Curcumin Exerts Neuroprotective Effects Against Homocysteine Intracerebroventricular Injection-Induced Cognitive Impairment and Oxidative Stress in Rat Brain

Abstract

Aging is the major risk factor for neurodegenerative diseases and oxidative stress and is involved in their pathophysiology. Oxidative stress can induce neuronal damage and modulate intracellular signaling, ultimately leading to neuronal death by apoptosis or necrosis. In this study we investigated the neuroprotective properties of the natural polyphenolic antioxidant compound, curcumin, against homocysteine (Hcy) neurotoxicity. Curcumin (5, 15, or 45 mg/kg) was injected intraperitoneally once daily for a period of 10 days beginning 5 days prior to Hcy (0.2 micromol/microl) intracerebroventricular injection in rats. Biochemical and behavioral studies, including passive avoidance learning and locomotor activity tests, were evaluated 24 hours after the last injection of curcumin or vehicle. Results indicated that Hcy induces lipid peroxidation and increases malondialdehyde (MDA) and superoxide anion (SOA) levels in whole rat brain. In addition, Hcy impaired memory retention in the passive avoidance learning test. However, curcumin treatment significantly decreased MDA and SOA levels and improved learning and memory in rats. These results suggest that Hcy may induce lipid peroxidation in rat brain and that polyphenol treatment (curcumin) improves learning and memory deficits by protecting the nervous system against oxidative stress.

Neurotoxic Agent-Induced Injury in Neurodegenerative Disease Model: Focus on Involvement of Glutamate Receptors

“…In several animal model studies, Hcy brought about synaptic dysfunction, oxidative stress, neurochemical imbalance, and apoptosis, resulting in cognitive impairment and neuronal cell death. Thus, an Hcy-induced neurotoxicity model might be suitable for the study of AD (Ataie et al, 2010a,b,c; Wei et al, 2014; Kamat et al, 2016; Li T. et al, 2017). Hcy has been shown to modulate glutamate receptors, which leads to various neurotoxic effects.…”

Polyphenol compounds and PKC signaling

“…Not only is it used as a spice to give a specific flavor and yellow color to curry, which is consumed in trace quantities daily by millions of people, curcumin has also been used as traditional medicine for liver disease (jaundice), indigestion, urinary tract diseases, rheumatoid arthritis, and insect bites [97–99]. Curcumin is a promising therapeutic agent for diseases such as cancer, diabetes, multiple sclerosis, Alzheimer's, HIV and cardiovascular disease [100–102]. …”

Betaine prevents homocysteine-induced memory impairment via matrix metalloproteinase-9 in the frontal cortex

“…Hcy also alters hippocampal plasticity and synaptic transmission resulting in learning and memory deficits [8,9]. Because elevated plasma Hcy levels known as hyperhomocysteinemia (HHcy) contribute to neurodegenerative diseases [10,11], homocysteine-decreasing therapies are potentially beneficial.…”