Specific alteration of the expression of selected hypothalamic neuropeptides during acute and late mouse brain infection using a morbillivirus: relevance to the late-onset obesity?
Neurotropic viruses are involved in pathologies of the central nervous system, triggering transient or irreversible disorders, such as neurological diseases or homeostasis imbalance. In experimental animals, viruses have been shown to cause obesity, a complex disease depending on multiple factors, including genetic susceptibility and environmental components. Using a mouse model of virally induced obesity following brain infection by the Canine Distemper Virus (CDV), a morbillivirus closely related to the human measles virus, we investigated the modulation of expression of several hypothalamic neuropeptides known to intervene in the regulation of body weight and energy expenditure, both during the acute and late stages of infection. During the acute stage, while viral replication occurs, we found a dramatic decrease of expressions of neuropeptides, in particular neuropeptide Y, melanin-concentrating hormone (MCH), hypocretin, vasopressin and tachykinins, the magnitude of which seemed to be linked to the viral burden and the individual susceptibility. The effect of the virus, however, varied with the hypothalamic nucleus and neuropeptide involved, suggesting that certain circuits were affected while others remained intact. During the late stage of infection, marked recovery to the initial hypothalamic levels of peptide expression was seen in a number of lean animals, suggesting recovery of homeostasis equilibrium. Interestingly, some neuropeptidergic systems remained disturbed in mice exhibiting obese phenotype, arguing for their involvement in triggering/maintaining obesity. Even though our data could not fully explain the viral-induced obesity, they may be helpful in understanding the molecular events associated with obesity and in investigating therapeutic alternatives.
Griffond
Bernadette
B
Laboratoire d'Histologie, Faculté de Médecine, Place Saint-Jacques, 25030 Besançon Cedex, France. bernadette.griffond@univ-fcomte.fr
Verlaeten
Olivier
O
Belin
Marie-Françoise
MF
Risold
Pierre-Yves
PY
Bernard
Arlette
A
D000818:Animals; D002452:Cell Count / Q000379:methods; D004217:Distemper Virus, Canine / Q000472:pathogenicity; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D007028:Hypothalamic Hormones / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism* / Q000821:virology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008543:Melanins / Q000378:metabolism; D051379:Mice; D018185:Morbillivirus Infections / Q000209:etiology / Q000378:metabolism*; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D000068797:Orexins; D010907:Pituitary Hormones / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015320:Tachykinins / Q000378:metabolism; D013997:Time Factors; D014667:Vasopressins / Q000378:metabolism
D007028:Hypothalamic Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008543:Melanins; D009478:Neuropeptide Y; D009479:Neuropeptides; D000068797:Orexins; D010907:Pituitary Hormones; D012333:RNA, Messenger; D015320:Tachykinins; D014667:Vasopressins; C019463:melanin-concentrating hormone