title: Mice lacking chromogranins exhibit increased aggressive and depression-like behaviour.
abstract: Chromogranins are acidic proteins; both chromogranins A and B constitute the main protein component in the vesicular matrix of large dense core vesicles. Chromogranins are a natural source of peptides with different physiological activities that have been associated with vascular and neurological diseases. We have used three different genetic mutant models of mice lacking chromogranin A, chromogranin B and both all on the same C57BL/6J background, to characterize the physiological roles of these proteins using metabolic, cardiovascular and behavioural tests. In mice from 3 to 18 months of age, the lack of any chromogranin promoted age-dependent hypersensitivity to insulin, while the lack of both chromogranins provoked progressive lack of response to stress, as restriction did not promote tachycardia in old mice. Moreover, the lack of chromogranin B produced a depressive-like and aggressive phenotype, while the lack either or both chromogranins increased barbering behaviour. In addition, we observed no effects on light-dark box or RotaRod tests. Mice lacking chromogranin B exhibited lower exploratory activity. Based on this extensive phenotyping with more than 2800 mice, these findings support roles of chromogranins, or the peptides derived from them, in the control of aggressive behaviour along with changes in their metabolic profile beyond their previously described activities in the secretory pathway.
authors.affiliation: Pharmacology Unit, Medical School, University of La Laguna, Tenerife, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Pereda
authors.affiliation: Pharmacology Unit, Medical School, University of La Laguna, Tenerife, Spain.
authors.forename: Marta R
authors.initials: MR
authors.lastname: Pardo
authors.affiliation: Pharmacology Unit, Medical School, University of La Laguna, Tenerife, Spain.
authors.forename: Yezer
authors.initials: Y
authors.lastname: Morales
authors.affiliation: Pharmacology Unit, Medical School, University of La Laguna, Tenerife, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Dominguez
authors.affiliation: Pharmacology Unit, Medical School, University of La Laguna, Tenerife, Spain.
authors.forename: Maria Rosa
authors.initials: MR
authors.lastname: Arnau
authors.affiliation: Pharmacology Unit, Medical School, University of La Laguna, Tenerife, Spain. Electronic address: rborges@ull.es.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Borges
mesh_terms: D000221:Adaptation, Ocular / Q000235:genetics; D000367:Age Factors; D000374:Aggression / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000502:physiology; D001786:Blood Glucose / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D001823:Body Composition / Q000235:genetics; D002395:Catecholamines / Q000652:urine; D002864:Chromogranins / Q000235:genetics / Q000378:metabolism*; D003863:Depression / Q000235:genetics* / Q000503:physiopathology*; D005106:Exploratory Behavior / Q000502:physiology; D005260:Female; D006120:Grooming / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D013550:Swimming / Q000523:psychology; D013997:Time Factors
chemical_list: D001786:Blood Glucose; D002395:Catecholamines; D002864:Chromogranins
keywords: Behaviour; Chromogranin A; Chromogranin B; Glycaemia; Hypertension