Phosphodiesterase 10A inhibition is associated with locomotor and cognitive deficits and increased anxiety in mice

@article{Hebb2008Phosphodiesterase1I,
  title={Phosphodiesterase 10A inhibition is associated with locomotor and cognitive deficits and increased anxiety in mice},
  author={Andrea L. O. Hebb and Harold A. Robertson and Eileen M. Denovan‐Wright},
  journal={European Neuropsychopharmacology},
  year={2008},
  volume={18},
  pages={339-363}
}
Phosphodiesterase 10A (PDE10A) mRNA and protein levels decline in the striatum of R6/1 and R6/2 Huntington's disease (HD) mice prior to motor symptom development. In human HD, PDE10A protein levels are significantly decreased in the caudate-putamen of patients with grade 3 HD compared to age-matched controls. To test whether the loss of PDE10A activity in the striatum was detrimental to normal brain function, we treated wild-type (WT) mice with chronic administration of papaverine, which is a… Expand
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Papaverine inhibits α-synuclein aggregation by modulating neuroinflammation and matrix metalloproteinase-3 expression in the subacute MPTP/P mouse model of Parkinson's disease.
  • Y. Leem, Jin-Sun Park, Jung-Eun Park, Do-Yeon Kim, Jihee Lee Kang, Hee-Sun Kim
  • Medicine
  • Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
  • 2020
TLDR
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References

SHOWING 1-10 OF 71 REFERENCES
Genetic deletion of the striatum-enriched phosphodiesterase PDE10A: Evidence for altered striatal function
TLDR
The findings suggest that PDE10A is involved in regulating striatal output, possibly by reducing the sensitivity of medium spiny neurons to glutamatergic excitation, and presents a novel treatment for psychosis. Expand
Inhibition of the striatum-enriched phosphodiesterase PDE10A: A novel approach to the treatment of psychosis
TLDR
The results indicate that PDE10A regulates the activation of striatal medium spiny neurons through effects on cAMP- and cGMP-dependent signaling cascades and demonstrate that papaverine has efficacy in behavioral models predictive of antipsychotic activity. Expand
Striatal phosphodiesterase mRNA and protein levels are reduced in Huntington′s disease transgenic mice prior to the onset of motor symptoms
TLDR
The finding that steady-state mRNA levels of two members of the phosphodiesterase (PDE) multi-gene family decrease over time in the striatum of R6 transgenic HD mice relative to age-matched wild-type littermates suggests that the regulation of PDE10A and PDE1B, but not PDE4A, mRNA levels is dependent on the relative expression of or number of CAG repeats within the human HD transgene. Expand
Beneficial effects of rolipram in a quinolinic acid model of striatal excitotoxicity
TLDR
Rolipram showed to be effective in increasing significantly the levels of activated CREB in the striatal spiny neurons, which accounts mostly for its beneficial effect in the authors' rodent model of excitotoxicity. Expand
Phosphodiesterase 10A inhibitors: a novel approach to the treatment of the symptoms of schizophrenia.
TLDR
By enhancing corticostriatal signaling, PDE10A inhibitors have the potential to improve some of the cognitive symptoms of schizophrenia and are consistent with their potential as antipsychotic agents. Expand
Specific progressive cAMP reduction implicates energy deficit in presymptomatic Huntington's disease knock-in mice.
TLDR
It is suggested that impaired ATP synthesis and diminished cAMP levels amplify the early HD disease cascade by decreasing CRE-regulated gene transcription and altering energy dependent processes essential to neuronal cell survival. Expand
Animal Model of Schizophrenia
TLDR
The repeatedPCP treatment impaired NMDA receptor function and decreased levels of spontaneous extracellular glutamate in the prefrontal cortex, indicating that the repeated PCP treatment impairs both pre‐ and postsynaptic glutamate transmissions. Expand
Phosphodiesterase inhibitors for cognitive enhancement.
TLDR
Evidence demonstrating that rolipram, a selective inhibitor of cAMP-selective PDE4 enzymes, has positive effects on learning and memory in animal models is summarized to provide support for the general approach of second messenger modulation as a potential therapy for cognitive dysfunction and suggest that PDE 4 inhibitors may have utility for improving the symptoms of cognitive decline associated with neurodegenerative and psychiatric diseases. Expand
Striking changes in anxiety in Huntington's disease transgenic mice
TLDR
The results indicated that some of the reduced anxiety of Huntington's disease transgenic mice could be attributed to the presence of an endogenous anxiolytic ligand. Expand
Effect of sildenafil on anxiety in the plus-maze test in mice.
TLDR
Results suggest that a nitric oxide-cGMP pathway seems to play an important role in sildenafil-induced anxiogenic-like effect. Expand
...
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3
4
5
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