Protective effects of MK-801 on methylmercury-induced neuronal injury in rat cerebral cortex: Involvement of oxidative stress and glutamate metabolism dysfunction

The effects of the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 and the dihydropyridine calcium antagonist nimodipine on NMDA-induced phenomena were investigated using an in vivo fluorometric technique with indo-1. Indo-1, a fluorescent cytosolic free calcium ([Ca2+]i) indicator, was loaded into the cat cortex approximately 500 μm in depth by super-fusion with the membrane-permeant indo-1 acetoxymethyl ester (indo-1-AM). Changes in [Ca2+]i signals (400 and 506 nm) and reduced nicotinamide adenine dinucleotide (NADH) fluorescence (464 nm) were simultaneously measured directly from the cortex during ultraviolet excitation (340 nm). Superfusion of 100 μM NMDA over the exposed cortex induced an elevation of the [Ca2+]i signal ratio (400/506 nm), biphasic changes in NAD/NADH redox state (initial oxidation followed by progressive reduction), and characteristic changes in the EEG (abrupt depression in amplitude followed by an excitatory pattern of 18–22 Hz poly spikes or sharp waves). These changes were completely blocked by treatment with MK-801 and reduced by nimodipine. The mechanism underlying the protective effects of systemically administered MK-801 on the NMDA-induced neuronal injury was verified in vivo.

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High dietary fat induces NADPH oxidase-associated oxidative stress and inflammation in rat cerebral cortex

Experimental Neurology ◽

10.1016/j.expneurol.2004.10.011 ◽

2005 ◽

Vol 191 (2) ◽

pp. 318-325 ◽

Cited By ~ 191

Author(s):

X ZHANG ◽

F DONG ◽

J REN ◽

M DRISCOLL ◽

B CULVER

Keyword(s):

Oxidative Stress ◽

Cerebral Cortex ◽

Nadph Oxidase ◽

Dietary Fat ◽

Rat Cerebral Cortex

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Protective Effects of Centella asiatica on Cognitive Deficits Induced by D-gal/AlCl3 via Inhibition of Oxidative Stress and Attenuation of Acetylcholinesterase Level

Toxics ◽

10.3390/toxics7020019 ◽

2019 ◽

Vol 7 (2) ◽

pp. 19 ◽

Cited By ~ 7

Author(s):

Samaila Chiroma ◽

Mohamad Baharuldin ◽

Che Mat Taib ◽

Zulkhairi Amom ◽

Saravanan Jagadeesan ◽

...

Keyword(s):

Oxidative Stress ◽

Cerebral Cortex ◽

Prefrontal Cortex ◽

Cognitive Deficits ◽

Neurodegenerative Disorder ◽

Centella Asiatica ◽

Morris Water Maze Test ◽

Enzyme Linked Immunosorbent Assay ◽

Protective Effects ◽

Ultrastructural Alteration

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with cholinergic dysfunctions and impaired redox homeostasis. The plant Centella asiatica (CA) is renowned for its nutritional benefits and herbal formulas for promoting health, enhancing cognition, and its neuroprotective effects. The present study aims to investigate the protective role of CA on D-gal/AlCl3-induced cognitive deficits in rats. The rats were divided into six groups and administered with donepezil 1 mg/kg/day, CA (200, 400, and 800 mg/kg/day) and D-gal 60 mg/kg/day + AlCl3 200 mg/kg/day for 10 weeks. The ethology of the rats was evaluated by the Morris water maze test. The levels of acetylcholinesterase (AChE), phosphorylated tau (P-tau), malondialdehyde (MDA) and activities of superoxide dismutase (SOD), in the hippocampus and cerebral cortex were estimated by enzyme-linked immunosorbent assay (ELISA). Additionally, the ultrastructure of the prefrontal cortex of the rats’ was observed using transmission electron microscopy (TEM). Rats administered with D-gal/AlCl3 exhibited cognitive deficits, decreased activities of SOD, and marked increase in AChE and MDA levels. Further, prominent alterations in the ultrastructure of the prefrontal cortex were observed. Conversely, co-administration of CA with D-gal/AlCl3 improved cognitive impairment, decreased AChE levels, attenuated the oxidative stress in hippocampus and cerebral cortex, and prevented ultrastructural alteration of neurons in the prefrontal cortex. Irrespective of the dose of CA administered, the protective effects were comparable to donepezil. In conclusion, this study suggests that CA attenuated the cognitive deficits in rats by restoring cholinergic function, attenuating oxidative stress, and preventing the morphological aberrations.

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