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| Content Provider | Springer Nature Link |
|---|---|
| Author | Openshaw, R.L. Thomson, D.M. Penninger, J.M. Pratt, J.A. Morris, B.J. |
| Copyright Year | 2016 |
| Abstract | Members of the c-Jun N-terminal kinase (JNK) family of mitogen-activated protein (MAP) kinases, and the upstream kinase MKK7, have all been strongly linked with synaptic plasticity and with the development of the neocortex. However, the impact of disruption of this pathway on cognitive function is unclear.In the current study, we test the hypothesis that reduced MKK7 expression is sufficient to cause cognitive impairment.Attentional function in mice haploinsufficient for Map2k7 (Map2k7 +/− mice) was investigated using the five-choice serial reaction time task (5-CSRTT).Once stable performance had been achieved, Map2k7 +/− mice showed a distinctive attentional deficit, in the form of an increased number of missed responses, accompanied by a more pronounced decrement in performance over time and elevated intra-individual reaction time variability. When performance was reassessed after administration of minocycline—a tetracycline antibiotic currently showing promise for the improvement of attentional deficits in patients with schizophrenia—signs of improvement in attentional performance were detected.Overall, Map2k7 haploinsufficiency causes a distinctive pattern of cognitive impairment strongly suggestive of an inability to sustain attention, in accordance with those seen in psychiatric patients carrying out similar tasks. This may be important for understanding the mechanisms of cognitive dysfunction in clinical populations and highlights the possibility of treating some of these deficits with minocycline. |
| Starting Page | 293 |
| Ending Page | 305 |
| Page Count | 13 |
| File Format | |
| ISSN | 00333158 |
| Journal | Psychopharmacology |
| Volume Number | 234 |
| Issue Number | 2 |
| e-ISSN | 14322072 |
| Language | English |
| Publisher | Springer Berlin Heidelberg |
| Publisher Date | 2016-10-24 |
| Publisher Place | Berlin, Heidelberg |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Cognition Attention MKK7 JNK MAP kinase Neurosciences Pharmacology/Toxicology Psychiatry |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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