Mack SO, Wu M, Xu G (2008) Chemoresponsiveness of the hypothalamic paraventricular nucleus (PVN) is influenced by neuropeptide Y. Neuroscience 2008 Abstracts 383.7/RR74. Society for Neuroscience, Washington, DC.
Summary: The hypothalamic paraventricular nucleus (PVN) initiates autonomic responses to stress and behavioral changes. Neuropeptide Y-containing neurons primarily from the arcuate nucleus and, to a lesser extent, from the brainstem innervate preautonomic oxytocin-containing neurons in the PVN. The role of the PVN in mediating the effects of NPY on energy balance has been studied extensively; however, whether NPY influences respiratory drive via the PVN is not known. Previously, we demonstrated that stimulation of the PVN modulates cardiorespiratory responses via oxytocinergic innervation of neurons in the rostral ventrolateral region of the medulla oblongata where rhythm generating neurons are located. In this study, we selectively lesioned neurons in the PVN bilaterally with neurotoxin neuropeptide Y-saporin (NPY-SAP; 50 ng/100 μl per side) or blank-saporin (control vehicle). Both groups of rats showed similar (P>0.05) increases in body weight gain and intake of food and water over an 8 week period after lesioning. Core body temperature, measured at the same time every day, was also similar for both groups (P>0.05). At 4 weeks post lesioning, NPY-SAP treatment had no effect (P>0.05) on respiratory frequency (fR), tidal volume (VT) and minute ventilation (VE ) in awake, unrestrained animals breathing room air. During exposure to a hypercapnic challenge (5% CO2) for 10 minutes, fR (135 ± 7 vs 114 ±5 breaths min-1) and VE (154 ±13 vs 114± 5 ml min-1 100g-1 ) for the treated animals were significantly elevated (P<0.05) above responses for the control rats. Tidal volume for the treated (1.1 ±0.06) and the control (1.0 ± 0.03) groups was not different (P>0.05). Sensitivity to CO2 with respect to fR in the treated animals reached a peak at 4 weeks and declined thereafter over the next 4 weeks. While there were no apparent changes in morphology or number of parvocellular oxytocin-containing neurons 4 weeks after lesioning, abnormal morphology and a significant (P<0.05) reduction in oxytocin immunoreactive cells were prominent by 8 weeks post treatment. These findings indicate that NPY plays a role in modulating the respiratory response to hypercapnic stress through oxytocin neurons in the PVN. Further studies are needed to determine whether alterations in this pathway may be involved in the onset of hypoventilation associated with obesity.
Related Products: NPY-SAP (Cat. #IT-28)