Abstract
Tianeptine is an atypical antidepressant drug with proven efficacy, but still not fully understood mechanism of action. Recently it has been suggested that tianeptine may modulate inflammatory processes, however there is a lack of data on its influence on microglia - the main source of pro-inflammatory cytokines in the brain. Therefore this project aimed to investigate whether tianeptine can influence activation of microglial cells. We conducted our study in two experimental models: in vivo – in the hippocampus and frontal cortex of adult rats and in vitro in microglial cultures. Pregnant rats were subjected daily to 3 stress sessions from 14th day of pregnancy until delivery. Control pregnant females were left undisturbed in their homecages. Microglial cells were pre-treated for 30min with different concentrations of tianeptine and stimulated with LPS (100ng/ml). Next, expression of microglial activation markers and pro-inflammatory cytokines were evaluated. In the second part of experiments at 3 months of age, after behavioral verification, control and prenatally stressed rats were injected with tianeptine (10mg/kg i.p.) for 14 days. Next, biochemical studies were carried out on hippocampus and frontal cortex. We observed that in microglial pre-treatment with tianeptine (1-10uM) reduced the expression of microglial activation markers (CD40 and MHCII) and production of pro-inflammatory cytokines. Moreover, in adult animals subjected to prenatal stress (an animal model of depression) chronic tianeptine treatment inhibited microglial activation (decreased CD40 and CD68 expression) in both examined structures. In conclusion, our results show that tianeptine exerts anti-inflammatory properties suppressing microglial activation in both in vitro and in vivo experimental models.
Highlights
Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia
The results of the present study indicate that development of the neuronal hypoxic tolerance induced by the three-trial, in contrast to one-trial, mild hypoxic preconditioning is apparently largely associated with the activation of CREB, as well as brain-derived neurotrophic factor (BDNF) and Bcl-2 overexpression
No significant differences in serum level of Solubile form of RAGE (sRAGE) where found between rapidly progressing and slow progressing subgroup of multiple sclerosis (MS) patients.Our results suggest for the role of sRAGE in MS ethiopathogenesis, but we did not find any association of sRAGE in serum with the rate of MS disability progression
Summary
Alzheimer’s disease (AD) is an incurable neurodegenerative disease characterized by progressive dementia. The aim of the study was to characterize the effects of streptozocin (STZ)-indced diabetes on learning and memory of 5XFAD and wild-type (WT) mice in Morris water maze (MWM) at ages 2 and 6 months and on brain amyloid load. Existing evidence suggests GABAergic system is involved in pathophysiology of Alzheimer’s disease (AD) via inhibitory interneuron deficits (Verret et al, 2012) and decrease in functional GABAA receptors (Limon et al, 2012). Our concept: low doses of muscimol may prevent learning/memory deficits in intracerebroventricular (icv) streptozocin (STZ)-induced AD nontransgenic rat model. The Sigma-1 receptor is a chaperone protein that modulates intracellular calcium signalling of the endoplasmatic reticulum and is involved in learning and memory processes.The aim of the present study was to compare in vitro Ca2+ concentration modulating activity and in vivo behavioural effects of enantiomers of methylphenylpiracetam, a novel positive allosteric modulator of Sigma-1 receptors
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