Neuropeptide Y‐producing neurons of the arcuate nucleus regenerate axons after surgical deafferentation of the mediobasal hypothalamus

Abstract

Dorsolateral and ventomedial surgical deafferentation of the hypothalamus were used to study the capacity of different types of neuropeptide Y-containing axons afferent to the dorsal hypothalamus to regenerate through surgical lesions. The kinetics of the postlesional responses of transected neuropeptide Y-axons was studied on 30–40 μm thick vibratome sections, either (i) by light or electron microscopy after peroxidase immunostaining for neuropeptide Y or (ii) by confocal microscopy after double fluorescence immunostaining for neuropeptide Y and for glial fibrillary acidic protein. The dorsolateral cut was found to sever 2 main pathways containing neuropeptide Y axons located, respectively, below the bed nucleus of the stria terminalis and in the perifornical region. In both regions transected fibers were found to abut onto the surgical lesion, but even 45 days after the lesion, they were very rarely observed to penetrate into the astroglial scar formed along the lesion. The ventromedial cut was found to sever numerous neuropeptide axons that originate in the underlying arcuate nucleus. Seven to 15 days after the lesion neuropeptide Y fibers located below this type of cut presented a dramatic increase in both their numerical density and their immunostaining intensity. With increasing post-surgery times, an increased number of neuropeptide Y fibers was observed to penetrate and to cross the lesional scar formed by densely packed astrocytic processes. Electron microscope observations further demonstrated that 45 days after the lesion, numerous neuropeptide Y-immunoreactive axonal profiles were included in the scar matrix, which appeared to be mainly composed of closely interdigitating astrocytic processes containing dense bundles of filaments. These data indicate that, in contrast to other neuropeptide Y neurons innervating the dorsal hypothalamus, neuropeptide Y neurons of the arcuate nucleus regenerate axons through the astroglial scar produced by a surgical lesion placed in the ventromedial hypothalamus.