Current advances of pharmacological properties of 7-chloro-4-(phenylselanyl) quinoline: Prevention of cognitive deficit and anxiety in Alzheimer’s disease model


BIBLIOGRAPHIC THERAPEUTIC AGENT ANIMAL MODEL EXPERIMENTAL DESIGN OUTCOMES

Bibliographic

Year of Publication:
2018
Contact PI Name:
Cristiane Luchese
Contact PI Affiliation:
Programa de Pós-graduação em Bioquímica e Bioprospecção, CCQFA, UFPel, Campus Capão do Leão, Pelotas, Brazil
Co-Authors:
Mikaela P. Pinz, Angélica S. dos Reis, Ane G. Vogt, Roberta Krüger, Diego Alves, Cristiano R. Jesse, Silvane S. Roman, Mauro P. Soares, Ethel A. Wilhelm
Primary Reference (PubMED ID):
Funding Source:
Brazilian National Council for Scientific and Technological Development (CNPq)
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS)
Study Goal and Principal Findings:

This study investigated the effect of 7-chloro-4-(phenylselanyl) quinoline (4-PSQ) at a dose of 1 mg/kg in memory impairment and anxiety in an Alzheimer’s disease (AD) model induced by amyloid β-peptide (Aβ) (fragment 25–35) in mice. The involvement of acetylcholinesterase (AChE) activity and lipid peroxidation in hippocampus and cerebral cortex was evaluated. Male Swiss mice were pretreated with 4-PSQ (1 mg/kg, intragastrically (i.g.), daily) for fourteen days. Thirty minutes after the first treatment with 4-PSQ, the animals received a single injection of Aβ (3 nmol/3 μl/per site, intracerebroventricular (i.c.v.)). Mice were submitted to the behavioral tasks (open-field, elevated plus maze, Barnes maze, object recognition and location, and stepdown inhibitory avoidance tests) from the fifth day onwards. On the fifteenth day, blood was removed for analysis of biochemical markers (glucose, triglycerides, urea, aspartate (AST) and alanine (ALT) aminotrasferases), and cerebral cortex and hippocampus for determination of AChE activity and thiobarbituric acid reactive species (TBARS) levels. Aβ caused memory impairment, anxiogenic behavior, increased AChE activity in the cerebral structures and TBARS levels in the cerebral cortex. 4-PSQ was effective to protect against behavioral changes, AChE activity and TBARS levels. In conclusion, 4-PSQ protected against learning and memory impairment and anxiety in a mouse model of AD induced by Aβ, and anticholinesterase and antioxidant actions are involved in the pharmacological effect of the compound.

Bibliographic Notes:
Ethel A. Wilhelm and Cristiane Luchese (Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas (UFPel), Pelotas, RS, Brazil) are corresponding authors on this paper.

Therapeutic Agent

Therapeutic Information:
Therapy Type:
Small Molecule
Therapeutic Agent:
4-PSQ (7-chloro-4-phenylselenyl quinoline)
Therapeutic Target:
Multi Target

Animal Model

Model Information:
Species:
Mouse
Model Type:
beta Amyloid Peptide Injection
Strain/Genetic Background:
Swiss

Experimental Design

Is the following information reported in the study?:
Power/Sample Size Calculation
Randomized into Groups
Blinded for Treatment
Blinded for Outcome Measures
Pharmacokinetic Measures
Pharmacodynamic Measures
Toxicology Measures
ADME Measures
Biomarkers
Dose
Formulation
Route of Delivery
Duration of Treatment
Frequency of Administration
Age of Animal at the Beginning of Treatment
Age of Animal at the End of Treatment
Sex as a Biological Variable
Study Balanced for Sex as a Biological Variable
Number of Premature Deaths
Number of Excluded Animals
Statistical Plan
Genetic Background
Inclusion/Exclusion Criteria Included
Conflict of Interest

Outcomes

Outcome Measured
Outcome Parameters
Behavioral
Barnes Maze
Elevated Plus Maze
Exploratory Activity
Inhibitory Avoidance Test
Novel Object Recognition Test (NORT)
Object Place Recognition
Open Field Test
Motor Function
Locomotor Activity
Biochemical
Acetylcholinesterase (AChE) Activity
Malondialdehyde (MDA)
Toxicology
Alanine Aminotransferase (ALT)
Aspartate Aminotransferase (AST)
Glucose Concentration
Triglycerides
Urea
Outcomes Notes:
Plasma levels of glucose, triglycerides and urea, and ALT and AST activity were measured to rule out any toxic effect of 4-PSQ.

Source URL: http://alzped.nia.nih.gov/current-advances