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

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...

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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
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms21249542