Pharmacological Effects of Turmeric on Learning, Memory and Expression of Muscarinic Receptor Genes (M1, M3 and M5) in Stress-induced Mouse Model

Chunghyul-Dan (CHD) is the first choice agent for the prevention and treatment of stroke at the Kyung Hee Medical Hospital. To date, CHD has been reported to have beneficial effects on brain disease in animals and humans, along with antioxidative and anti-inflammatory effects. The aim of this study was to evaluate the pharmacological effects of CHD on a traumatic brain injury (TBI) mouse model to explore the possibility of CHD use in patients with TBI. The TBI mouse model was induced using the controlled cortical impact method. CHD was orally administered twice a day for 5 d after TBI induction; mice were assessed for brain damage, brain edema, blood-brain barrier (BBB) damage, motor deficits, and cognitive impairment. Treatment with CHD reduced brain damage seen on histological examination and improved motor and cognitive functions. However, CHD did not reduce brain edema and BBB damage. In conclusion, CHD could be a candidate agent in the treatment of patients with TBI. Further studies are needed to assess the exact mechanisms of the effects during the acute-subacute phase and pharmacological activity during the chronic-convalescent phase of TBI.

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Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model

Neuropsychopharmacology ◽

10.1038/npp.2015.189 ◽

2015 ◽

Vol 41 (2) ◽

pp. 598-610 ◽

Cited By ~ 45

Author(s):

A Ghoshal ◽

J M Rook ◽

J W Dickerson ◽

G N Roop ◽

R D Morrison ◽

...

Keyword(s):

Mouse Model ◽

Muscarinic Receptor ◽

Cognitive Symptoms ◽

M1 Muscarinic

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Pharmacological effects of methoctramine on muscarinic receptor subtypes mediating vasodilatation

Pharmacological Research Communications ◽

10.1016/s0031-6989(88)80516-2 ◽

1988 ◽

Vol 20 ◽

pp. 386

Author(s):

M.C. Tonnini ◽

M.L. Cingolani ◽

P. Pigini ◽

M.T. Picchio ◽

P. Angeli ◽

...

Keyword(s):

Muscarinic Receptor ◽

Receptor Subtypes ◽

Pharmacological Effects ◽

Muscarinic Receptor Subtypes

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BLOCKADE OF M4 MUSCARINIC RECEPTORS ON STRIATAL CHOLINERGIC INTERNEURONS NORMALIZES STRIATAL DOPAMINE RELEASE IN A MOUSE MODEL OF DYT1-TOR1A DYSTONIA

10.1101/2020.12.17.423273 ◽

2020 ◽

Author(s):

Anthony M. Downs ◽

Yuping Donsante ◽

H.A. Jinnah ◽

Ellen J. Hess

Keyword(s):

Mouse Model ◽

Muscarinic Receptor ◽

Mechanism Of Action ◽

Striatal Dopamine ◽

Receptor Subtype ◽

Cholinergic Interneurons ◽

Striatal Dopamine Release ◽

M4 Muscarinic Receptor ◽

Subtype Selective ◽

Da Release

ABSTRACTTrihexyphenidyl (THP), a non-selective muscarinic receptor (mAChR) antagonist, is the preferred oral pharmaceutical for the treatment of DYT1-TOR1A dystonia. A better understanding of the mechanism of action of THP is a critical step in the development of better therapeutics with fewer side effects. Using a mouse model of DYT1-TOR1A dystonia (Tor1a+/ΔE KI mice), we recently found that THP normalized striatal DA release, revealing a plausible mechanism of action for this compound. However, the exact mAChR subtypes that mediate this effect remain unclear. In this study we used a combination of a newly developed M4 subtype-selective mAChR antagonist and cell-type specific mAChR KO mice to determine which mAChR subtypes mediate the DA enhancing effects of THP. We determined that THP and the M4 subtype-selective mAChR antagonist enhance striatal DA release by blocking M4 mAChR on striatal cholinergic interneurons in Tor1a+/ΔE KI mice. However, in Tor1a+/+ mice THP increases striatal DA release through a combination of M1 and M4 mAChR, which reveals an alteration in M1 mAChR function in Tor1a+/ΔE KI mice. Taken together these data implicate a principal role for M4 mAChR located on striatal cholinergic interneurons in the mechanism of action of THP and suggest that M4-subtype selective mAChR antagonists may be more efficacious therapeutics for DYT1-TOR1A dystonia.SIGNIFICANCE STATEMENTTrihexyphenidyl, a non-selective muscarinic receptor antagonist, is the preferred oral therapeutic for DYT1-TOR1A dystonia, but it is poorly tolerated due to significant side effects. A better understanding of the mechanism of action of trihexyphenidyl is needed for the development of improved therapeutics. We recently found that trihexyphenidyl rescues the deficit in both striatal dopamine release and steady-state extracellular striatal dopamine concentrations in a mouse model of DYT1-TOR1A dystonia. However, the precise muscarinic receptor subtype(s) that mediate these effects are unknown. We used a newly developed M4 muscarinic receptor subtype-selective antagonist along with M1 and M4 muscarinic receptor knockout mice to determine the precise muscarinic receptor subtypes that mediate the dopamine-enhancing effects of trihexyphenidyl.

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Immunotropic aspect of the Bacillus coagulans probiotic action

10.1101/088757 ◽

2016 ◽

Author(s):

T.V. Bomko ◽

T. N. Nosalskaya ◽

T. V. Kabluchko ◽

Yu. V. Lisnyak ◽

A. V. Martynov

Keyword(s):

Weight Loss ◽

Mouse Model ◽

Preventive Measures ◽

Reference Product ◽

Bacillus Coagulans ◽

Pharmacological Effects ◽

Intestinal Dysbiosis ◽

Cellular Immunodeficiency ◽

Pharmacological Method

AbstractImmunotropic aspect of the Bacillus coagulans probiotic actionObjectiveCurrently, probiotics are increasingly used as the alternative to antibiotics as well as the preventive measures in humans. In particular, probiotics occupy a key position in the treatment of antibiotics-associated intestinal dysbiosis. A spore-forming microorganism lactobacillus Bacillus coagulans is one of the most promising probiotics. However, some of its pharmacological effects remain poorly understood.Aim.This study is aimed at investigation of the effect of Bacillus coagulans (Laktovit Forte) on the intestinal dysbiosis syndrome in mice caused by streptomycin against the background of cyclophosphamide-induced cellular immunodeficiency.Methods.Pharmacological method: mouse model in vivo with immunodeficiency caused by cyclophosphamide.Key findings.In mice with colitis caused by streptomycin treatment, the administration of Bacillus coagulans (Laktovit Forte medicinal product) resulted in an antidiarrheal effect, normalization of gastrointestinal motility, and prevention of the animals’ weight loss. Given the cyclophosphamide-induced immunosuppression and streptomycin-associated diarrhoea, the immunity was completely restored only under the action of Bacillus coagulans.Conclusions.According to all parameters, Bacillus coagulans has been proved to be more effective as compared to the Linex Forte reference product containing lacto‐ and bifidobacteria.

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