| Title |
Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice
|
|---|---|
| Published in |
Cellular and Molecular Life Sciences, October 2015
|
| DOI | 10.1007/s00018-015-2057-1 |
| Pubmed ID | |
| Authors |
Jian Xu, Pradeep Kurup, Tyler D. Baguley, Ethan Foscue, Jonathan A. Ellman, Angus C. Nairn, Paul J. Lombroso |
| Abstract |
Brain-derived neurotrophic factor (BDNF) and STriatal-Enriched protein tyrosine Phosphatase 61 (STEP61) have opposing functions in the brain, with BDNF supporting and STEP61 opposing synaptic strengthening. BDNF and STEP61 also exhibit an inverse pattern of expression in a number of brain disorders, including schizophrenia (SZ). NMDAR antagonists such as phencyclidine (PCP) elicit SZ-like symptoms in rodent models and unaffected individuals, and exacerbate psychotic episodes in SZ. Here we characterize the regulation of BDNF expression by STEP61, utilizing PCP-treated cortical culture and PCP-treated mice. PCP-treated cortical neurons showed both an increase in STEP61 levels and a decrease in BDNF expression. The reduction in BDNF expression was prevented by STEP61 knockdown or use of the STEP inhibitor, TC-2153. The PCP-induced increase in STEP61 expression was associated with the inhibition of CREB-dependent BDNF transcription. Similarly, both genetic and pharmacologic inhibition of STEP prevented the PCP-induced reduction in BDNF expression in vivo and normalized PCP-induced hyperlocomotion and cognitive deficits. These results suggest a mechanism by which STEP61 regulates BDNF expression, with implications for cognitive functioning in CNS disorders. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 34 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 34 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 8 | 24% |
| Student > Bachelor | 6 | 18% |
| Student > Doctoral Student | 4 | 12% |
| Student > Master | 4 | 12% |
| Student > Postgraduate | 3 | 9% |
| Other | 3 | 9% |
| Unknown | 6 | 18% |
| Readers by discipline | Count | As % |
|---|---|---|
| Neuroscience | 8 | 24% |
| Agricultural and Biological Sciences | 6 | 18% |
| Biochemistry, Genetics and Molecular Biology | 3 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
| Chemistry | 2 | 6% |
| Other | 8 | 24% |
| Unknown | 5 | 15% |
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 10 October 2015.
All research outputs
#21,141,111
of 23,794,258 outputs
Outputs from Cellular and Molecular Life Sciences
#3,769
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Outputs of similar age
#235,405
of 279,655 outputs
Outputs of similar age from Cellular and Molecular Life Sciences
#50
of 56 outputs
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