Striatal Interneurons in Transgenic Nonhuman Primate Model of Huntington’s Disease.

Striatal Interneurons in Transgenic Nonhuman Primate Model of Huntington’s Disease.

Publication date: Mar 05, 2019

Huntington’s disease is an autosomal dominant neurodegenerative disorder associated with progressive motor and cognitive impairments, and the expansion of a cysteine-adenine-guanine trinucleotide (polyglutamine) repeats in exon one of the human huntingtin gene. The pathology of the disease is characterized by a profound degeneration of striatal GABAergic projection neurons with relative sparing of interneurons accompanied with astrogliosis. Here, we describe the striatal pathology in two genotypically different transgenic HD monkeys that exhibit degrees of disease progression that resembled those seen in juvenile- (rHD1) and adult-onset (rHD7) HD. The caudate nucleus and putamen underwent severe neuronal loss in both animals, while the striatal volume was reduced only in rHD1, the most severely affected monkey. The number of GABAergic (calretinin- and parvalbumin-positive) and cholinergic interneurons was also reduced in most striatal regions of these two monkeys, but to variable degrees. Overall, the density of interneurons was increased in rHD1, but not in rHD7, suggesting a relative sparing of interneurons over projection neurons in the striatum of the most affected HD monkey. The neuropil of both the caudate nucleus and putamen was invaded with reactive astrocytes in rHD1, while astrogliosis was much less severe in rHD7 and absent from control. Combined with behavioral data collected from these monkeys, our findings further demonstrate that transgenic HD monkeys share similar disease patterns with HD patients, making them a highly reliable preclinical HD animal model.

Open Access PDF

Lallani, S.B., Villalba, R.M., Chen, Y., Smith, Y., and Chan, A.W.S. Striatal Interneurons in Transgenic Nonhuman Primate Model of Huntington’s Disease. 06383. 2019 Sci Rep (9):1.

Concepts Keywords
Adenine Caudate nucleus
Astrocytes Parvalbumin
Astrogliosis Interneuron
Autosomal Dominant Putamen
Caudate Nucleus Striatum
Cholinergic Neuroscience
Cognitive Branches of biology
Cysteine Human anatomy
Exon Basal ganglia
GABAergic Neurodegenerative disorder
Gene
Genotypically
Guanine
Huntingtin
Huntington
Interneurons
Monkey
Neurodegenerative Disorder
Neurons
Neuropil
Parvalbumin
Pathology
Primate
Progressive
Putamen
Sci
Striatal
Striatum
Transgenic

Semantics

Type Source Name
disease MESH disease progression
drug DRUGBANK Guanine
drug DRUGBANK Adenine
disease MESH neurodegenerative disorder
disease MESH cognitive impairments
drug DRUGBANK L-Cysteine
pathway BSID Reproduction
gene UNIPROT LAT2
gene UNIPROT EHD1
drug DRUGBANK Etoperidone
gene UNIPROT DECR1
drug DRUGBANK Somatostatin
drug DRUGBANK Neuropeptide Y
gene UNIPROT COMP
gene UNIPROT ZBTB8OS
drug DRUGBANK Calcium
gene UNIPROT MBNL1
gene UNIPROT ACTA1
gene UNIPROT DST
disease DOID anxiety
disease MESH anxiety
disease DOID Huntington Disease
disease MESH Huntington Disease
gene UNIPROT BRD2
gene UNIPROT AQP3
gene UNIPROT FURIN
gene UNIPROT SSRP1
gene UNIPROT LARGE1
gene UNIPROT NT5E
gene UNIPROT NR1H4
gene UNIPROT ADRB2
gene UNIPROT BFAR
drug DRUGBANK Flunarizine
gene UNIPROT HDAC7
gene UNIPROT HDAC9
gene UNIPROT FANCE
gene UNIPROT ELOVL6
disease DOID face
gene UNIPROT CR2
gene UNIPROT PPHLN1
gene UNIPROT TDGF1
gene UNIPROT CALB2
gene UNIPROT CD55
gene UNIPROT DHRS4
gene UNIPROT RELA
gene UNIPROT NEU1
gene UNIPROT ERBB2
gene UNIPROT NEURL1
gene UNIPROT GRAP2
gene UNIPROT DEPP1
gene UNIPROT GOPC
disease MESH separated
gene UNIPROT VSIR
gene UNIPROT TNFSF14
drug DRUGBANK Ethanol
drug DRUGBANK Hydrogen peroxide
drug DRUGBANK Imidazole
drug DRUGBANK Tromethamine
gene UNIPROT ABCB6
drug DRUGBANK Abacavir
drug DRUGBANK Biotin
drug DRUGBANK Human Serum Albumin
gene UNIPROT GFAP
gene UNIPROT SH2D3C
gene UNIPROT CHAT
drug DRUGBANK Choline
drug DRUGBANK Glycerin
drug DRUGBANK Sucrose
drug DRUGBANK Nitrogen
gene UNIPROT SNAP25
gene UNIPROT SLC35G1
gene UNIPROT TSPO
gene UNIPROT CHRM3
drug DRUGBANK Formaldehyde
drug DRUGBANK Pentobarbital
gene UNIPROT FOXD3
gene UNIPROT CYREN
disease MESH development
gene UNIPROT HTT
drug DRUGBANK Coenzyme M

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