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

• Published in: International journal of molecular sciences Vol. 21; no. 24; p. 9542
• Main Authors: Gharaibeh, Abeer, Maiti, Panchanan, Culver, Rebecca, Heileman, Shiela, Srinageshwar, Bhairavi, Story, Darren, Spelde, Kristin, Paladugu, Leela, Munro, Nikolas, Muhn, Nathan, Kolli, Nivya, Rossignol, Julien, Dunbar, Gary L
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 15-12-2020; MDPI
• Subjects: Animals; Avoidance; Bioavailability; Biomarkers; Brain; Brain-derived neurotrophic factor; Brain-Derived Neurotrophic Factor - metabolism; Curcumin; Curcumin - administration & dosage; DARPP-32 protein; Degeneration; Dendritic Spines - drug effects; Dendritic Spines - metabolism; Disease; Disease Models, Animal; Dopamine and cAMP-Regulated Phosphoprotein 32 - metabolism; Huntington Disease - etiology; Huntington Disease - metabolism; Huntington Disease - psychology; Huntington's disease; Huntingtons disease; Learning; Learning - drug effects; Lipids; Liposomes; Memory; Memory - drug effects; Memory Disorders - drug therapy; Memory Disorders - etiology; Memory Disorders - metabolism; Mice; Mice, Transgenic; Morphology; MSNs; Neostriatum; Neurodegeneration; Neurons - drug effects; Neurons - metabolism; Neurons - pathology; Postsynaptic density proteins; Proteins; Receptor, trkB - metabolism; Signs and symptoms; Spiny neurons; Synaptic density; Synaptophysin; TrkB receptors; Western blotting; YAC128; lipids; Huntington’s disease; YAC128; MSNs; curcumin
• DOI: 10.3390/ijms21249542
• EISSN: 1422-0067
• ISSN: 1422-0067; 1661-6596

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.