The satiating hormone amylin enhances neurogenesis in the area postrema of adult rats

Abstract

ObjectiveAdult 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.MethodsTo 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.ResultsAcute 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.ConclusionOur findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats.

Improvement of spatial learning and memory, cortical gyrification patterns and brain oxidative stress markers in diabetic rats treated with Ficus deltoidea leaf extract and vitexin

“…Clinical and animal studies have recently looked at the unique relationship between amylin and cognition. 88 , 89 Similar to the finding by Qiu, 90 the concentration of amylin was markedly decreased in the DC rats. It is worth mentioning that amylin hormone potently enhances the translocation of Aβ peptide from the brain into blood.…”

Islet Amyloid Polypeptide: A Partner in Crime With Aβ in the Pathology of Alzheimer's Disease

“…As the primary site of IAPP action, the area postrema (AP) is the brain structure best characterized in terms of IAPP effects. While IAPP was shown to promote the formation of AP neuronal projections in neonatal rodents, in adult Wistar rats, IAPP injections were reported (1) to affect genes controlling neurogenesis, particularly NeuroD1, (2) to increase the number of newly proliferated AP-cells, and (3) to promote differentiation of these cells into neurons (Liberini et al, 2016). A study to investigate the mechanism by which IAPP modulates neuronal excitability in AP neurons in rat brainstem slices revealed that IAPP induced changes in excitatory responses of neurons not displaying the hyperpolarization-activated cation current.…”

Endogenous amylin contributes to birth of microglial cells in arcuate nucleus of hypothalamus and area postrema during fetal development

“…The male mice were removed thereafter. Dams were injected twice 12 h apart with BrdU at E12 (75 mg/kg sc, Sigma Aldrich, Buchs, Switzerland) (22,23,30). The day of the birth was designated as P0.…”

“…The role of amylin as a neurogenic factor has been recently examined in adult rats; exogenous amylin, which was continuously infused in male adult rats for 4 wk, increased cell birth and favored neurogenesis in the AP (30). However, the neurogenic role of amylin during embryogenesis has never been assessed.…”