Solid Lipid Curcumin Particles Protect Medium Spiny Neuronal Morphology, and Reduce Learning and Memory Deficits in the YAC128 Mouse Model of Huntington’s Disease

Abstract

Huntington’s disease (HD) is a genetic neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms, accompanied by massive neuronal degeneration in the striatum. In this study, we utilized solid lipid curcumin particles (SLCPs) and solid lipid particles (SLPs) to test their efficacy in reducing deficits in YAC128 HD mice. Eleven-month-old YAC128 male and female mice were treated orally with SLCPs (100 mg/kg) or equivalent volumes of SLPs or vehicle (phosphate-buffered saline) every other day for eight weeks. Learning and memory performance was assessed using an active-avoidance task on week eight. The mice were euthanized, and their brains were processed using Golgi-Cox staining to study the morphology of medium spiny neurons (MSNs) and Western blots to quantify amounts of DARPP-32, brain-derived neurotrophic factor (BDNF), TrkB, synaptophysin, and PSD-95. We found that both SLCPs and SLPs improved learning and memory in HD mice, as measured by the active avoidance task. We also found that SLCP and SLP treatments preserved MSNs arborization and spinal density and modulated synaptic proteins. Our study shows that SLCPs, as well as the lipid particles, can have therapeutic effects in old YAC128 HD mice in terms of recovering from HD brain pathology and cognitive deficits.

The pharmacological basis of the curcumin nutraceutical uses: an update

“…Moreover, Pepe et al recently demonstrated that nano-sized curcumin prevented huntingtin-mediated apoptosis in striatal derived cells (296). Elifani and Gharaibeh reported an ameliorated phenotype in HD murine models after oral administration of curcumin: in line with the scientific literature, both the authors observed the activation of pathways involved in BDNF expression, such as TrkB, Erk, and Akt (292,297). Moreover, the authors investigated the impact of curcumin on gastrointestinal disturbs resembled in the R6/2 mice model of HD, which cause weight loss and cachexia: the authors observed a recovery in body weight and intestinal function.…”

Curcugreen Treatment Prevented Splenomegaly and Other Peripheral Organ Abnormalities in 3xTg and 5xFAD Mouse Models of Alzheimer’s Disease

“…As immune reaction is prominent in AD mice, we were interested in reducing the immune reaction by anti-inflammatory natural compounds called curcuminoids, which include Cur, bisdemethoxycurcumin (BDMC), and demethoxycurcumin (DMC). We used CGR which contains 86% of curcuminoids, and these compounds have been shown to have strong anti-inflammatory properties, as reported by many investigators [21,22], including the results from our own laboratory [23][24][25][26][27][28][29]. There are certain advantages to use CGR for our study: (i) it is more water soluble (Figure 1A); (ii) it is 700% more potent than natural turmeric; and (iii) it can stay for a longer period (8-10 h) in the systemic circulation in comparison to the natural curcuminoids, when administered orally.…”

“…One natural compound, curcumin (Cur) has antioxidant, anti-inflammatory, and antiamyloid properties, and has been extensively investigated, including thorough work in our own laboratory, as a potential treatment for AD [21][22][23][24][25][26][27][28][29]. The most active compound in turmeric (a root of the herb Curcuma longa) is Cur and other important compounds are bismisthoxycurcumin (BMC) and debismethoxycurcumin (DBMC).…”

“…The most active compound in turmeric (a root of the herb Curcuma longa) is Cur and other important compounds are bismisthoxycurcumin (BMC) and debismethoxycurcumin (DBMC). These three compounds, together, are known as curcuminoids, can cross the blood brain barrier (BBB), penetrate into brain cells, and protect neurons from Aβ-induced neuronal death [25,29]. These compounds are hydrophobic or lipophilic in nature, but possess poor solubility in most body fluids, limiting their bioavailability.…”

“…Therefore, many investigators have developed different lipids or nano-conjugated formulations to increase their bioavailability. For example, solid lipid curcumin particles (SLCP) have been shown to prevent neuropathology in AD and other neurodegenerative diseases [25,26,29,30]. More recently, we have been investigating the effects of curcugreen (CGR) on animal models of AD.…”