Efferent projections of neuropeptide Y‐expressing neurons of the dorsomedial hypothalamus in chronic hyperphagic models

Nov 23, 2012The Journal of comparative neurology

Output pathways of hunger-related neurons in the brain's energy control center in chronic overeating models

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Abstract

NPY expression in the DMH is significantly increased during chronic hyperphagic conditions such as lactation and diet-induced obesity.

DMH-NPY neurons project primarily to various hypothalamic regions, including the paraventricular nucleus and lateral hypothalamus.
In lactating rats, projections from DMH-NPY neurons are closely associated with CART-expressing neurons in specific hypothalamic areas.
DMH neurons project to the rostral raphe pallidus, but these projections do not contain NPY.
Most fibers in the rostral raphe pallidus are positive for orexin, indicating a different signaling pathway.
DMH-NPY projections were not found in the nucleus of the solitary tract, a region important for sympathetic regulation.

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The dorsomedial hypothalamus (DMH) has long been implicated in feeding behavior and thermogenesis. The DMH contains orexigenic neuropeptide Y (NPY) neurons, but the role of these neurons in the control of energy homeostasis is not well understood. NPY expression in the DMH is low under normal conditions in adult rodents but is significantly increased during chronic hyperphagic conditions such as lactation and diet-induced obesity (DIO). To understand better the role of DMH-NPY neurons, we characterized the efferent projections of DMH-NPY neurons using the anterograde tracer biotinylated dextran amine (BDA) in lactating rats and DIO mice. In both models, BDA- and NPY-colabeled fibers were limited mainly to the hypothalamus, including the paraventricular nucleus of the hypothalamus (PVH), lateral hypothalamus/perifornical area (LH/PFA), and anteroventral periventricular nucleus (AVPV). Specifically in lactating rats, BDA-and NPY-colabeled axonal swellings were in close apposition to cocaine- and amphetamine-regulated transcript (CART)-expressing neurons in the PVH and AVPV. Although the DMH neurons project to the rostral raphe pallidus (rRPa), these projections did not contain NPY immunoreactivity in either the lactating rat or the DIO mouse. Instead, the majority of BDA-labeled fibers in the rRPa were orexin positive. Furthermore, DMH-NPY projections were not observed within the nucleus of the solitary tract (NTS), another brainstem site critical for the regulation of sympathetic outflow. The present data suggest that NPY expression in the DMH during chronic hyperphagic conditions plays important roles in feeding behavior and thermogenesis by modulating neuronal functions within the hypothalamus, but not in the brainstem.

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Efferent projections of neuropeptide Y‐expressing neurons of the dorsomedial hypothalamus in chronic hyperphagic models

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