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Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism.
Life Sci 2017; 173:43-54LS

Abstract

AIMS

To investigate the effect of FTY720 on the valproic acid (VPA) rat model of autism.

MAIN METHODS

As an animal model of autism, we used intraperitoneal injection of VPA on embryonic day 12.5 in Wistar rats. The pups were given FTY720 orally at doses of 0.25, 0.5 and 1mg/kg daily from postnatal day 15 to 35. Social behavior, spatial learning and memory were assessed at the end of FTY720 treatment. The histological change, oxidative stress, neuroinflammatory responses, and apoptosis-related proteins in the hippocampus were evaluated.

KEY FINDINGS

FTY720 (1mg/kg) administration to VPA-exposed rats (1) improved social behavior, spatial learning and memory impairment; (2) resulted in a reduction in neuronal loss and apoptosis of pyramidal cells in hippocampal CA1 regions; (3) inhibited activation of microglial cells, in turn lowering the level of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-6 in the hippocampus; (4) changed Malondialdehyde (MDA) levels, Glutathione (GSH) levels, superoxide dismutase (SOD) activity and Glutathione Peroxidase (GSH-Px) activity in the hippocampus; (6) inhibited the elevated Bax and caspase-3 protein levels and enhanced the relative expression level of Bcl-2 in the hippocampus; and (7) increased phospho-Ca2+/calmodulin-dependent protein kinase II (p-CaMKII), phospho-cAMP-response element binding protein (p-CREB) and Brain Derived Neurotrophic Factor (BDNF) protein expression in the hippocampus.

SIGNIFICANCE

FTY720 rescues social deficit, spatial learning and memory impairment in VPA-exposed rats. FTY720 exerts both a direct protection for neurons and an indirect modulation of inflammation-mediated neuron loss as a possible mechanism of neuroprotection.

Authors+Show Affiliations

Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.Department of Nursing, Harbin Medical University in Daqing, Daqing, Heilongjiang 163319, China.Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.Department of pediatrics, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China.Department of Pharmacology, Harbin Medical University in Daqing, Daqing, Heilongjiang 163319, China. Electronic address: 437343482@qq.com.Department of Child and Adolescent Health, School of Public Health, Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: wulijiehyd@126.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28161158

Citation

Wu, Hongmei, et al. "Fingolimod (FTY720) Attenuates Social Deficits, Learning and Memory Impairments, Neuronal Loss and Neuroinflammation in the Rat Model of Autism." Life Sciences, vol. 173, 2017, pp. 43-54.
Wu H, Wang X, Gao J, et al. Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism. Life Sci. 2017;173:43-54.
Wu, H., Wang, X., Gao, J., Liang, S., Hao, Y., Sun, C., ... Wu, L. (2017). Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism. Life Sciences, 173, pp. 43-54. doi:10.1016/j.lfs.2017.01.012.
Wu H, et al. Fingolimod (FTY720) Attenuates Social Deficits, Learning and Memory Impairments, Neuronal Loss and Neuroinflammation in the Rat Model of Autism. Life Sci. 2017 Mar 15;173:43-54. PubMed PMID: 28161158.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Fingolimod (FTY720) attenuates social deficits, learning and memory impairments, neuronal loss and neuroinflammation in the rat model of autism. AU - Wu,Hongmei, AU - Wang,Xuelai, AU - Gao,Jingquan, AU - Liang,Shuang, AU - Hao,Yanqiu, AU - Sun,Caihong, AU - Xia,Wei, AU - Cao,Yonggang, AU - Wu,Lijie, Y1 - 2017/02/01/ PY - 2016/12/01/received PY - 2017/01/23/revised PY - 2017/01/30/accepted PY - 2017/2/6/pubmed PY - 2017/3/16/medline PY - 2017/2/6/entrez KW - Autism spectrum disorder KW - Fingolimod (FTY720) KW - Hippocampal cell KW - Neuroinflammatory KW - Oxidative stress KW - VPA SP - 43 EP - 54 JF - Life sciences JO - Life Sci. VL - 173 N2 - AIMS: To investigate the effect of FTY720 on the valproic acid (VPA) rat model of autism. MAIN METHODS: As an animal model of autism, we used intraperitoneal injection of VPA on embryonic day 12.5 in Wistar rats. The pups were given FTY720 orally at doses of 0.25, 0.5 and 1mg/kg daily from postnatal day 15 to 35. Social behavior, spatial learning and memory were assessed at the end of FTY720 treatment. The histological change, oxidative stress, neuroinflammatory responses, and apoptosis-related proteins in the hippocampus were evaluated. KEY FINDINGS: FTY720 (1mg/kg) administration to VPA-exposed rats (1) improved social behavior, spatial learning and memory impairment; (2) resulted in a reduction in neuronal loss and apoptosis of pyramidal cells in hippocampal CA1 regions; (3) inhibited activation of microglial cells, in turn lowering the level of pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-6 in the hippocampus; (4) changed Malondialdehyde (MDA) levels, Glutathione (GSH) levels, superoxide dismutase (SOD) activity and Glutathione Peroxidase (GSH-Px) activity in the hippocampus; (6) inhibited the elevated Bax and caspase-3 protein levels and enhanced the relative expression level of Bcl-2 in the hippocampus; and (7) increased phospho-Ca2+/calmodulin-dependent protein kinase II (p-CaMKII), phospho-cAMP-response element binding protein (p-CREB) and Brain Derived Neurotrophic Factor (BDNF) protein expression in the hippocampus. SIGNIFICANCE: FTY720 rescues social deficit, spatial learning and memory impairment in VPA-exposed rats. FTY720 exerts both a direct protection for neurons and an indirect modulation of inflammation-mediated neuron loss as a possible mechanism of neuroprotection. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/28161158/Fingolimod__FTY720__attenuates_social_deficits_learning_and_memory_impairments_neuronal_loss_and_neuroinflammation_in_the_rat_model_of_autism_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(17)30036-X DB - PRIME DP - Unbound Medicine ER -