Journal article
The satiating hormone amylin enhances neurogenesis in the area postrema of adult rats.
- Liberini CG Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich (UZH), 8057 Zurich, Switzerland; Zurich Centre for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland; Zurich Centre for Clinical Studies, Vetsuisse Faculty University of Zurich, 8057 Zurich, Switzerland.
- Borner T Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich (UZH), 8057 Zurich, Switzerland; Zurich Centre for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland.
- Boyle CN Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich (UZH), 8057 Zurich, Switzerland. Electronic address: boyle@vetphys.uzh.ch.
- Lutz TA Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich (UZH), 8057 Zurich, Switzerland; Zurich Centre for Integrative Human Physiology (ZIHP), University of Zurich, 8057 Zurich, Switzerland.
- 2016-10-01
Published in:
- Molecular metabolism. - 2016
AP, area postrema
Adult neurogenesis
Amylin
Area postrema
BrdU
BrdU, 5′-bromo-2-deoxyuridine
CR, calretinin
CTR, calcitonin receptor
CVO, circumventricular organs
Circumventricular organs
ERK1/2, extracellular signal-regulated kinase 1 and 2
EphRs, ephrin receptors
FDR, false discovery rate
GO, gene ontology
ME, median eminence
NGS, next generation sequencing
NSC, neural stem cells
NeuroD, neuronal differentiation
NeuroD1, neuronal differentiation-1
RAMP, receptor activity-modifying protein
Wnt, Wingless-Type MMTV Integration Site Family
bHLH, basic helix-loop-helix
English
OBJECTIVE
Adult neurogenesis in the subgranular zone and subventricular zone is generally accepted, but its existence in other brain areas is still controversial. Circumventricular organs, such as the area postrema (AP) have recently been described as potential neurogenic niches in the adult brain. The AP is the major site of action of the satiating hormone amylin. Amylin has been shown to promote the formation of neuronal projections originating from the AP in neonatal rodents but the role of amylin in adult neurogenesis remains unknown.
METHODS
To test this, we first performed an RNA-sequencing of the AP of adult rats acutely injected with either amylin (20 μg/kg), amylin plus the amylin receptor antagonist AC187 (500 μg/kg) or vehicle. Second, animals were subcutaneously equipped with minipumps releasing either amylin (50 μg/kg/day) or vehicle for 3 weeks to assess cell proliferation and differentiation with the 5'-bromo-2-deoxyuridine (BrdU) technique.
RESULTS
Acute amylin injections affected genes involved in pathways and processes that control adult neurogenesis. Amylin consistently upregulated NeuroD1 transcript and protein in the adult AP, and this effect was blocked by the co-administration of AC187. Further, chronic amylin treatment increased the number of newly proliferated AP-cells and significantly promoted their differentiation into neurons rather than astrocytes.
CONCLUSION
Our findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats.
Adult neurogenesis in the subgranular zone and subventricular zone is generally accepted, but its existence in other brain areas is still controversial. Circumventricular organs, such as the area postrema (AP) have recently been described as potential neurogenic niches in the adult brain. The AP is the major site of action of the satiating hormone amylin. Amylin has been shown to promote the formation of neuronal projections originating from the AP in neonatal rodents but the role of amylin in adult neurogenesis remains unknown.
METHODS
To test this, we first performed an RNA-sequencing of the AP of adult rats acutely injected with either amylin (20 μg/kg), amylin plus the amylin receptor antagonist AC187 (500 μg/kg) or vehicle. Second, animals were subcutaneously equipped with minipumps releasing either amylin (50 μg/kg/day) or vehicle for 3 weeks to assess cell proliferation and differentiation with the 5'-bromo-2-deoxyuridine (BrdU) technique.
RESULTS
Acute amylin injections affected genes involved in pathways and processes that control adult neurogenesis. Amylin consistently upregulated NeuroD1 transcript and protein in the adult AP, and this effect was blocked by the co-administration of AC187. Further, chronic amylin treatment increased the number of newly proliferated AP-cells and significantly promoted their differentiation into neurons rather than astrocytes.
CONCLUSION
Our findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats.
- Language
-
- English
- Open access status
- gold
- Identifiers
-
- DOI 10.1016/j.molmet.2016.06.015
- PMID 27688997
- Persistent URL
- https://sonar.ch/global/documents/252434
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