mohammad Khan
collection DOAJ
description <h4>Background</h4>Previous work by our lab and others has implicated glutamate as a major excitatory signal to gonadotropin hormone releasing hormone (GnRH) neurons, with gamma amino butyric acid (GABA) serving as a potential major inhibitory signal. However, it is unknown whether GABAergic and/or glutamatergic synaptic appositions to GnRH neurons changes on the day of the proestrous LH surge or is affected by aging.<h4>Methodology/principal findings</h4>To examine this question, synaptic terminal appositions on GnRH neurons for VGAT (vesicular GABA transporter) and VGLUT2 (vesicular glutamate transporter-2), markers of GABAergic and glutamatergic synaptic terminals, respectively, was examined by immunohistochemistry and confocal microscopic analysis in young and middle-aged diestrous and proestrous rats. The results show that in young proestrous rats at the time of LH surge, we observed reciprocal changes in the VGAT and VGLUT2 positive terminals apposing GnRH neurons, where VGAT terminal appositions were decreased and VGLUT2 terminal appositions were significantly increased, as compared to young diestrus control animals. Interestingly, in middle-aged cycling animals this divergent modulation of VGAT and VGLUT2 terminal apposition was greatly impaired, as no significant differences were observed between VGAT and VGLUT2 terminals apposing GnRH neurons at proestrous. However, the density of VGAT and VGLUT2 terminals apposing GnRH neurons were both significantly increased in the middle-aged animals.<h4>Conclusions/significance</h4>In conclusion, there is an increase in glutamatergic and decrease in GABAergic synaptic terminal appositions on GnRH neurons on proestrus in young animals, which may serve to facilitate activation of GnRH neurons. In contrast, middle-aged diestrous and proestrous animals show a significant increase in both VGAT and VGLUT synaptic terminal appositions on GnRH neurons as compared to young animals, and the cycle-related change in these appositions between diestrus and proestrus that is observed in young animals is lost.
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spelling doaj-art-39763b0861bd4e76a0870bb5ec4585832025-08-20T03:07:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-04-0154e1017210.1371/journal.pone.0010172Enhanced glutamatergic and decreased GABAergic synaptic appositions to GnRH neurons on proestrus in the rat: modulatory effect of aging.Mohammad KhanLiesl De SevillaVirendra B MaheshDarrell W Brann<h4>Background</h4>Previous work by our lab and others has implicated glutamate as a major excitatory signal to gonadotropin hormone releasing hormone (GnRH) neurons, with gamma amino butyric acid (GABA) serving as a potential major inhibitory signal. However, it is unknown whether GABAergic and/or glutamatergic synaptic appositions to GnRH neurons changes on the day of the proestrous LH surge or is affected by aging.<h4>Methodology/principal findings</h4>To examine this question, synaptic terminal appositions on GnRH neurons for VGAT (vesicular GABA transporter) and VGLUT2 (vesicular glutamate transporter-2), markers of GABAergic and glutamatergic synaptic terminals, respectively, was examined by immunohistochemistry and confocal microscopic analysis in young and middle-aged diestrous and proestrous rats. The results show that in young proestrous rats at the time of LH surge, we observed reciprocal changes in the VGAT and VGLUT2 positive terminals apposing GnRH neurons, where VGAT terminal appositions were decreased and VGLUT2 terminal appositions were significantly increased, as compared to young diestrus control animals. Interestingly, in middle-aged cycling animals this divergent modulation of VGAT and VGLUT2 terminal apposition was greatly impaired, as no significant differences were observed between VGAT and VGLUT2 terminals apposing GnRH neurons at proestrous. However, the density of VGAT and VGLUT2 terminals apposing GnRH neurons were both significantly increased in the middle-aged animals.<h4>Conclusions/significance</h4>In conclusion, there is an increase in glutamatergic and decrease in GABAergic synaptic terminal appositions on GnRH neurons on proestrus in young animals, which may serve to facilitate activation of GnRH neurons. In contrast, middle-aged diestrous and proestrous animals show a significant increase in both VGAT and VGLUT synaptic terminal appositions on GnRH neurons as compared to young animals, and the cycle-related change in these appositions between diestrus and proestrus that is observed in young animals is lost.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0010172&type=printable
spellingShingle Mohammad Khan
Liesl De Sevilla
Virendra B Mahesh
Darrell W Brann
Enhanced glutamatergic and decreased GABAergic synaptic appositions to GnRH neurons on proestrus in the rat: modulatory effect of aging.
PLoS ONE
title Enhanced glutamatergic and decreased GABAergic synaptic appositions to GnRH neurons on proestrus in the rat: modulatory effect of aging.
title_full Enhanced glutamatergic and decreased GABAergic synaptic appositions to GnRH neurons on proestrus in the rat: modulatory effect of aging.
title_fullStr Enhanced glutamatergic and decreased GABAergic synaptic appositions to GnRH neurons on proestrus in the rat: modulatory effect of aging.
title_full_unstemmed Enhanced glutamatergic and decreased GABAergic synaptic appositions to GnRH neurons on proestrus in the rat: modulatory effect of aging.
title_short Enhanced glutamatergic and decreased GABAergic synaptic appositions to GnRH neurons on proestrus in the rat: modulatory effect of aging.
title_sort enhanced glutamatergic and decreased gabaergic synaptic appositions to gnrh neurons on proestrus in the rat modulatory effect of aging
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0010172&type=printable
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