RÉSUMÉ
OBJECTIVES: Several recent studies have suggested that the physiopathology of bipolar disorder (BD) is related to immune system alterations and inflammation. Lithium (Li) is a mood stabilizer that is considered the first-line treatment for this mood disorder. The goal of the present study was to investigate the effects of Li administration on behavior and cytokine levels [interleukin (IL)-1ß, IL-4, IL-6, IL-10, and tumor necrosis factor-alpha (TNF-α)] in the periphery and brains of rats subjected to an animal model of mania induced by amphetamine (d-AMPH). METHODS: Male Wistar rats were treated with d-AMPH or saline (Sal) for 14 days; on Day 8 of treatment, the rats were administered Li or Sal for the final seven days. Cytokine (IL-1ß, IL-4, IL-6, IL-10, and TNF-α) levels were evaluated in the cerebrospinal fluid (CSF), serum, frontal cortex, striatum, and hippocampus. RESULTS: The present study showed that d-AMPH induced hyperactivity in rats (p < 0.001), and Li treatment reversed this behavioral alteration (p < 0.001). In addition, d-AMPH increased the levels of IL-4, IL-6, IL-10, and TNF-α in the frontal cortex (p < 0.001), striatum (p < 0.001), and serum (p < 0.001), and treatment with Li reversed these cytokine alterations (p < 0.001). CONCLUSIONS: Li modulates peripheral and cerebral cytokine production in an animal model of mania induced by d-AMPH, suggesting that its action on the inflammatory system may contribute to its therapeutic efficacy.
Sujet(s)
Antimaniacodépressifs/pharmacologie , Comportement animal/effets des médicaments et des substances chimiques , Trouble bipolaire/immunologie , Encéphale/effets des médicaments et des substances chimiques , Cytokines/effets des médicaments et des substances chimiques , Composés du lithium/pharmacologie , Activité motrice/effets des médicaments et des substances chimiques , Animaux , Antimaniacodépressifs/usage thérapeutique , Trouble bipolaire/induit chimiquement , Trouble bipolaire/traitement médicamenteux , Encéphale/immunologie , Stimulants du système nerveux central/toxicité , Cytokines/liquide cérébrospinal , Cytokines/immunologie , Dexamfétamine/toxicité , Modèles animaux de maladie humaine , Lobe frontal/effets des médicaments et des substances chimiques , Lobe frontal/immunologie , Hippocampe/effets des médicaments et des substances chimiques , Hippocampe/immunologie , Hypercinésie/induit chimiquement , Hypercinésie/traitement médicamenteux , Hypercinésie/immunologie , Interleukine-10/liquide cérébrospinal , Interleukine-10/immunologie , Interleukine-1 bêta/liquide cérébrospinal , Interleukine-1 bêta/effets des médicaments et des substances chimiques , Interleukine-1 bêta/immunologie , Interleukine-4/liquide cérébrospinal , Interleukine-4/immunologie , Interleukine-6/liquide cérébrospinal , Interleukine-6/immunologie , Composés du lithium/usage thérapeutique , Mâle , Activité motrice/immunologie , Néostriatum/effets des médicaments et des substances chimiques , Néostriatum/immunologie , Rats , Rat Wistar , Facteur de nécrose tumorale alpha/liquide cérébrospinal , Facteur de nécrose tumorale alpha/effets des médicaments et des substances chimiques , Facteur de nécrose tumorale alpha/immunologieRÉSUMÉ
Rabies has been an enigmatic disease of the nervous system because microscopic findings in the brain tissue are not paralleled by the severity of the clinical illness. The calcium binding protein calbindin (CB) is a neuronal marker of great interest in neuroanatomy and neuropathology. CB-ir neurons in the striatum and cerebral cortex are gabaergic cells. In the present work CB-immunoreactivity was evaluated in brains of normal and rabies-infected mice. Rabies infection caused loss of CB-immunostaining in the cortical supragranular layers as well as in the striatum. Loss of CB in the brains of mice infected with rabies virus can produce impairment in Ca++ homeostasis and in the gabaergic neurotransmission.