Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model
Abstract Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponecti...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Nature Portfolio
2024-01-01
|
Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-023-50503-8 |
_version_ | 1797363317459648512 |
---|---|
author | Manisha Samad Joakim Ek Stina Börchers Jean-Philippe Krieger Elisabet Stener-Victorin Karolina P. Skibicka Ingrid Wernstedt Asterholm Anna Benrick |
author_facet | Manisha Samad Joakim Ek Stina Börchers Jean-Philippe Krieger Elisabet Stener-Victorin Karolina P. Skibicka Ingrid Wernstedt Asterholm Anna Benrick |
author_sort | Manisha Samad |
collection | DOAJ |
description | Abstract Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects. |
first_indexed | 2024-03-08T16:19:43Z |
format | Article |
id | doaj.art-a18c7a1e1c5a4512a7b938a427780b96 |
institution | Directory Open Access Journal |
issn | 2045-2322 |
language | English |
last_indexed | 2024-03-08T16:19:43Z |
publishDate | 2024-01-01 |
publisher | Nature Portfolio |
record_format | Article |
series | Scientific Reports |
spelling | doaj.art-a18c7a1e1c5a4512a7b938a427780b962024-01-07T12:27:06ZengNature PortfolioScientific Reports2045-23222024-01-011411810.1038/s41598-023-50503-8Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse modelManisha Samad0Joakim Ek1Stina Börchers2Jean-Philippe Krieger3Elisabet Stener-Victorin4Karolina P. Skibicka5Ingrid Wernstedt Asterholm6Anna Benrick7Department of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Physiology and Pharmacology, Karolinska InstituteDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgDepartment of Physiology, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of GothenburgAbstract Polycystic ovary syndrome (PCOS) is associated with symptoms of moderate to severe anxiety and depression. Hyperandrogenism is a key feature together with lower levels of the adipocyte hormone adiponectin. Androgen exposure leads to anxiety-like behavior in female offspring while adiponectin is reported to be anxiolytic. Here we test the hypothesis that elevated adiponectin levels protect against the development of androgen-induced anxiety-like behavior. Pregnant mice overexpressing adiponectin (APNtg) and wildtypes were injected with vehicle or dihydrotestosterone to induce prenatal androgenization (PNA) in the offspring. Metabolic profiling and behavioral tests were performed in 4-month-old female offspring. PNA offspring spent more time in the closed arms of the elevated plus maze, indicating anxiety-like behavior. Intriguingly, neither maternal nor offspring adiponectin overexpression prevented an anxiety-like behavior in PNA-exposed offspring. However, adiponectin overexpression in dams had metabolic imprinting effects, shown as lower fat mass and glucose levels in their offspring. While serum adiponectin levels were elevated in APNtg mice, cerebrospinal fluid levels were similar between genotypes. Adiponectin overexpression improved metabolic functions but did not elicit anxiolytic effects in PNA-exposed offspring. These observations might be attributed to increased circulating but unchanged cerebrospinal fluid adiponectin levels in APNtg mice. Thus, increased adiponectin levels in the brain are likely needed to stimulate anxiolytic effects.https://doi.org/10.1038/s41598-023-50503-8 |
spellingShingle | Manisha Samad Joakim Ek Stina Börchers Jean-Philippe Krieger Elisabet Stener-Victorin Karolina P. Skibicka Ingrid Wernstedt Asterholm Anna Benrick Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model Scientific Reports |
title | Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model |
title_full | Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model |
title_fullStr | Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model |
title_full_unstemmed | Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model |
title_short | Elevated circulating adiponectin levels do not prevent anxiety-like behavior in a PCOS-like mouse model |
title_sort | elevated circulating adiponectin levels do not prevent anxiety like behavior in a pcos like mouse model |
url | https://doi.org/10.1038/s41598-023-50503-8 |
work_keys_str_mv | AT manishasamad elevatedcirculatingadiponectinlevelsdonotpreventanxietylikebehaviorinapcoslikemousemodel AT joakimek elevatedcirculatingadiponectinlevelsdonotpreventanxietylikebehaviorinapcoslikemousemodel AT stinaborchers elevatedcirculatingadiponectinlevelsdonotpreventanxietylikebehaviorinapcoslikemousemodel AT jeanphilippekrieger elevatedcirculatingadiponectinlevelsdonotpreventanxietylikebehaviorinapcoslikemousemodel AT elisabetstenervictorin elevatedcirculatingadiponectinlevelsdonotpreventanxietylikebehaviorinapcoslikemousemodel AT karolinapskibicka elevatedcirculatingadiponectinlevelsdonotpreventanxietylikebehaviorinapcoslikemousemodel AT ingridwernstedtasterholm elevatedcirculatingadiponectinlevelsdonotpreventanxietylikebehaviorinapcoslikemousemodel AT annabenrick elevatedcirculatingadiponectinlevelsdonotpreventanxietylikebehaviorinapcoslikemousemodel |