Effects of Aged Garlic Extract on Cholinergic, Glutamatergic and GABAergic Systems with Regard to Cognitive Impairment in Aβ-Induced Rats

Abstract

Alzheimer’s disease (AD) has been linked to the degeneration of central cholinergic and glutamatergic transmission, which correlates with progressive memory loss and the accumulation of amyloid-β (Aβ). It has been claimed that aged garlic extract (AGE) has a beneficial effect in preventing neurodegeneration in AD. Therefore, the objective of this study was to investigate the effects of AGE on Aβ-induced cognitive dysfunction with a biochemical basis in the cholinergic, glutamatergic, and GABAergic systems in rats. Adult male Wistar rats were orally administered three doses of AGE (125, 250, and 500 mg/kg) daily for 65 days. At day 56, they were injected with 1 μL of aggregated Aβ (1–42) into each lateral ventricle, bilaterally. After six days of Aβ injection, the rats’ working and reference memory was tested using a radial arm maze. The rats were then euthanized to investigate any changes to the cholinergic neurons, vesicular glutamate transporter 1 and 2 proteins (VGLUT1 and VGLUT2), and glutamate decarboxylase (GAD) in the hippocampus. The results showed that AGE significantly improved the working memory and tended to improve the reference memory in cognitively-impaired rats. In addition, AGE significantly ameliorated the loss of cholinergic neurons and increased the VGLUT1 and GAD levels in the hippocampus of rat brains with Aβ-induced toxicity. In contrast, the VGLUT2 protein levels did not change in any of the treated groups. We concluded that AGE was able to attenuate the impairment of working memory via the modification of cholinergic neurons, VGLUT1, and GAD in the hippocampus of Aβ-induced rats.

The antioxidant, aged garlic extract, exerts cytotoxic effects on wild-type and multidrug-resistant human cancer cells by altering mitochondrial permeability

“…AGE possesses greater antioxidant activity than fresh garlic by scavenging reactive oxygen species (ROS), enhancing the activity of cellular antioxidant enzymes (e.g., superoxide dismutase, catalase and glutathione peroxidase), mainly observed following the administration of SAC in vivo (16), and increasing glutathione levels in cells (17)(18)(19). Several studies on both animals and humans have shown that AGE contributes to a reduced risk of cancer (20,21), cardiovascular disease (22)(23)(24), Alzheimer's disease and other age-related degenerative conditions (19,25). Moreover, the mode of action of AGE in inhibiting the formation of atherosclerosis in apolipoprotein E-knockout mice has been investigated by examining whether AGE suppresses inflammation (26).…”

Ameliorative Effects of Dendropanax morbifera on Cognitive Impairment Via Enhancing Cholinergic Functions and Brain-Derived Neurotrophic Factor Expression in β-Amyloid-Induced Mice

“…Ab peptide has injurious effects, such as cholinergic dysfunction and impaired memory abilities, in mice. 27 Also, the downregulation of BDNF levels and unusual CREB signals were exhibited by AD patients and AD mouse model. 9,10 Previous studies have reported that various phytochemicals and plant extracts could prevent neuronal cell death and promote the recovery of cognitive function and neurotrophic factor after Ab peptide challenge.…”

“…Several reports have identified the role of ROS production in Ab-induced neurotoxicity, and discussed how various phytochemicals or plant extracts suppressed Abinduced neurotoxicity. 27 To further investigate the effects of DLE on the enhancement of cognitive functions, an ICV injection of Ab 1-42 into the mouse brain served as an in vivo model of AD. An ICV injection of Ab 1-42 led to cognitive dysfunction.…”

Benefits of aged garlic extract on Alzheimer's disease: Possible mechanisms of action (Review)

“…The neurotoxicity of Aβ has been reported to involve a number of neuronal events, such as the deficiency of neurotransmitters, and a decrease in vesicular transporters and synaptic transmissions, leading to neuronal cell death (41)(42)(43)(44). In addition, the effects of AGE on cholinergic, glutamatergic and GABAergic systems have been shown in rats with Aβ-induced cognitive impairment (45). AGE can significantly improve the working memory, as well as the reference memory of rats with Aβ-induced cognitive impairment in association with the amelioration of the loss of cholinergic neurons.…”