Cotinine Enhances Fear Extinction and Astrocyte Survival by Mechanisms Involving the Nicotinic Acetylcholine Receptors Signaling
Fear memory extinction (FE) is an important therapeutic goal for Posttraumatic stress disorder (PTSD). Cotinine facilitates FE in rodents, in part due to its inhibitory effect on the amygdala by the glutamatergic projections from the medial prefrontal cortex (mPFC). The cellular and behavioral effec...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-04-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00303/full |
| _version_ | 1819113235987562496 |
|---|---|
| author | Patricia Oliveros-Matus Nelson Perez-Urrutia Nathalie Alvarez-Ricartes Florencia Echeverria George E. Barreto George E. Barreto James Elliott James Elliott Alexandre Iarkov Valentina Echeverria Valentina Echeverria |
| author_facet | Patricia Oliveros-Matus Nelson Perez-Urrutia Nathalie Alvarez-Ricartes Florencia Echeverria George E. Barreto George E. Barreto James Elliott James Elliott Alexandre Iarkov Valentina Echeverria Valentina Echeverria |
| author_sort | Patricia Oliveros-Matus |
| collection | DOAJ |
| description | Fear memory extinction (FE) is an important therapeutic goal for Posttraumatic stress disorder (PTSD). Cotinine facilitates FE in rodents, in part due to its inhibitory effect on the amygdala by the glutamatergic projections from the medial prefrontal cortex (mPFC). The cellular and behavioral effects of infusing cotinine into the mPFC on FE, astroglia survival, and the expression of bone morphogenetic proteins (BMP) 2 and 8, were assessed in C57BL/6 conditioned male mice. The role of the α4β2- and α7 nicotinic acetylcholine receptors (nAChRs) on cotinine’s actions were also investigated. Cotinine infused into the mPFC enhanced contextual FE and decreased BMP8 expression by a mechanism dependent on the α7nAChRs. In addition, cotinine increased BMP2 expression and prevented the loss of GFAP + astrocytes in a form independent on the α7nAChRs but dependent on the α4β2 nAChRs. This evidence suggests that cotinine exerts its effect on FE by modulating nAChRs signaling in the brain. |
| first_indexed | 2024-12-22T04:26:11Z |
| format | Article |
| id | doaj.art-8ca9c7e62cf54cc3b99ec46435d53646 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-22T04:26:11Z |
| publishDate | 2020-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-8ca9c7e62cf54cc3b99ec46435d536462022-12-21T18:39:10ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-04-011110.3389/fphar.2020.00303472516Cotinine Enhances Fear Extinction and Astrocyte Survival by Mechanisms Involving the Nicotinic Acetylcholine Receptors SignalingPatricia Oliveros-Matus0Nelson Perez-Urrutia1Nathalie Alvarez-Ricartes2Florencia Echeverria3George E. Barreto4George E. Barreto5James Elliott6James Elliott7Alexandre Iarkov8Valentina Echeverria9Valentina Echeverria10Laboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, ChileLaboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, ChileLaboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, ChileLaboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, ChileDepartment of Biological Sciences, University of Limerick, Limerick, IrelandHealth Research Institute, University of Limerick, Limerick, IrelandNorthern Sydney Local Health District, The Kolling Research Institute and Faculty of Health Sciences, The University of Sydney, St. Leonards, NSW, AustraliaDepartment of Physical Therapy and Human Movement Sciences, Feinberg School of Medicine, Northwestern University, Chicago, IL, United StatesLaboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, ChileLaboratorio de Neurobiología, Facultad de Ciencias de la Salud, Universidad San Sebastián, Concepción, ChileResearch and Development Department, Bay Pines VA Healthcare System, Bay Pines, FL, United StatesFear memory extinction (FE) is an important therapeutic goal for Posttraumatic stress disorder (PTSD). Cotinine facilitates FE in rodents, in part due to its inhibitory effect on the amygdala by the glutamatergic projections from the medial prefrontal cortex (mPFC). The cellular and behavioral effects of infusing cotinine into the mPFC on FE, astroglia survival, and the expression of bone morphogenetic proteins (BMP) 2 and 8, were assessed in C57BL/6 conditioned male mice. The role of the α4β2- and α7 nicotinic acetylcholine receptors (nAChRs) on cotinine’s actions were also investigated. Cotinine infused into the mPFC enhanced contextual FE and decreased BMP8 expression by a mechanism dependent on the α7nAChRs. In addition, cotinine increased BMP2 expression and prevented the loss of GFAP + astrocytes in a form independent on the α7nAChRs but dependent on the α4β2 nAChRs. This evidence suggests that cotinine exerts its effect on FE by modulating nAChRs signaling in the brain.https://www.frontiersin.org/article/10.3389/fphar.2020.00303/fullfear conditioningbone morphogenetic proteinsprefrontal cortexcholinergic receptorsMLA |
| spellingShingle | Patricia Oliveros-Matus Nelson Perez-Urrutia Nathalie Alvarez-Ricartes Florencia Echeverria George E. Barreto George E. Barreto James Elliott James Elliott Alexandre Iarkov Valentina Echeverria Valentina Echeverria Cotinine Enhances Fear Extinction and Astrocyte Survival by Mechanisms Involving the Nicotinic Acetylcholine Receptors Signaling Frontiers in Pharmacology fear conditioning bone morphogenetic proteins prefrontal cortex cholinergic receptors MLA |
| title | Cotinine Enhances Fear Extinction and Astrocyte Survival by Mechanisms Involving the Nicotinic Acetylcholine Receptors Signaling |
| title_full | Cotinine Enhances Fear Extinction and Astrocyte Survival by Mechanisms Involving the Nicotinic Acetylcholine Receptors Signaling |
| title_fullStr | Cotinine Enhances Fear Extinction and Astrocyte Survival by Mechanisms Involving the Nicotinic Acetylcholine Receptors Signaling |
| title_full_unstemmed | Cotinine Enhances Fear Extinction and Astrocyte Survival by Mechanisms Involving the Nicotinic Acetylcholine Receptors Signaling |
| title_short | Cotinine Enhances Fear Extinction and Astrocyte Survival by Mechanisms Involving the Nicotinic Acetylcholine Receptors Signaling |
| title_sort | cotinine enhances fear extinction and astrocyte survival by mechanisms involving the nicotinic acetylcholine receptors signaling |
| topic | fear conditioning bone morphogenetic proteins prefrontal cortex cholinergic receptors MLA |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00303/full |
| work_keys_str_mv | AT patriciaoliverosmatus cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling AT nelsonperezurrutia cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling AT nathaliealvarezricartes cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling AT florenciaecheverria cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling AT georgeebarreto cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling AT georgeebarreto cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling AT jameselliott cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling AT jameselliott cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling AT alexandreiarkov cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling AT valentinaecheverria cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling AT valentinaecheverria cotinineenhancesfearextinctionandastrocytesurvivalbymechanismsinvolvingthenicotinicacetylcholinereceptorssignaling |