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Behav Brain Res. 2018 Jan 30;337:99-106. doi: 10.1016/j.bbr.2017.10.002. Epub 2017 Oct 3.

The effects of betulinic acid on neurobehavioral activity, electrophysiology and histological changes in an animal model of the Alzheimer's disease.

Author information

1
Department of Physiology, Faculty of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
2
Cellular & Molecular Research Center, Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
3
Cellular & Molecular Research Center, Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; Department of Immunology, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
4
Department of Physiology, Faculty of Medicine, Physiology Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Electronic address: Farbood_y@yahoo.com.

Abstract

Alzheimer's disease (AD) is a common disorder characterized by aggregation and conversion of amyloid beta (Aβ) monomers to fibrils. Betulinic acid (BA) strongly accelerated this pathway through circumventing the oligomeric intermediate state. BA at doses of 0.2 and 0.4μM/10μl/rat (intra-hippocampal or i.h injection, vehicle: DMSO) was bilaterally administrated 180 and 10min before co-administration of Aβ (0.1μM/5μl/rat, i.h injection, vehicle: PBS) and Streptozotocin (STZ, 1.5mg/kg/10μl/rat, intracerebroventricular or i.c.v. injection, vehicle: aCSF). The behavioral assessments (spatial and passive avoidance memory, anxiety, locomotion, depression, and motor coordination), electrophysiological evaluations (hippocampal long- term potentiation (LTP)) as well as histological changes were evaluated 30days after injections. The indices of spatial and passive avoidance memory, anxiety/depression and LTP records were significantly impaired in AD rats in comparison with the sham. Pretreatment of BA (0.4μM) showed a more significant effect on memory, anxiety, all LTP parameters, and histological damage compared to a low dose in contrast to the AD group. Overall, BA pretreatment was able to prevent AD-induced neurobehavioral and LTP deficits in rats and the best effect was observed in molar ratio of 1:4 (Aβ to BA).

KEYWORDS:

Alzheimer’s disease; Anxiety/depression; Betulinic acid; LTP; Memory; Rat

PMID:
28986104
DOI:
10.1016/j.bbr.2017.10.002
[Indexed for MEDLINE]

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