Abstract
Cognitive impairments affect millions of people worldwide with an increasing
prevalence. Research on their etiology and treatment is developing, nevertheless
significant gaps remain. Trientine (TETA), as a copper chelator, has been shown
to have beneficial effects in different human chronic diseases such as diabetic
cardiomyopathy and neuropathy. Here, we examined the impact of TETA on
AlCl3-induced neurocognitive dysfunctions and molecular changes
in the hippocampus of rats.
Thirty-six male Wistar rats (weighing 200–250 g) were randomly divided into four
groups including control, TETA (100 mg/kg/day), AlCl3
(100 mg/kg/day), and AlCl3 (100 mg/kg/day)+TETA (100 mg/kg/day), and
received chemicals by gavage for 30 days. At the end of the treatment, the open
field maze, elevated plus maze, novel object recognition memory test, and
shuttle box test were done. Then after, brain-derived neurotrophic factor
(BDNF), glycogen synthase kinase-3 β (GSK-3β), acetylcholinesterase activity,
oxidative stress markers, and inflammatory mediators were measured in the
hippocampus.
AlCl3 increased anxiety-like behaviors and impaired recognition and
short-term memory. TETA was able to improve AlCl3-induced
anxiety-like behaviors and short-term memory dysfunction. In the
AlCl3-treated group, there was a significant increase in GSK-3β,
oxidative stress, pro-inflammatory and pro-apoptotic markers, and decreased BDNF
in the hippocampus. Co-administration of TETA was able to decrease lipid
peroxidation, inflammation, GSK-3β, and acetylcholinesterase activity, and
increase BDNF in the hippocampus compared with AlCl3-treated
rats.
It can be concluded that TETA was able to improve neurobehavioral and
neurocognitive functions by alleviating oxidative stress, inflammation, and
pro-apoptotic pathways leading to the normalization of BDNF and GSK-3β.
Keywords
aluminum - Alzheimer - cognitive - inflammation - oxidative stress - triethylenetetramine
