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


CONCLUSIONS
Our findings revealed a novel role of the satiating hormone amylin in promoting neurogenesis in the AP of adult rats.
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.
Claudia G
CG
Liberini
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.
Tito
T
Borner
Institute of Veterinary Physiology, Vetsuisse Faculty University of Zurich (UZH), 8057 Zurich, Switzerland. Electronic address: boyle@vetphys.uzh.ch.
Christina N
CN
Boyle
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.
Thomas A
TA
Lutz
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
J Neurosci Res. 2013 Jun;91(6):757-70
23526379
Physiol Behav. 1995 Dec;58(6):1197-202
8623020
Neuron. 2008 Jun 12;58(5):708-19
18549783
Cell. 2008 Feb 22;132(4):645-60
18295581
Nat Neurosci. 2009 Sep;12(9):1090-2
19701197
J Neuropathol Exp Neurol. 2014 Aug;73(8):734-46
25003234
Metabolism. 1997 Jan;46(1):67-70
9005972
Mol Pharmacol. 1999 Jul;56(1):235-42
10385705
J Neurosci. 2003 Nov 12;23(32):10411-8
14614100
Dev Growth Differ. 2006 Oct;48(8):513-23
17026715
Front Neuroendocrinol. 1994 Dec;15(4):301-20
7895890
Eur J Neurosci. 2016 Mar;43(5):653-61
26750109
J Neurosci. 2012 Jan 25;32(4):1244-52
22279209
Cell Metab. 2013 Apr 2;17(4):607-17
23562080
Eur J Neurosci. 2014 Oct;40(7):3055-66
25040689
Cell. 1999 Jun 11;97(6):703-16
10380923
Int J Obes Relat Metab Disord. 2001 Jul;25(7):1005-11
11443499
Neuron. 2005 Sep 15;47(6):803-15
16157276
Science. 2005 Oct 28;310(5748):679-83
16254185
Psychoneuroendocrinology. 2015 Jan;51:431-9
25462915
Nat Neurosci. 2009 Sep;12(9):1079-81
19710645
Forum Nutr. 2010;63:64-74
19955774
FEBS Lett. 2002 Sep 25;528(1-3):241-5
12297313
J Neurosci. 2011 Jan 19;31(3):1149-55
21248139
Aging (Albany NY). 2013 May;5(5):332-4
23667132
Mol Cell Neurosci. 2009 Jul;41(3):337-47
19409493
Diabetologia. 1995 Jun;38(6):642-8
7672483
Nat Neurosci. 2009 Sep;12(9):1097-105
19701198
Nat Neurosci. 2012 Mar 25;15(5):700-2
22446882
Physiol Behav. 1994 May;55(5):891-5
8022910
Endocrinology. 2010 Dec;151(12):5657-68
20962049
Neurobiol Dis. 2015 Feb;74:229-39
25484283
Br J Pharmacol. 2013 Dec;170(8):1459-581
24517644
Novartis Found Symp. 2000;231:220-35; discussion 235-41, 302-6
11131541
Am J Physiol Regul Integr Comp Physiol. 2010 Jun;298(6):R1475-84
20357016
Eur J Neurosci. 2014 Jun;39(11):1845-65
24628861
J Biol Chem. 2008 Jun 27;283(26):18238-47
18367451
Brain Res. 2000 Dec 15;886(1-2):47-53
11119686
Nature. 1998 May 28;393(6683):333-9
9620797
Proc Natl Acad Sci U S A. 2010 Jan 19;107(3):1201-6
20080708
Am J Physiol Regul Integr Comp Physiol. 2012 Feb 1;302(3):R340-51
22129618
Nat Med. 1998 Nov;4(11):1313-7
9809557
Peptides. 1998;19(9):1533-40
9864060
Neurobiol Aging. 2014 Apr;35(4):793-801
24239383
Physiol Behav. 2006 Nov 30;89(4):465-71
16697020