Differential microglial inflammatory responses in the spinal cord and brain towards chronic neuropathic pain in rats

Differential microglial inflammatory responses in the spinal cord and brain towards chronic neuropathic pain in rats

S196 P.1.d. Basic and clinical neuroscience − Glia-neuron interaction squared test, Fisher’s test, ANOVA test, the Mann–Whitney U test, k-means clus...

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S196

P.1.d. Basic and clinical neuroscience − Glia-neuron interaction

squared test, Fisher’s test, ANOVA test, the Mann–Whitney U test, k-means clustering analysis, logistic regression. Results: Overweight was present in 20 boys (18.35%) and obesity in 4 (3.6%). Due to a small number of overweight boys the prevalence of overweight, understood as abnormally elevated body mass, was evaluated in all analyses. Statistically significantly less frequently present in the overweight group of patients were: T allele of rs1800955 DRD4 (p = 0.03), A allele of rs363039 SNAP25 (p = 0.04), C allele of rs363043 SNAP25 (p = 0.01) and C allele of rs17288723 5HTR2A (p = 0.04). CT and TT genotypes of polymorphism rs1800955, DRD4 gene (p = 0.03) were related to lower prevalence of overweight than CC, similarly to rs363039 SNAP25 GA and AA (p = 0.04) in comparison with GG. However, TT genotype of rs363043 SNAP25 was related to significantly increased risk of overweight in relation to TC and CC (p = 0.02). The analysis did not show any statistically significant differences in the levels of neuropsychological test results between the patients with and without overweight. Conclusions: Overweight in ADHD boys is related to a single nucleotide polymorphism of 3 candidate genes: rs1800955 DRD4, rs363039 i rs363043 SNAP25 and rs17288723 5HTR2A but not to deficiency determinants in selected executive functions. References [1] Han´c, T., Słopie´n, A., Wola´nczyk, T., Szwed A, Czapla, Z., Durda, M., & Ratajczak J., 2015. Attention-Deficit/ Hyperactive Disorder is related to decreased weight in preschool period and increased rate of overweight in school age boys. J Child Adolesc Psychopharmacol, 25, 691–700. ¨ P¨utter, C., Volckmar, A.L., Cichon, S., Hoffmann, P., [2] Albayrak, O., N¨othen, M, M., Hinney, A., 2013. Common Obesity Risk Alleles in Childhood Attention-Deficit/Hyperactivity Disorder. Am J Med Genet B Neuropsychiatr Genet, 162, 295–305. [3] Reinert, K.R.S., Po’e, E.K., & Barkin, S.L., 2013. The Relationship between Executive Function and Obesity in Children and Adolescents: A systematic Literature Review. J Obes, doi: 10.1155/2013/820956. [4] Willcutt, E.G., Doyle, A.E., Nigg, J.T., Faraone, S.V., & Pennington, B.F., 2005. Validity of the Executive Function Theory of AttentionDeficit/Hyperactivity Disorder: A Meta-Analytic Review. Biol Psychiatry, 57, 1336–1346.

P.1.d. Basic and clinical neuroscience − Glia-neuron interaction P.1.d.002 Differential microglial inflammatory responses in the spinal cord and brain towards chronic neuropathic pain in rats Li1 ° ,

Wei2 ,

Piirainen1 ,

Chen2 ,

Kalso3 ,

Z. Z. E. H. S. A. Pertovaara2 , L. Tian1 1 University of Helsinki, Neuroscience Center, Helsinki, Finland; 2 University of Helsinki, Department of Physiology- Faculty of Medicine, Helsinki, Finland; 3 University of Helsinki, Department of Pharmacology- Faculty of Medicine, Helsinki, Finland Introduction: Neuropathic pain is a complex pain state caused by dysfunction of somatosensory nervous system. Most cases of neuropathic pain are chronic and patients often develop comorbidities such as anxiety, depression and sleep disturbance. Currently available pain-relievers are not universally effective and often lack long-lasting efficacy due to the development of analgesic tolerance. To understand the cellular and molecular mechanisms underlying the initiation and development of neuropathic pain, several experimental rodent models, such as spared nerve injury

(SNI), have been used. With these models, glia cells, such as microglia, have been appreciated in neuropathic pain following peripheral nerve injury. However, the exact roles that microglia play remain unclear. Aims of study: Our aim is to understand the temporal and spatial roles that microglia play at different stages in the course of neuropathic pain. Methods: To verify development of neuropathic pain-like mechanical hypersensitivity in SNI rats, we assessed the hind paw withdrawal response towards von Frey hair stimulation. Since anxiety is one of the comorbidities developed during neuropathic pain, we thus performed a light-dark test to evaluate the anxietylike behavior of SNI rats. To understand the role of microglia in neuropathic pain, we simultaneously measured microgliosis and characterized microglial activation profiles in the ipsilateral lumbar spinal cord (SC) and contralateral prefrontal cortex (PFC) of SNI rats at different stages following SNI surgery by an efficient and reproducible multicolor flow cytometry. Moreover, we compared differential gene expression in the ipsilateral lumbar dorsal horn of SNI rats by transcriptomic analysis using public available datasets. Finally, we examined whether chronic systemic minocycline treatment has effects on spinal microglial activation and mechanical allodynia in SNI rats. Data in this study were analyzed by two-way ANOVA with Bonferroni’s post hoc or Student’s t test. Summary: In consistency with our immunohistochemistry data, we observed increased microgliosis in the ipsilateral but not contralateral lumbar SC of SNI rats as compared to Sham controls on both post-operative day (POD)7 and 21. As regard to microglial activation, we unexpectedly found an anti-inflammatory microglial response in the ipsilateral lumbar SC but an opposite response in the contralateral PFC of SNI rats as compared to Sham controls on POD21. A further DNA microarray analysis in the ipsilateral lumbar dorsal horns of SNI rats revealed that the most significantly differentially expressed genes were involved in immune and microglial activation. Daily systemic minocycline treatment lasting for two weeks attenuated spinal microglial activation on POD21, but failed to alleviate existing neuropathic pain-like mechanical allodynia. Conclusion: Taken together, our results suggest that microglia in the SC and brain are differentially activated in response to peripheral nerve injury, and that spinal microglia do not necessarily develop into a pro-inflammatory subtype as many literatures suggested, at least not in the SNI model. P.1.d.004 Sex-difference in rapid changes of hippocampal astrocytes and serum level of BDNF one hour after ketamine treatment M. Ardalan1,2 ° , B. Elfving1 , R.N. Jens2,3 , A. Mathe4 , G. Wegener1,5 1 Translational Neuropsychiatry Unit, Department of Clinical Medicine- Aarhus University Hospital, Risskov, Denmark; 2 Stereology and Electron Microscopy Laboratory, Department of Clinical Medicine- Aarhus University Hospital, Aarhus, Denmark; 3 Center for Stochastic Geometry and Advanced Bioimaging, Aarhus University, Aarhus, Denmark; 4 Karolinska Institutet, Department of Clinical Neuroscience - Karolinska Universitetssjukhuset, Stockholm, Sweden; 5 Pharmaceutical Research Center of Excellence, School of Pharmacy- North-West University, Potchefstroom, South Africa Background: The prevalence of major depression among women is higher than men. Preclinical studies indicate that astrocytes