PUBLICATION

Habenular Kiss1 Neurons Modulate the Serotonergic System in the Brain of Zebrafish

Authors
Ogawa, S., Ng, K.W., Ramadasan, P.N., Nathan, F.M., and Parhar, I.S.
ID
ZDB-PUB-120329-11
Date
2012
Source
Endocrinology   153(5): 2398-2407 (Journal)
Registered Authors
Ogawa, Satoshi
Keywords
none
MeSH Terms
  • Animals
  • Brain/drug effects
  • Brain/metabolism*
  • Female
  • Habenula/drug effects
  • Habenula/metabolism*
  • Kisspeptins/metabolism*
  • Kisspeptins/pharmacology
  • Proto-Oncogene Proteins c-fos/metabolism
  • Raphe Nuclei/drug effects
  • Raphe Nuclei/metabolism
  • Receptors, G-Protein-Coupled/metabolism*
  • Serotonergic Neurons/drug effects
  • Serotonergic Neurons/metabolism*
  • Zebrafish
  • Zebrafish Proteins/metabolism*
  • Zebrafish Proteins/pharmacology
PubMed
22454151 Full text @ Endocrinology
Abstract

The Kiss1/KISS1 gene has recently been implicated as a potent hypothalamic regulator of reproductive functions, in particular, the onset of puberty in mammals. In zebrafish (Danio rerio), there are two kiss1 homologues (kiss1 and kiss2) expressed in the brain: Kiss2-expressing neurons in the hypothalamic nuclei are considered potent regulators of reproduction, whereas the role of Kiss1-expressing neurons in the habenula remains unknown. We first analyzed the expression of kiss1 mRNA in a transgenic zebrafish, in which the habenula-interpeduncular nucleus (IPN) pathway is labelled with green fluorescent protein, and our application of a biocytin neural tracer into the habenula showed the presence of neuronal projections of Kiss1 neurons to the ventral IPN. Therefore, we speculated that kiss1 neurons might regulate the serotonergic system in the raphe. However, laser microdissection followed by real-time PCR revealed the expression of Kiss1 receptor (kissr1) mRNA in the habenula and the ventral IPN but not in the dorsal IPN or the serotonergic neurons in the raphe nuclei. Dual-fluorescent in situ hybridization revealed the coexpression of kiss1 and kissr1 mRNA in the habenula. Administration of Kiss1 significantly decreased the level of kiss1 mRNA (0.3- to 0.5-fold, P < 0.001), but the level of c-fos mRNA was increased (<3-fold, P < 0.05) in the ventral habenula, suggesting that there is autocrine regulation of the kiss1 gene. Kiss1 administration significantly increased the c-fos mRNA levels in the raphe nuclei (2.5-fold, P < 0.001) and genes involved in the regulation of serotonin levels (pet1 and slc6a4a; 3.3- and 2.2-fold, P < 0.01). These findings suggest that the autocrine-regulated habenular Kiss1 neurons indirectly regulate the serotonergic system in the raphe nuclei through the IPN in the zebrafish.

Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping