Interactions Between Kisspeptins and Neurokinin B - Kisspeptin Signaling in Reproductive Biology - page 318

Fig. 15.1 Schematic representation of the TAC3 gene depicting the exon encoding NKB
acid residues in length that share a common carboxy-terminal amino acid sequence
(Phe-X-Gly-Leu-Met-NH 2 ), where X corresponds to an aliphatic (NKA and NKB)
or an aromatic (SP) residue [ 16 ]. The gene-encoding NKB ( TAC3 in higher primates
and Tac2 in rodents) is divided into seven exons, fi ve of which encode the precursor
preprotachykinin B [ 16 - 18 ]. Following proteolytic cleavage, this precursor leads to,
fi rst, proneurokinin B, and then NKB (initially contained in exon 5) (Fig. 15.1 ) [ 16 ].
The expression of NKB mRNA and protein displays a dispersed distribution in
the brain of all studied species to date. In humans, prominent populations of TAC3 -
positive neurons have been identifi ed in the infundibular nucleus, anterior hypotha-
lamic area, septal region, diagonal band of Broca, bed nucleus of the stria terminalis,
amygdala, and neocortex [ 19 , 20 ]. In the rat, Tac2 expression has been found in the
cerebral cortex, hippocampus, amygdaloid complex, bed nucleus of the stria termi-
nalis, ventral pallidum, habenula, olfactory bulb, dorsomedial nucleus, ventrome-
dial nucleus, lateral hypothalamic area (LHA), caudate-putamen, medial preoptic
area, arcuate nucleus (ARC), lateral mammillary bodies, superior colliculus, central
gray, and dorsal horn of the spinal cord (Fig. 15.2 ) [ 21 - 23 ]. Of note, mice display a
roughly similar distribution of Tac2 mRNA, although, unlike rats, mice express
Tac2 neither in the hippocampus nor in the nucleus of the lateral olfactory tract [ 24 ].
Immunohistochemistry studies depicting the distribution of NKB closely parallel
the neuroanatomical mapping of the gene transcript, and importantly, also offer
conclusive information on the localization of NKB fi bers, thus pointing to potential
areas of NKB action [ 25 - 31 ]. Focusing on the population of NKB neurons in the
ARC, projections from this nucleus have been described through a combination of
tract tracing and double labeling techniques with specifi c known co-transmitters of
NKB in this neuronal site (e.g., dynorphin and kisspeptin) [ 25 , 27 , 28 , 30 - 32 ]. NKB
fi bers have been found to form a dense network within the ARC and the median
eminence. From the ARC of the rat, NKB neurons branch to innervate rostral brain
areas, such as the magnocellular and parvocellular nucleus, the anteroventral peri-
ventricular nucleus (AVPV), preoptic area, septal nuclei, and the bed nucleus of the
stria terminalis [ 30 , 33 ]. In addition, NKB neurons have been shown to project
dorsally to the dorsomedial nucleus, periventricular nucleus, ventromedial nucleus,
and LHA, and also may extend caudally to the ventral premammillary nucleus [ 30 ].
Neurokinin 3 Receptor
Tachykinins bind a family of G-protein-coupled receptors (GPCRs)—including
neurokinin receptor 1 (NK1R), NK2R, and NK3R—to mediate their biological