SEGREGATION OF THE INTRAHYPOTHALAMIC AND EXTRAHYPOTHALAMIC NEUROPEPTIDE-Y AND CATECHOLAMINERGIC INPUTS ON PARAVENTRICULAR NEURONS, INCLUDING THOSE PRODUCING THYROTROPIN-RELEASING-HORMONE
S. Diano et al., SEGREGATION OF THE INTRAHYPOTHALAMIC AND EXTRAHYPOTHALAMIC NEUROPEPTIDE-Y AND CATECHOLAMINERGIC INPUTS ON PARAVENTRICULAR NEURONS, INCLUDING THOSE PRODUCING THYROTROPIN-RELEASING-HORMONE, Regulatory peptides, 75-6, 1998, pp. 117-126
In fasting, declining circulating thyroid hormone levels coincide with
suppressed thyrotropin-releasing hormone (TRH) mRNA and peptide level
s and elevated NPY release and binding in the parvicellular paraventri
cular nucleus (PVN). It is suggested that NPY, in parallel with trigge
ring feeding behavior, interrupts normal thyroid feedback in food depr
ivation. To gain further insights into the involvement of NPY in the r
egulation of TRH cells, this study sought to elucidate the source of t
he NPY innervation of TRH neurons. The median forebrain bundle (MFB) t
hat carries the ascending NPY fibers from the brain stem catecholamine
rgic nuclei was unilaterally transected. Animals were sacrificed 2 and
5 days after surgery and double immunocytochemistry for NPY and TRH o
r tyrosine hydroxylase (TH) and TRH was performed on sections from the
PVN. Two days after the surgery, light microscopic examination reveal
ed no changes in the numbers of NPY boutons making putative contacts w
ith TRH cell bodies and proximal dendrites. On the other hand, under t
he electron microscope, NPY- and TH-immunoreactive fibers containing a
utophagous cytolysosomes, an early sign of catecholaminergic fiber deg
eneration, were found to establish asymmetric synapses on distal dendr
ites and dendritic spines of TRH-immunoreactive cells. However, the sa
me electron microscopic analysis did not reveal any degenerating NPY-i
mmunolabeled fibers in synaptic contact with TRH cell bodies and proxi
mal dendrites. Five days after the surgery, when NPY and TH immunoreac
tivities were no longer detected in the ipsilateral MFB, no decrease i
n the numbers of NPY and TH boutons on TRH cell bodies and proximal de
ndrites could be detected, when compared to the contralateral side. El
ectron microscopy revealed fibers with Wallerian degeneration establis
hing asymmetric synapses exclusively on the distal dendrites and spine
s of TRH neurons. In conclusion, this study demonstrated that the NPY
and catecholaminergic input on PVN TRH cells are of mixed origin. The
cell bodies and proximal dendrites of TRH neurons receive a robust, pu
tative inhibitory NPY input from the hypothalamus. The distal dendrite
s and dendritic spines of the TRH cells also receive a putative stimul
atory NPY input from the brain stem catecholaminergic neurons. It is s
uggested that because of its proximal location and abundance, NPY of h
ypothalamic origin exerts a tonic inhibition on PVN TRH cells that int
errupts negative thyroid feedback during food deprivation. Furthermore
, it is likely that a general inhibition and not stimulation of parvic
ellular PVN activity may underlie the triggering of feeding behavior b
y hypothalamic NPY. (C) 1998 Elsevier Science Ireland B.V. All rights
reserved.