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Gating deficits in isolation-reared rats are correlated with alterations in protein expression in nucleus accumbens.
- Source :
-
Journal of neurochemistry [J Neurochem] 2009 Feb; Vol. 108 (3), pp. 611-20. Date of Electronic Publication: 2008 Nov 28. - Publication Year :
- 2009
-
Abstract
- The isolation-rearing (IR) paradigm, consisting of the social deprivation for 6-9 weeks after weaning, induces a spectrum of aberrant behaviors in adult rats. Some of these alterations such as sensorimotor gating deficits are reminiscent of the dysfunctions observed in schizophrenia patients. Although gating impairments in IR rats have been linked to impairments in the cortico-mesolimbic system, the specific molecular mechanisms underlying this relation are unclear. To elucidate the neurochemical modifications underlying the gating disturbances exhibited by IR rats, we compared their pre-pulse inhibition (PPI) of the acoustic startle reflex with that of socially reared (SR) controls, and correlated this index to the results of proteomic analyses in prefrontal cortex and nucleus accumbens from both groups. As expected, IR rats exhibited significantly lower startle amplitude and PPI than their SR counterparts. Following behavioral testing, IR and SR rats were killed and protein expression profiles of their brain regions were examined using two-dimensional electrophoresis based proteomics. Image analysis in the Coomassie blue-stained gel revealed that three protein spots were differentially expressed in the nucleus accumbens of IR and SR rats. Mass spectrometry (matrix-assisted laser desorption ionization-time of flight and MS/MS) identified these spots as heat shock protein 60 (HSP60), alpha-synuclein (alpha-syn), and 14-3-3 protein zeta/delta. While accumbal levels of HSP60 was decreased in IR rats, alpha-syn and 14-3-3 proteins were significantly increased in IR in comparison with SR controls. Notably, these two last alterations were significantly correlated with different loudness intensity-specific PPI deficits in IR rats. In view of the role of these proteins in synaptic trafficking and dopaminergic regulation, these findings might provide a neurochemical foundation for the gating alterations and psychotic-like behaviors in IR rats.
- Subjects :
- 14-3-3 Proteins metabolism
Animals
Brain Chemistry genetics
Brain Chemistry physiology
Data Interpretation, Statistical
Electrophoresis, Gel, Two-Dimensional
In Situ Hybridization
Mass Spectrometry
Prefrontal Cortex metabolism
Proteome genetics
Rats
Rats, Sprague-Dawley
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
alpha-Synuclein biosynthesis
alpha-Synuclein genetics
Behavior, Animal physiology
Nerve Tissue Proteins biosynthesis
Nucleus Accumbens metabolism
Reflex, Startle genetics
Reflex, Startle physiology
Schizophrenic Psychology
Social Isolation psychology
Subjects
Details
- Language :
- English
- ISSN :
- 1471-4159
- Volume :
- 108
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of neurochemistry
- Publication Type :
- Academic Journal
- Accession number :
- 19054277
- Full Text :
- https://doi.org/10.1111/j.1471-4159.2008.05806.x