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The immunological impairment of arcuate neuropeptide Y neurons by ricin A chain produces persistent decrease of food intake and body weight
Ist Teil von
Neuroscience, 1995-05, Vol.66 (1), p.151-159
Ort / Verlag
Oxford: Elsevier Ltd
Erscheinungsjahr
1995
Quelle
Elsevier Journal Backfiles on ScienceDirect (DFG Nationallizenzen)
Beschreibungen/Notizen
Neuropeptide Y is demonstrated as a potent orexigenic peptide when injected into the rat hypothalamic paraventricular nuclei. The neuropeptide Y innervation of paraventricular nuclei originates from both hypothalamic arcuate nuclei and brainstem neurons, whose specific role in the control of food intake is still under discussion. To assess the role of the arcuate neuropeptide Y in the regulation of food intake, we propose a new method for immunologically impairing the neuronal secretion of neuropeptide Y from a unique brain site.
The monoclonal antibody to the neuropeptide Y precursor epitope, the C-flanking peptide, was microinjected with two cellular toxins (the ricin A and the monensin) into the hypothalamic arcuate nuclei or paraventricular nuclei. One microinjection into the arcuate nuclei reduced the food intake and body weight gain for 10 days. It prevented the food intake stimulation usually induced by a 12 h food deprivation. This decrease of food intake was not due to the aversive properties of monoclonal antibody or cellular toxins, or the immunoneutralization of the biologically active neuropeptide Y, because (i) the acute effect of the microinjection into the arcuate nuclei promoted a transient increase of the food intake likely induced by a strong release of neuropeptide Y from the arcuate neurons which were immunologically damaged, and (ii) the C-flanking peptide monoclonal antibody binds neither neuropeptide Y nor its receptors. The microinjection was inefficient when C-flanking peptide monoclonal antibody was replaced by non-specific rat immunoglobulins or when the C-flanking peptide monoclonal antibody/toxins mixture was injected into the paraventricular nuclei.
The data bring further arguments in two domains. In the food intake regulation, our data confirm the major role of the hypothalamic arcuate nuclei in providing neuropeptide Y afferents to the paraventricular nuclei. On the other hand, cellular toxins can be immunologically introduced into peptidergic neurons with an antibody unable to interact with biologically active peptide. This offers a new approach to inhibiting the secretion of a central neuropeptide.