title: Fingolimod (FTY720) improves hippocampal synaptic plasticity and memory deficit in rats following focal cerebral ischemia.
abstract: Fingolimod (FTY720) is a known sphingosine-1-phosphate (S1P) receptor agonist. Several studies have shown the therapeutic efficacy of FTY720 in neurodegenerative disorders. However, the neuroprotective mechanisms in brain ischemia have not been adequately studied. Therefore, the present study aimed to investigate the effects of FTY720 on the impairment of learning and memory and hippocampal synaptic plasticity induced by middle cerebral artery occlusion (MCAO) in ischemic brain injury. Twenty eight male rats were randomly divided into four groups of control (n=7), sham (n=8), ischemic-reperfusion+vehicle (I/R+V; n=7), and I/R+FTY720 (n=6). After 1h of the occlusion of artery, the filament was gently withdrawn to allow reperfusion for the next 7 days. The animals first received a dose of FTY720 (0.5mg/Kg) or its vehicle (intra-peritoneal) twenty-four hours before surgery in I/R+FTY720 and I/R+V groups, respectively. The administration of FTY720 or its vehicle continued every other day. The passive avoidance test and field potential recording were used for evaluation of learning, memory and synaptic plasticity. The brain infarct volume was measured by triphenyltetrazolim hydrochloride (TTC) staining. MCAO caused infarct damage in the rat's brain tissue. The administration of FTY720 significantly reduced the size of the lesion, improved the memory impairment of MCAO rats, and increased the STL time. In addition, the field potential recording demonstrated a marked reduction in induction of long-term potentiation of MCAO animals. However, administration of FTY720 recovers the magnitude of the LTP without any effects on presynaptic plasticity and neurotransmitter release probability. The results of this study demonstrated that MCAO in rats impairs the retention of passive avoidance tasks and multiple injection of FTY720 improved the memory performance after MCAO by LTP induction via post-synaptic mechanisms.
authors.affiliation: Department of physiology, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: nazari_290@yahoo.com.
authors.forename: Maryam
authors.initials: M
authors.lastname: Nazari
authors.affiliation: Department of physiology, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: keshavarso@sums.ac.ir.
authors.forename: Somaye
authors.initials: S
authors.lastname: Keshavarz
authors.affiliation: Department of physiology, Shiraz University of Medical Sciences, Shiraz, Iran; Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: arafati@sums.ac.ir.
authors.forename: Ali
authors.initials: A
authors.lastname: Rafati
authors.affiliation: Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: namavarm@sums.ac.ir.
authors.forename: Mohammad Reza
authors.initials: MR
authors.lastname: Namavar
authors.affiliation: Department of physiology, Shiraz University of Medical Sciences, Shiraz, Iran; Histomorphometry and Stereology Research Centre, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: haghani55@yahoo.com.
authors.forename: Masoud
authors.initials: M
authors.lastname: Haghani
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology; D004195:Disease Models, Animal; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use*; D051597:Hippocalcin / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology*; D017774:Long-Term Potentiation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy / Q000209:etiology*; D009460:Neurologic Examination; D009473:Neuronal Plasticity / Q000187:drug effects*; D009504:Neutrophils / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D051597:Hippocalcin; D000068876:Fingolimod Hydrochloride
keywords: FTY720; Fingolimod; LTP; Sphingosine-1-phosphate; Stroke