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

Abeer Gharaibeh; Panchanan Maiti; Rebecca Culver; Shiela Heileman; Bhairavi Srinageshwar; Darren Story; Kristin Spelde; Leela Paladugu; Nikolas Munro; Nathan Muhn; Nivya Kolli; Julien Rossignol; Gary L Dunbar

doi:10.3390/ijms21249542

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

Int J Mol Sci. 2020 Dec 15;21(24):9542. doi: 10.3390/ijms21249542.

Authors

Abeer Gharaibeh^{1

2

3}, Panchanan Maiti^{1

2

4

5

6}, Rebecca Culver^{1

2}, Shiela Heileman^{1

2}, Bhairavi Srinageshwar^{1

2}, Darren Story^{1

4}, Kristin Spelde^{1

2}, Leela Paladugu^{1

2}, Nikolas Munro^{1

2}, Nathan Muhn^{1

2}, Nivya Kolli^{1

2}, Julien Rossignol^{1

2

7}, Gary L Dunbar^{1

2

4

5}

Affiliations

¹ Field Neurosciences Institute Laboratory for Restorative Neurology, Central Michigan University, Mt. Pleasant, MI 48859, USA.
² Program in Neuroscience, Central Michigan University, Mt. Pleasant, MI 48859, USA.
³ Insight Research Center, Insight Institute of Neurosurgery & Neuroscience, Flint, MI 48507, USA.
⁴ Department of Psychology, Central Michigan University, Mt. Pleasant, MI 48859, USA.
⁵ Field Neurosciences Institute, Ascension St. Mary's, Saginaw, MI 48604, USA.
⁶ College of Health and Human Services, Saginaw Valley State University, Saginaw, MI 48710, USA.
⁷ College of Medicine, Central Michigan University, Mount Pleasant, MI 48859, USA.

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.

Keywords: Huntington’s disease; MSNs; YAC128; curcumin; lipids.

MeSH terms

Animals
Biomarkers
Brain-Derived Neurotrophic Factor / metabolism
Curcumin / administration & dosage*
Dendritic Spines / drug effects
Dendritic Spines / metabolism
Disease Models, Animal
Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism
Huntington Disease / etiology
Huntington Disease / metabolism*
Huntington Disease / psychology*
Learning / drug effects
Liposomes*
Memory / drug effects*
Memory Disorders / drug therapy
Memory Disorders / etiology
Memory Disorders / metabolism
Mice
Mice, Transgenic
Neurons / drug effects*
Neurons / metabolism*
Neurons / pathology
Receptor, trkB / metabolism

Substances

Biomarkers
Brain-Derived Neurotrophic Factor
Dopamine and cAMP-Regulated Phosphoprotein 32
Liposomes
Receptor, trkB
Curcumin