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Neuroscience. 2003;119(4):1113-45.
Diencephalic neurons producing melanin-concentrating hormone are influenced by local and multiple extra-hypothalamic tachykininergic projections through the neurokinin 3 receptor.

Cvetkovic V, Poncet F, Fellmann D, Griffond B, Risold PY.

Laboratoire d'Histologie, Faculte de Medecine et de Pharmacie, Universite de Franche-Comte, Place St Jacques, 25030, Besancon, France.

As melanin-concentrating hormone (MCH) neurons express the neurokinin 3 receptor (NK3) in the rat diencephalon, their innervation by tachykininergic fibers, the origin of this innervation and the effect of a NK3 agonist on MCH mRNA expression were researched. The obtained results show that the tachykininergic system develops complex relationships with MCH neurons. Overall, MCH cell bodies appeared targeted by both NKB- and SP-inputs. These afferents have multiple hypothalamic and extra-hypothalamic origins, but a local (intra-lateral hypothalamic area) origin from small interneurons was suspected as well. MCH cell bodies do not express NK1, but around 2.7% of the MCH neurons contained SP after colchicine injection. Senktide, a NK3 agonist, produced an increase of the MCH mRNA expression in cultured hypothalamic slices. This effect was reversed by two NK3 antagonists. Tachykinins enhance MCH mRNA expression, and, thus, may modulate the effect of MCH in functions such as feeding and reproductive behaviors in which this peptide has been experimentally involved.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12831868&dopt=Abstract

Regul Pept. 2003 Jul 15;114(2-3):109-14.
Behavioural analysis of melanin-concentrating hormone in rats: evidence for orexigenic and anxiolytic properties.

Kela J, Salmi P, Rimondini-Giorgini R, Heilig M, Wahlestedt C.

Center for Genomics and Bioinformatics, Karolinska Institutet, Berzelius vag 35, SE-171 77 Stockholm, Sweden.

Melanin-concentrating hormone (MCH) is a cyclic neuropeptide, predominantly expressed in hypothalamus, and recognized as a key regulator in feeding behaviour and energy balance. In this study, we examined the behavioural effects of intracerebroventricularly administered MCH on food intake, anxiety, exploratory behaviour and body core temperature in rats. MCH (0.15-10.0 microg, i.c.v.) acutely increased food intake in a dose-dependent manner. In addition, MCH (0.6-10.0 microg, i.c.v.) produced effects similar to anxiolytics in an animal model of anxiety, Vogel's punished drinking test. Thus, punished drinking episodes were significantly increased. We found no effects of MCH (5.0-20.0 microg, i.c.v.) on locomotor activity either in habituated or non-habituated animals. Furthermore, MCH did not produce any changes in body core temperature. Together, these observations further support a role for MCH as an orexigenic neuropeptide and also suggest anti-anxiety properties for MCH.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12832098&dopt=Abstract [PubMed - in process]

Neurotox Res. 2003;5(1-2):35-44.
Neuromelanin and its interaction with iron as a potential risk factor for dopaminergic neurodegeneration underlying Parkinson's disease.

Gerlach M, Double KL, Ben-Shachar D, Zecca L, Youdim MB, Riederer P.

Clinical Neurochemistry, Department of Child and Youth Psychiatry and Psychotherapy, University of Wurzburg, Fuchsleinstrasse 15, D-97080 Wurzburg, Germany. manfred.gerlacail.uni-wuerzburg.de

Neuromelanin (NM) is a granular, dark brown pigment produced in some but not all of the dopaminergic neurons of the human substantia nigra (SN). In Parkinson's disease (PD) the pigmented dopaminergic neurons of the SN degenerate, suggesting that this process is related to the presence of NM. As yet it is unknown whether NM in the parkinsonian brain differs from that found in healthy tissue and thus may fulfil a different role within this tissue. The function of NM within the pigmented neurons is unknown but other melanins are believed to play a protective role via attenuation of free radical damage. Experimental evidence suggests that NM may also exhibit this characteristic, possibly by direct inactivation of free radical species or via its ability to chelate transition metals, such as iron. NM has the ability to bind a variety of metals, seven per cent of isolated NM is reported to consist of Fe, Cu, Zn and Cr. Iron is of particular interest as this metal is highly concentrated within the SN. Up to 20 per cent of the total iron contained in the SN from normal subjects is bound within NM. Further, it was demonstrated that NM contains a protein component and that iron is bound to NM in the ferric form. Increased tissue iron found in the parkinsonian SN may saturate iron-chelating sites on NM, and a looser association between iron and NM may result in an increased, rather than decreased, production of free radical species. It is hypothesized that this redox-active iron could be released and involved in a Fenton-like reaction leading to an increased production of oxidative radicals. The resultant radical-mediated cytotoxicity may contribute to cellular damage observed in PD.

online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12832223&dopt=Abstract [PubMed - in process]

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