Dataset Information

SAR110894, a potent histamine H3-receptor antagonist, displays disease-modifying activity in a transgenic mouse model of tauopathy.

ABSTRACT: INTRODUCTION:Tau hyperphosphorylation and neurofibrillary tangles are histopathologic hallmarks of tauopathies. Histamine H3-receptor antagonists have been proposed to reduce tau hyperphosphorylation in preclinical models. METHODS:We evaluated the ability of SAR110894, a selective histamine H3-receptor antagonist, to inhibit tau pathology and prevent cognitive deficits in a tau transgenic mouse model (THY-Tau22). RESULTS:SAR110894 treatment for 6 months (but not 2 weeks) in THY-Tau22 mice decreased both tau hyperphosphorylation at pSer396-pSer404 (AD2 signal) in the hippocampus and the number of AT8 (pSer199/202-Thr205) positive cells in the cortex and decreased the formation of neurofibrillary tangles in the cortex, hippocampus, and amygdala. Macrophage inflammatory protein 1-alpha messenger RNA expression was decreased in the hippocampus. SAR110894 also prevented episodic memory deficits, and this effect was still detected after treatment washout. DISCUSSION:Long-term SAR110894 treatment could have potential disease modifying activity in neurodegenerative tauopathies.

SUBMITTER: Delay-Goyet P

PROVIDER: S-EPMC5651361 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

SAR110894, a potent histamine H3-receptor antagonist, displays disease-modifying activity in a transgenic mouse model of tauopathy.

Delay-Goyet Philippe P Blanchard Véronique V Schussler Nathalie N Lopez-Grancha Mati M Ménager Jean J Mary Véronique V Sultan Eric E Buzy Armelle A Guillemot Jean-Claude JC Stemmelin Jeanne J Bertrand Philippe P Rooney Thomas T Pradier Laurent L Barnéoud Pascal P

Alzheimer's & dementia (New York, N. Y.) 20161103 4

<h4>Introduction</h4>Tau hyperphosphorylation and neurofibrillary tangles are histopathologic hallmarks of tauopathies. Histamine H3-receptor antagonists have been proposed to reduce tau hyperphosphorylation in preclinical models.<h4>Methods</h4>We evaluated the ability of SAR110894, a selective histamine H3-receptor antagonist, to inhibit tau pathology and prevent cognitive deficits in a tau transgenic mouse model (THY-Tau22).<h4>Results</h4>SAR110894 treatment for 6 months (but not 2 weeks) in ...[more]

PMID: 29067314

Similar Datasets

Project description:Hemorrhagic shock has a potential to be life-threatening when it is not treated. The main causes of hemorrhagic shock involve: (1) forces causing injury; and (2) diseases that can cause hemorrhage., Therefore, due to the causes of hemorrhagic shock and the life-threatening potential, the search for new methods of shock treatment is extremely valuable to the modern medicine. The aim of this study was to investigate the influence of clobenpropit in the model of hemorrhagic shock. The experiments were conducted in 110 adult male Wistar rats weighing between 205 and 470g. 1, 2 and 5 ?mol/kg of intravenous H3 receptors reverse agonists, clobentropit, and/or 1, 5 and 10 ?mol/kg H3 receptor agonist, imetit, were used as general anesthetics. Irreversible hemorrhagic shock was induced by the paused bleeding until the mean arterial pressure (MAP) lowered to the level of 20-25 mmHg. It was proved that, in cases of critical hypotension, clobenpropit triggered a dose-dependent increase of: systolic blood pressure (SBP), diastolic blood pressure (DBP), MPA and heart rate (HR) of rats with critical hypotension. The most significant changes in hemodynamic parameters were achieved by administrating dosages of 2 mmol/kg. This resulted in the survival rate increase to up to 100%. However, imetit did not trigger any hemodynamic changes nor an increase in SBP, DBP, MAP or HR. Furthermore, it was found that the premedication with prazosin, yohimbine, 6-hydroxydopamine and the vasopressin V1a receptor antagonist blocked the effects of clobenpropit. Additionally, premedication with propranolol, captopril and ZD 7155 did not cause any significant changes in the measured hemodynamic parameters. In conclusion, after an intravenous injection clobenpropit, the inverse agonist of H3 histamine receptors/agonist of histamine receptors H4, causes a resuscitating effect on rats in hemorrhagic shock. Moreover, such effect is based on the effector mechanisms of sympathetic nervous system and vasopressin.

Dataset Information

SAR110894, a potent histamine H3-receptor antagonist, displays disease-modifying activity in a transgenic mouse model of tauopathy.

Publications

SAR110894, a potent histamine H3-receptor antagonist, displays disease-modifying activity in a transgenic mouse model of tauopathy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets