Article ; Online: Sex-specific disruption of murine midbrain astrocytic and dopaminergic developmental trajectories following antenatal GC treatment.
2015 Volume 221, Issue 5, Page(s) 2459–2475
Abstract: The mammalian midbrain dopaminergic systems arising in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are critical for coping behaviours and are implicated in neuropsychiatric disorders where early life challenges comprise ... ...
| Abstract | The mammalian midbrain dopaminergic systems arising in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) are critical for coping behaviours and are implicated in neuropsychiatric disorders where early life challenges comprise significant risk factors. Here, we aimed to advance our hypothesis that glucocorticoids (GCs), recognised key players in neurobiological programming, target development within these systems, with a novel focus on the astrocytic population. Mice received antenatal GC treatment (AGT) by including the synthetic GC, dexamethasone, in the mothers' drinking water on gestational days 16-19; controls received normal drinking water. Analyses of regional shapes and volumes of the adult SNc and VTA demonstrated that AGT induced long-term, dose-dependent, structural changes that were accompanied by profound effects on astrocytes (doubling/tripling of numbers and/or density). Additionally, AGT induced long-term changes in the population size and distribution of SNc/VTA dopaminergic neurons, confirming and extending our previous observations made in rats. Furthermore, glial/neuronal structural remodelling was sexually dimorphic and depended on the AGT dose and sub-region of the SNc/VTA. Investigations within the neonatal brain revealed that these long-term organisational effects of AGT depend, at least in part, on targeting perinatal processes that determine astrocyte density and programmed cell death in dopaminergic neurons. Collectively, our characterisation of enduring, AGT-induced, sex-specific cytoarchitectural disturbances suggests novel mechanistic links for the strong association between early environmental challenge (inappropriate exposure to excess GCs) and vulnerability to developing aberrant behaviours in later life, with translational implications for dopamine-associated disorders (such as schizophrenia, ADHD, autism, depression), which typically show a sex bias. |
|||||
|---|---|---|---|---|---|---|
| MeSH term(s) | Animals ; Apoptosis/drug effects ; Astrocytes/drug effects ; Astrocytes/physiology ; Cell Count ; Dexamethasone/administration & dosage ; Dopaminergic Neurons/drug effects ; Dopaminergic Neurons/physiology ; Female ; Glucocorticoids/administration & dosage ; Male ; Mice ; Mice, Inbred C57BL ; Pars Compacta/drug effects ; Pars Compacta/growth & development ; Pars Compacta/metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects/physiopathology ; Sex Characteristics ; Tyrosine 3-Monooxygenase/metabolism ; Ventral Tegmental Area/drug effects ; Ventral Tegmental Area/growth & development ; Ventral Tegmental Area/metabolism | |||||
| Chemical Substances | Glucocorticoids ; Dexamethasone (7S5I7G3JQL) ; Tyrosine 3-Monooxygenase (EC 1.14.16.2) | |||||
| Language | English | |||||
| Publishing date | 2015-05-06 | |||||
| Publishing country | Germany | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 2273162-3 | |||||
| ISSN | 1863-2661 ; 1863-2653 | |||||
| ISSN (online) | 1863-2661 | |||||
| ISSN | 1863-2653 | |||||
| DOI | 10.1007/s00429-015-1049-0 | |||||
| Shelf mark |
|
|||||
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
Full text online
More links
Kategorien
In stock of ZB MED Cologne/Königswinter
| Ub I Zs.90: Show issues | Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG) |
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.