Reduced activity and protein expression of NOS in R6/2 HD transgenic mice: effects of l-NAME on symptom progression

Deckel, A. Wallace; Gordinier, Ava; Nuttal, Diane; Tang, Vinsee; Kuwada, Clinton; Freitas, Rebecca de Oliveira; Gary, Keith A.

doi:10.1016/s0006-8993(01)03000-1

Cited by 44 publications

(40 citation statements)

References 43 publications

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“…9D)], in agreement with previous studies [38]. However, we did not find any changes in other proinflammatory parameters, such as the enzymes COX-2 or iNOS, and the cytokine IL-1β (data not shown), although this lack of response has been documented in the literature [39]. Treatment with CBG partially reversed the downregulation of PPARγ in R6/2 mice (Fig.…”

Section: Study Of Neuroprotective Effects Of Cbg In R6/2 Micesupporting

confidence: 93%

Neuroprotective Properties of Cannabigerol in Huntington's Disease: Studies in R6/2 Mice and 3-Nitropropionate-lesioned Mice

Navarrete²,

et al. 2015

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Different plant-derived and synthetic cannabinoids have shown to be neuroprotective in experimental models of Huntington's disease (HD) through cannabinoid receptordependent and/or independent mechanisms. Herein, we studied the effects of cannabigerol (CBG), a nonpsychotropic phytocannabinoid, in 2 different in vivo models of HD. CBG was extremely active as neuroprotectant in mice intoxicated with 3-nitropropionate (3NP), improving motor deficits and preserving striatal neurons against 3NP toxicity. In addition, CBG attenuated the reactive microgliosis and the upregulation of proinflammatory markers induced by 3NP, and improved the levels of antioxidant defenses that were also significantly reduced by 3NP. We also investigated the neuroprotective properties of CBG in R6/2 mice. Treatment with this phytocannabinoid produced a much lower, but significant, recovery in the deteriorated rotarod performance typical of R6/2 mice. Using HD array analysis, we were able to identify a series of genes linked to this disease (e.g., symplekin, Sin3a, Rcor1, histone deacetylase 2, huntingtin-associated protein 1, δ subunit of the gamma-aminobutyric acid-A receptor (GABA-A), and hippocalcin), whose expression was altered in R6/2 mice but partially normalized by CBG treatment. We also observed a modest improvement in the gene expression for brain-derived neurotrophic factor (BDNF), insulinlike growth factor-1 (IGF-1), and peroxisome proliferatoractivated receptor-γ (PPARγ), which is altered in these mice, as well as a small, but significant, reduction in the aggregation of mutant huntingtin in the striatal parenchyma in CBGtreated animals. In conclusion, our results open new research avenues for the use of CBG, alone or in combination with other phytocannabinoids or therapies, for the treatment of neurodegenerative diseases such as HD.

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Section: Study Of Neuroprotective Effects Of Cbg In R6/2 Micesupporting

confidence: 93%

Neuroprotective Properties of Cannabigerol in Huntington's Disease: Studies in R6/2 Mice and 3-Nitropropionate-lesioned Mice

Navarrete²,

et al. 2015

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“…For instance, a microarray study (Luthi-Carter et al, 2002) showed that the mRNA levels for CaMKII in the cortex of R6/2 HD mice were significantly reduced. Similarly, others have reported a reduction of CaMKII protein levels in a mouse model of HD (Deckel et al, 2001). Interestingly, neuronal intracellular inclusions, which are abundant in the HD cortex , recruit CREBbinding protein (Nucifora et al, 2001).…”

Section: Discussionmentioning

confidence: 75%

Deficits in Experience-Dependent Cortical Plasticity and Sensory-Discrimination Learning in Presymptomatic Huntington's Disease Mice

et al. 2005

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Huntington's disease (HD) is one of a group of neurodegenerative diseases caused by an expanded trinucleotide (CAG) repeat coding for an extended polyglutamine tract. The disease is inherited in an autosomal dominant manner, with onset of motor, cognitive, and psychiatric symptoms typically occurring in midlife, followed by unremitting progression and eventual death. We report here that motor presymptomatic R6/1 HD mice show a severe impairment of somatosensory-discrimination learning ability in a behavioral task that depends heavily on the barrel cortex. In parallel, there are deficits in barrel-cortex plasticity after a somatosensory whisker-deprivation paradigm. The present study demonstrates deficits in neocortical plasticity correlated with a specific learning impairment involving the same neocortical area, a finding that provides new insight into the cellular basis of early cognitive deficits in HD.

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“…Of the 68 proteins, four proteins were up-regulated, whereas the remaining 64 proteins were down-regulated in the striatum of HD mice. To the best of our knowledge, only seven of them (PKC␤II, calcium/calmodulin-dependent protein kinase type II, enolase, triose-phosphate isomerase, aconitase, creatine kinase, and cytochrome c) have been implicated in HD (27,(43)(44)(45)(46). Based on information obtained from protein knowledgebases of Swiss-Prot and TrEMBL (www.expasy.org), NCBI (www.ncbi.nlm.nih.gov/protein), European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI) (www.ebi.ac.uk/InterProScan), PSORT II (89), and PubMed (www.ncbi.nlm.nih.gov/PubMed), the differentially regulated proteins fall into 11 categories, excluding six proteins whose functions are unknown at this time (Table II).…”

Section: Resultsmentioning

confidence: 99%

Systematic Uncovering of Multiple Pathways Underlying the Pathology of Huntington Disease by an Acid-cleavable Isotope-coded Affinity Tag Approach

Chiang

Juo

Chang

et al. 2007

Molecular & Cellular Proteomics

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Huntington disease (HD) is an autosomal dominant neurodegenerative disease that results from a CAG (glutamine) trinucleotide expansion in exon 1 of huntingtin (Htt). The aggregation of mutant Htt has been implicated in the progression of HD. The earliest degeneration occurs in the striatum. To identify proteins critical for the progression of HD, we applied acid-cleavable ICAT technology to quantitatively determine changes in protein expressions in the striatum of a transgenic HD mouse model (R6/2). The cysteine residues of striatal proteins from HD and wild-type mice were labeled, respectively, with the heavy and light forms of the ICAT reagents. Samples were trypsinized, uncovered by avidin affinity chromatography, and analyzed by nano-LC-MS/MS. Western blot analyses were used to confirm and to calibrate the ICAT ratios. Linear regression was used to uncover a group of proteins that exhibited consistent changes. In two independent ICAT experiments, we identified 427 cysteine-containing striatal proteins among which ϳ66% (

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Reduced activity and protein expression of NOS in R6/2 HD transgenic mice: effects of l-NAME on symptom progression

Cited by 44 publications

References 43 publications

Neuroprotective Properties of Cannabigerol in Huntington's Disease: Studies in R6/2 Mice and 3-Nitropropionate-lesioned Mice

Neuroprotective Properties of Cannabigerol in Huntington's Disease: Studies in R6/2 Mice and 3-Nitropropionate-lesioned Mice

Deficits in Experience-Dependent Cortical Plasticity and Sensory-Discrimination Learning in Presymptomatic Huntington's Disease Mice

Systematic Uncovering of Multiple Pathways Underlying the Pathology of Huntington Disease by an Acid-cleavable Isotope-coded Affinity Tag Approach

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