| 1 | Arch. Gen. Psychiatry 2011 Jan 68: 21-31 |
|---|---|
| PMID | 20819979 |
| Title | Altered expression of regulators of the cortical chloride transporters NKCC1 and KCC2 in schizophrenia. |
| Abstract | Disturbances in markers of cortical ?-aminobutyric acid neurotransmission are a common finding in精神分裂症. The nature of ?-aminobutyric acid neurotransmission (hyperpolarizing or depolarizing) depends on the local intracellular chloride concentration. In the central nervous system, the intracellular chloride level is determined by the activity of 2 cation-chloride transporters, NKCC1 and KCC2. The activities of these transporters are in turn regulated by a network of serine-threonine kinases that includes OXSR1, STK39, and the WNK kinases WNK1, WNK3, andWNK4. To compare the levels of NKCC1, KCC2, OXSR1, STK39, WNK1, WNK3, andWNK4transcripts in prefrontal cortex area 9 between subjects with精神分裂症and healthy comparison subjects. Real-time quantitative polymerase chain reaction technique was used to measure transcript levels in the prefrontal cortex. Human brain specimens were obtained from autopsies conducted at the Allegheny County Medical Examiner's Office, Pittsburgh, Pennsylvania. Postmortem brain specimens from 42 subjects with精神分裂症and 42 matched healthy comparison subjects. Brain specimens from 18 macaque monkeys exposed to haloperidol, olanzapine, or sham long-term. Relative expression levels for NKCC1, KCC2, OXSR1, STK39, WNK1, WNK3, andWNK4transcripts compared with the mean expression level of 3 housekeeping transcripts. OXSR1 and WNK3 transcripts were substantially overexpressed in subjects with精神分裂症relative to comparison subjects. In contrast, NKCC1, KCC2, STK39, WNK1, andWNK4transcript levels did not differ between subject groups. OXSR1 and WNK3 transcript expression levels were not changed in antipsychotic-exposed monkeys and were not affected by potential confounding factors in the subjects with精神分裂症. In精神分裂症, increased expression levels, and possibly increased kinase activities, of OXSR1 and WNK3 may shift the balance of chloride transport by NKCC1 and KCC2 and alter the nature of ?-aminobutyric acid neurotransmission in the prefrontal cortex. |
| SCZ Keywords | 精神分裂症 |