Document Detail

Sex differences in the activity of signalling pathways and expression of G-protein-coupled receptor kinases in the neonatal ventral hippocampal lesion model of schizophrenia.
MedLine Citation:
PMID:  20158934     Owner:  NLM     Status:  MEDLINE    
Animals with the neonatal ventral hippocampal lesion (NVHL) demonstrate altered responsiveness to stress and various drugs reminiscent of that in schizophrenia. Post-pubertal onset of abnormalities suggests the possibility of sex differences in NVHL effects that may model sex differences in schizophrenia. Here we demonstrate that novelty- and MK-801-induced hyperactivity is evident in both male and female NVHL rats, whereas only NVHL males were hyperactive in response to apomorphine. Next, we examined the sex- and NVHL-dependent differences in the activity of the ERK and Akt pathways. The basal activity of both pathways was higher in females than in males. NVHL reduces the level of phosphorylation of ERK1/2, Akt, and GSK-3 in both sexes, although males show more consistent down-regulation. Females had higher levels of G-protein-coupled kinases [G-protein-coupled receptor kinase (GRK)] 3 and 5, whereas the concentrations of other GRKs and arrestins were the same. In the nucleus accumbens, the concentration of GRK5 in females was elevated by NVHL to the male level. The data demonstrate profound sex differences in the expression and activity of signalling molecules that may underlie differential susceptibility to schizophrenia.
Evgeny Bychkov; M Rafiuddin Ahmed; Eugenia V Gurevich
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-02-17
Journal Detail:
Title:  The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)     Volume:  14     ISSN:  1469-5111     ISO Abbreviation:  Int. J. Neuropsychopharmacol.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2010-12-01     Completed Date:  2011-05-24     Revised Date:  2014-09-20    
Medline Journal Info:
Nlm Unique ID:  9815893     Medline TA:  Int J Neuropsychopharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1-15     Citation Subset:  IM    
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MeSH Terms
Animals, Newborn
Apomorphine / pharmacology
Disease Models, Animal
Dizocilpine Maleate / pharmacology
Excitatory Amino Acid Antagonists / pharmacology
G-Protein-Coupled Receptor Kinases / biosynthesis*,  metabolism
HEK293 Cells
Hippocampus / metabolism*
Mitogen-Activated Protein Kinase 3 / biosynthesis,  metabolism
Motor Activity / drug effects*
Proto-Oncogene Proteins c-akt / biosynthesis,  metabolism
Rats, Sprague-Dawley
Schizophrenia / genetics,  metabolism*
Sex Characteristics*
Signal Transduction*
Grant Support
NS45117/NS/NINDS NIH HHS; R01 NS045117/NS/NINDS NIH HHS; R01 NS045117-01A1/NS/NINDS NIH HHS; R01 NS045117-02/NS/NINDS NIH HHS; R01 NS045117-03/NS/NINDS NIH HHS; R01 NS045117-04/NS/NINDS NIH HHS; R01 NS045117-05/NS/NINDS NIH HHS
Reg. No./Substance:
0/Excitatory Amino Acid Antagonists; 6LR8C1B66Q/Dizocilpine Maleate; EC Proteins c-akt; EC Receptor Kinases; EC Protein Kinase 3; N21FAR7B4S/Apomorphine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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