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Frequent spontaneous seizures followed by spatial working memory/anxiety deficits in mice lacking sphingosine 1-phosphate receptor 2
- Source :
- Epilepsy & Behavior. 22:659-665
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- The diverse physiological effects of sphingosine 1-phosphate (S1P) are mostly mediated by its five cognate G protein-coupled receptors, S1P(1)-S1P(5), which have attracted much attention as future drug targets. To gain insight into S1P(2)-mediated signaling, we analyzed frequent spontaneous seizures in S1P(2)-deficient (S1P(2)(-/-)) mice obtained after several backcrosses onto a C57BL/6N background. Full-time video recording of 120 S1P(2)(-/-) mice identified 420 seizures both day and night between postnatal days 25 and 45, which were accompanied by high-voltage synchronized cortical discharges and a series of typical episodes: wild run, tonic-clonic convulsion, freezing, and, occasionally, death. Nearly 40% of 224 S1P(2)(-/-) mice died after such seizures, while the remaining 60% of the mice survived to adulthood; however, approximately half of the deliveries from S1P(2)(-/-) pregnant mice resulted in neonatal death. In situ hybridization revealed exclusive s1p(2) expression in the hippocampal pyramidal/granular neurons of wild-type mice, and immunohistochemistry/microarray analyses identified enhanced gliosis in the whole hippocampus and its neighboring neocortex in seizure-prone adult S1P(2)(-/-) mice. Seizure-prone adult S1P(2)(-/-) mice displayed impaired spatial working memory in the eight-arm radial maze test and increased anxiety in the elevated plus maze test, whereas their passive avoidance learning memory performance in the step-through test and hippocampal long-term potentiation was indistinguishable from that of wild-type mice. Our findings suggest that blockade of S1P(2) signaling may cause seizures/hippocampal insults and impair some specific central nervous system functions.
- Subjects :
- medicine.medical_specialty
Elevated plus maze
Video Recording
Hippocampus
In Vitro Techniques
Motor Activity
Hippocampal formation
Spatial memory
Mice
Behavioral Neuroscience
Epilepsy
Seizures
Internal medicine
Convulsion
Avoidance Learning
medicine
Animals
Gliosis
Maze Learning
Sphingosine-1-Phosphate Receptors
Oligonucleotide Array Sequence Analysis
Mice, Knockout
Neurons
Brain Mapping
Memory Disorders
Neocortex
business.industry
Gene Expression Profiling
Age Factors
Brain
Electroencephalography
Long-term potentiation
medicine.disease
Mice, Inbred C57BL
Receptors, Lysosphingolipid
Memory, Short-Term
medicine.anatomical_structure
Endocrinology
Animals, Newborn
Neurology
Space Perception
Neurology (clinical)
medicine.symptom
business
Neuroscience
Subjects
Details
- ISSN :
- 15255050
- Volume :
- 22
- Database :
- OpenAIRE
- Journal :
- Epilepsy & Behavior
- Accession number :
- edsair.doi.dedup.....35bf3a99f581aa4a1b5d294e4b8525da