β-Asarone Rescues Pb-Induced Impairments of Spatial Memory and Synaptogenesis in Rats

Abstract

Chronic lead (Pb) exposure causes cognitive deficits. This study aimed to explore the neuroprotective effect and mechanism of β-asarone, an active component from Chinese Herbs Acorus tatarinowii Schott, to alleviate impairments of spatial memory and synaptogenesis in Pb-exposed rats. Both Sprague-Dawley developmental rat pups and adult rats were used in the study. Developmental rat pups were exposed to Pb throughout the lactation period and β-asarone (10, 40mg kg-1, respectively) was given intraperitoneally from postnatal day 14 to 21. Also, the adult rats were exposed to Pb from embryo stage to 11 weeks old and β-asarone (2.5, 10, 40mg kg-1, respectively) was given from 9 to 11 weeks old. The level of β-asarone in brain tissue was measured by High Performance Liquid Chromatography. The Morris water maze test and Golgi-Cox staining method were used to assess spatial memory ability and synaptogenesis. The protein expression of NR2B subunit of NMDA receptor, Activity-regulated cytoskeleton-associated protein (Arc/Arg3.1) and Wnt family member 7A (Wnt7a) in hippocampus, as well as mRNA expression of Arc/Arg3.1 and Wnt7a, was also explored. We found that β-asarone could pass through the blood brain barrier quickly. And β-asarone effectively attenuated Pb-induced reduction of spine density in hippocampal CA1 and dentate gyrus areas in a dose-dependent manner both in developmental and adult rats, meanwhile the Pb-induced impairments of learning and memory were partially rescued. In addition, β-asarone effectively up-regulated the protein expression of NR2B, Arc and Wnt7a, as well as the mRNA levels of Arc/Arg3.1 and Wnt7a, which had been suppressed by Pb exposure. The results suggest the neuroprotective properties of β-asarone against Pb-induced memory impairments, and the effect is possibly through the regulation of synaptogenesis, which is mediated via Arc/Arg3.1 and Wnt pathway.

Extracts or Active Components from Acorus gramineus Aiton for Cognitive Function Impairment: Preclinical Evidence and Possible Mechanisms

“…After reading the remaining 285 full-text articles, 228 studies were excluded for at least one of following reasons: (1) not an animal study; (2) the article was not a research about cognitive impairment; (3) the study did not access the effects of AGA or active component on the animal model of cognitive impairment; (4) EAAGA was not used as a monotherapy; and (5) lack of control group. Ultimately, 34 eligible articles [ 5 , 6 , 10 , 11 , 17 – 46 ] were selected ( Figure 1 ) .…”

“…The weight of SD rats ranged from 200 g to 650 g, the weight of Wistar rats used ranged from 30 g to 250 g, and the weight of mice ranged from 17 g to 50 g. Twenty-two studies used male rodents, 1 study used female rodents, 5 study used both female and male rodents, and the remaining 6 studies did not provide gender details. Sodium pentobarbital was used to induce anesthesia in 8 studies, and chloral hydrate was used in 2 studies [ 20 , 21 ], 1 study [ 41 ] used phenytoin sodium, 1 study [ 17 ] used CO 2 , and 1 study [ 10 ] used isoflurane, while the remaining 21 studies did not report the type of anesthetics. Cognitive impairment models were induced by lead [ 17 ], noise stress [ 18 ], LPS [ 19 ], amyloid beta 1-42 [ 11 , 21 , 26 , 28 , 29 , 37 , 41 , 46 ], D-gal plus AlCl 3 [ 22 ], scopolamine [ 5 , 24 , 30 , 34 – 36 , 42 , 45 ], ethanol [ 5 , 32 , 34 – 36 ], sodium nitrite [ 5 , 32 ], corticosterone [ 23 ], Ibotenic acid [ 25 ], chronic restraint stress [ 31 ], pentobarbital sodium [ 32 ], D-galactose [ 33 , 38 ], AlCl 3 [ 40 ] , streptozotocin (STZ) [ 43 ], pent ylenetet razol (PTZ) [ 44 ], and NaNO 2 [ 34 – 36 ].…”

A Hypothesis of the Interaction of the Nitrergic and Serotonergic Systems in Aggressive Behavior Induced by Exposure to Lead

“…β-asarone is an active oriental herb component which reverts damage inflicted by Pb over spatial memory, possibly through synaptogenesis (Yang et al, 2016 ). Developmental rat pups were exposed to Pb throughout lactation period and β-asarone (10, 40 mg/kg, respectively) was administered intraperitoneally from postnatal day 14–21.…”

“…The above mentioned results suggest neuroprotective properties of β-asarone against Pb-induced memory impairments and an effect possibly related to the regulation of synaptogenesis, mediated via Arc/Arg3.1 and Wnt pathway. Traditional use and clinical reports showed that β-asarone is effective for the treatment of learning and memory deficits; therefore, it is likely to manage memory impairment following chronic Pb exposure (Yang et al, 2016 ).…”

The Neurotrophic and Anti-Inflammatory Effect of β-asarone on the DA-Induced the Pathology of Minimal Hepatic Encephalopathy

“…Moreover, β-asarone increased the expression of neurotrophin such as brain-derived neurotrophic factor (BDNF), glial cellderived neurotrophic factor, and ciliary neurotrophic factor in RSC96 cells [19]. β-asarone treatment also improved the spatial learning and memory in Aβ (1-42)-induced memory-impaired rats [20]; in transgenic model of Alzheimer's disease such as Senescence-accelerated prone-8 (SAMP-8) mice [21]; and AβPP/PS1 double transgenic mice [22,23],also in chronic exogenous corticosterone-induced memoryimpaired rats [24,25]. Then, we describe that the attribution of pathogenesis of MHE is upregulation of DA, followed by the production of TNFα from neurons, leading to the disruption of synaptic formation, which was diminished by βASA treatment.…”