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1.
Eur J Pharmacol ; 667(1-3): 402-9, 2011 Sep 30.
Article in English | MEDLINE | ID: mdl-21514291

ABSTRACT

Epidemiological and experimental data indicate that maternal undernutrition may sensitize the offspring to the apparition of chronic diseases such as metabolic syndrome and schizophrenia, suggesting that these pathologies may have a developmental origin. To test this hypothesis, we have compared the effects of a 4 weeks treatment of clozapine (30 mg/kg once daily, p.o.) or aripiprazole (10 mg/kg once daily, p.o.) on metabolic and hormonal parameters in 4-month-old male animals from control or 70% prenatally food-restricted mothers (FR30 model). Both neuroleptics did not markedly modify body weight gain and food intake in both controls and FR30 rats. Clozapine decreased insulin secretion in both groups but significantly diminished leptin, corticosterone and glucose plasma levels only in FR30 animals. Aripiprazole decreased corticosterone plasma levels only in FR30 animals. Using quantitative RT-PCR array containing 84 obesity-related genes, we identified several genes involved in energy metabolism regulation whose expression was modified by clozapine or aripiprazole in adult male rat hypothalami. In addition, we demonstrated that expression of some of these genes was differentially affected by each neuroleptic in the hypothalamus of both FR30 and control animals. Although no marked metabolic alterations were observed in both control and FR30 animals after clozapine or aripiprazole treatment, our data indicate that offspring from undernourished mothers exhibit a modified sensitivity to atypical neuroleptics. Our results do not rule out a putative developmental origin of schizophrenia and may help to understand the way by which atypical neuroleptics, such as clozapine, sensitize schizophrenic patients to the development of metabolic disorders.


Subject(s)
Antipsychotic Agents/pharmacology , Clozapine/pharmacology , Malnutrition , Nervous System/growth & development , Piperazines/pharmacology , Prenatal Nutritional Physiological Phenomena , Quinolones/pharmacology , Schizophrenia/pathology , Animals , Aripiprazole , Body Weight/drug effects , Disease Susceptibility/chemically induced , Eating/drug effects , Female , Gene Expression Regulation/drug effects , Hormones/blood , Hypothalamus/drug effects , Hypothalamus/metabolism , Male , Nervous System/drug effects , Obesity/genetics , Pregnancy , Rats , Rats, Wistar , Schizophrenia/metabolism , Schizophrenia/physiopathology
2.
Neurosci Lett ; 414(3): 268-72, 2007 Mar 13.
Article in English | MEDLINE | ID: mdl-17240057

ABSTRACT

EM66 is a 66-amino acid peptide derived from secretogranin II, a member of granin acidic secretory protein family, by proteolytic processing. EM66 has been previously characterized in the jerboa (Jaculus orientalis) hypothalamus and its potential implication in the neuroendocrine regulation of feeding behaviour has been demonstrated. In the present study, an immunohistochemical analysis of the localization of EM66 within hypothalamic structures of rat was performed and compared to the distribution of EM66 in the jerboa hypothalamus. In the rat hypothalamus, as in the jerboa, EM66 immunostaining was detected in the parvocellular paraventricular, preoptic and arcuate nuclei, as well as the lateral hypothalamus which displayed an important density of EM66-producing neurones. However, unlike jerboa, the suprachiasmatic and supraoptic nuclei of the rat hypothalamus were devoid of cellular EM66-immunolabeling. Thus, the novel peptide EM66 may exert common neuroendocrine activities in rat and jerboa, e.g. control of food intake, and species-specific roles in jerboa such as the regulation of biological rhythms and hydromineral homeostasis. These results suggest the existence of differences between jerboas and rats in neuroendocrine regulatory mechanisms involving EM66.


Subject(s)
Hypothalamus/metabolism , Neuropeptides/metabolism , Peptide Fragments/metabolism , Rats, Wistar/metabolism , Rodentia/metabolism , Secretogranin II/metabolism , Animals , Brain Mapping , Feeding Behavior/physiology , Female , Homeostasis/physiology , Hypothalamus/anatomy & histology , Immunohistochemistry , Male , Neurons/metabolism , Neuropeptides/chemistry , Neurosecretory Systems/metabolism , Peptide Fragments/chemistry , Periodicity , Rats , Rats, Wistar/anatomy & histology , Rodentia/anatomy & histology , Secretogranin II/chemistry , Species Specificity , Water-Electrolyte Balance/physiology
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