Antidepressant activity of fingolimod in mice

نویسندگان

  • Luigi di Nuzzo
  • Rosamaria Orlando
  • Cristina Tognoli
  • Paola Di Pietro
  • Giuseppe Bertini
  • Jessica Miele
  • Domenico Bucci
  • Marta Motolese
  • Sergio Scaccianoce
  • Alessandra Caruso
  • Gianluca Mauro
  • Carmine De Lucia
  • Giuseppe Battaglia
  • Valeria Bruno
  • Paolo Francesco Fabene
  • Ferdinando Nicoletti
چکیده

Recent findings indicate that fingolimod, the first oral drug approved for the treatment of multiple sclerosis (MS), acts as a direct inhibitor of histone deacetylases (HDACs) and enhances the production of brain-derived neurotrophic factor (BDNF) in the CNS. Both mechanisms are relevant to the pathophysiology and treatment of major depression. We examined the antidepressant activity of fingolimod in mice subjected to chronic unpredictable stress (CUS), a model of reactive depression endowed with face and pharmacological validity. Chronic treatment with fingolimod (3 mg kg(-1), i.p., once a day for 4 weeks) reduced the immobility time in the forced swim test (FST) in a large proportion of CUS mice. This treatment also caused anxiogenic-like effects in the social interaction test without affecting anxiety-like behavior in the elevated plus maze or spatial learning in the water maze. CUS mice showed reduced BDNF levels and enhanced HDAC2 levels in the hippocampus. These changes were reversed by fingolimod exclusively in mice that showed a behavioral response to the drug in the FST. Fingolimod treatment also enhanced H3 histone K14-acetylation and adult neurogenesis in the hippocampus of CUS mice. Fingolimod did not affect most of the parameters we have tested in unstressed control mice. The antidepressant-like activity of fingolimod was confirmed in mice chronically treated with corticosterone. These findings show for the first time that fingolimod exerts antidepressant-like effect acting in a "disease-dependent" manner, and raise the interesting possibility that the drug could relieve depressive symptoms in MS patients independently of its disease-modifying effect on MS.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Behavioral and Biochemical Evidences for Antidepressant-Like Activity of Celastrus Paniculatus Seed Oil in Mice

Introduction: Celastrus paniculatus seed oil, commonly known as Malkangni or Jyotishmati, was in use from time immemorial to treat brain related disorders. Celastrus paniculatus seed oil has significant antidepressant-like activity in chronic unpredictable stressed mice. The present study was undertaken to evaluate the antidepressant-like effect of Celastrus paniculatus seed oil ...

متن کامل

Evaluation of the antidepressant-like effects of acute and sub-acute administration of crocin and crocetin in mice

Objective: The present study was designed to investigate the putative antidepressant effects of crocin and crocetin, two major active ingredients of Crocus sativus L. (saffron) using mice in two different regimens of acute and sub-acute administration. Material and Methods: In acute treatment, antidepressant-like activities of crocin and crocetin (10, 20 and 40 mg/kg, i.p.) were evaluated using...

متن کامل

Evaluation of antidepressant-like effects of aqueous and ethanolic extracts of Pimpinella anisum fruit in mice

Objective: Pimpinella anisum (P. anisum) has different pharmacological properties such as anticonvulsant, analgesic, tranquilizer, antidepressant and anti-anxiety effects. In this study the antidepressant-like effect of aqueous and ethanolic extracts of P. anisum fruit in mice was investigated. Materials and Methods: Forced swimming test (FST) and tail suspension test (TST) were used to determ...

متن کامل

Evaluation of the antidepressant effects of pioglitazone in ovariectomized mice through nitric oxide pathway

Background: Pioglitazone is the selective PPAR-γ receptor agonist, which is prescribed for the treatment of type 2 diabetes and may also have antidepressant effects. Nitric oxide (NO) has been involved in some crucial roles, including learning, cognition and neurogenesis as well as some neurodegenerative diseases, including Parkinson, Alzheimer's disease (AD) and depression. Reduced estrogen le...

متن کامل

Antidepressant activity of methanol stem bark extract of Ficus platyphylla Del (Moraceae) in mice

Background & Aim: Depression is a heterogeneous mood disorder affecting both people in developing and developed countries. The drugs used in its management are associated with adverse effects and delayed response which compromise their therapeutic benefits. This makes it worthwhile to look for antidepressants plants with proven advantage and favourable benefit-...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2015