Curcumin improves spatial memory impairment induced by human immunodeficiency virus type 1 glycoprotein 120 V3 loop peptide in rats

Abstract

Aims

Human immunodeficiency virus-1 (HIV-1)-associated dementia (HAD) is a significant consequence of HIV infection. Although highly active antiretroviral therapy (HAART) has dramatically decreased HIV-1 load in acquired immune deficiency syndrome (AIDS) patients, HAART does not completely protect against the development of HAD, therefore novel strategies for the prevention and treatment are urgently needed. In this study, we chose curcumin which has a neuroprotective role and tested the effect against neuron damage induced by HIV-1gp120 V3 loop peptide.

Main methods

Rats were given 150 ng gp120 V3 peptide by intracerebroventricular (ICV) infusion for 3 days to establish the cognitive dysfunction model. After recovery from the surgery, the rats in treatment groups were given curcumin by intragastric infusion for 2 weeks. Subsequently, we used the Morris water maze test, long-term potentiation (LTP) recording, biochemical measurement of oxidative damage, Nissl staining, and BDNF immunostaining to evaluate the neuropathological changes and the effect of curcumin on rats.

Key findings

Our results documented that the gp120 V3 peptide induced impairment of spatial learning and memory, inhibited LTP in the CA1 region of the hippocampus, and mediated oxidative stress and neuronal injury. These impairments were ameliorated by intragastric infusion of curcumin.

Significance

These results suggested that dietary supplementation of curcumin may be a potential therapeutic strategy for the treatment and/or prevention of HAD.

Introduction

Over the past two decades, acquired immune deficiency syndrome (AIDS) caused by human immunodeficiency virus-1 (HIV-1) has emerged as one of the most visible and important health concerns worldwide. HIV-1 enters the central nervous system (CNS) at an early stage (Chakrabarti et al., 1991, Davis et al., 1992), which causes significant damage in the nervous system during the disease course of AIDS. That eventually leads to a variety of progressive neurological disorders, including HIV-1-associated dementia (HAD). HAD is characterized by deterioration of cognitive and motor functions and behavioral changes (Navia et al., 1986, Price et al., 1988).

Even though HAD incidence has decreased to less than 10% of AIDS patients with the use of highly active antiretroviral therapy (HAART) (Dore et al., 1999, Sacktor et al., 2001), HAD still is a significant complication of advanced HIV-1 disease.

Extensive data suggest that the cognitive impairments seen in AIDS patients are associated with the brain infiltration of HIV-1 infected mononuclear phagocytes (MP; perivascular brain macrophages and microglia) (Glass et al. 1995) and the resulting release of soluble viral (e.g. HIV-1gp120) and cellular factors (such as proinflammatory cytokines). These soluble factors induce neuronal apoptosis (Adle-Biassette et al., 1995, Gelbard et al., 1995, Petito and Roberts, 1995), reduction in synaptic and dendritic densities (Everall et al., 1999, Fox et al., 1997), and selective neuronal loss (Fox et al., 1997, Masliah et al., 1992). However, the molecular and cellular pathogenesis of HAD is not understood. Therefore, understanding of the underlying mechanisms by which HIV-1 causes HAD and an exploration of a new approach for the treatment of HAD is imperative (Bouwman et al., 1998, Langford et al., 2003, Sacktor et al., 2002).

Curcumin, a principal curcuminoid of the Indian curry spice turmeric, has been widely used for centuries in indigenous medicine for the treatment of a variety of inflammatory conditions and diseases. It has a wide range of pharmacological properties, including anti-inflammatory (Satoskar et al., 1986, Sandur et al., 2007), anti-cancer (Kuttan et al., 1985, Anand et al., 2008), anti-oxidant (Manikandan et al., 2004, Toda et al., 1985), wound healing (Sidhu et al. 1999), and anti-microbial effects (Negi et al. 1999). Dietary supplementation with curcumin is beneficial in neurodegenerative disorders such as Alzheimer's disease (Calabrese et al., 2003, Yang et al., 2005). In a focal cerebral ischemia model of rats, curcumin offers significant neuron protection through the inhibition of lipid peroxidation, an increase in endogenous antioxidant defense enzymes, and a reduction in peroxynitrite formation (Thiyagarajan and Sharma 2004). Therefore, we hypothesize that curcumin may be able to treat or prevent HAD by a reduction in HIV-induced neurotoxicity. To test this hypothesis, we evaluated the neuron protective effects of curcumin in rats with cognitive deficits induced by the intracerebroventricular (ICV) injection of HIV-1 gp120 V3 loop peptide.