Abstract
BackgroundProtein kinase C interacting protein (PKCI/HINT1) is a small protein belonging to the histidine triad (HIT) family proteins. Its brain immunoreactivity is located in neurons and neuronal processes. PKCI/HINT1 gene knockout (KO) mice display hyper-locomotion in response to D-amphetamine which is considered a positive symptom of schizophrenia in animal models. Postmortem studies identified PKCI/HINT1 as a candidate molecule for schizophrenia and bipolar disorder. We investigated the hypothesis that the PKCI/HINT1 gene may play an important role in regulating mood function in the CNS. We submitted PKCI/HINT1 KO mice and their wild type (WT) littermates to behavioral tests used to study anti-depressant, anxiety like behaviors, and goal-oriented behavior. Additionally, as many mood disorders coincide with modifications of hypothalamic-pituitary-adrenal (HPA) axis function, we assessed the HPA activity through measurement of plasma corticosterone levels.ResultsCompared to the WT controls, KO mice exhibited less immobility in the forced swim (FST) and the tail suspension (TST) tests. Activity in the TST tended to be attenuated by acute treatment with valproate at 300 mg/kg in KO mice. The PKCI/HINT1 KO mice presented less thigmotaxis in the Morris water maze and spent progressively more time in the lit compartment in the light/dark test. In a place navigation task, KO mice exhibited enhanced acquisition and retention. Furthermore, the afternoon basal plasma corticosterone level in PKCI/HINT1 KO mice was significantly higher than in the WT.ConclusionPKCI/HINT1 KO mice displayed a phenotype of behavioral and endocrine features which indicate changes of mood function, including anxiolytic-like and anti-depressant like behaviors, in conjunction with an elevated corticosterone level in plasma. These results suggest that the PKCI/HINT 1 gene could be important for the mood regulation function in the CNS.
Highlights
Protein kinase C interacting protein (PKCI/HINT1) is a small protein belonging to the histidine triad (HIT) family proteins
PKCI/HINT1 was recognized as a gene candidate in the neuropathology of bipolar disorder when its decreased expression in the dorsolateral prefrontal cortex was confirmed in a meta-analysis of 12 microarray studies of bipolar disorder [32]. They do not show any spontaneous hyperactivity in the open field test, PKCI/HINT1 KO mice present higher locomotor and stereotypic responses to the psychostimulant D-amphetamine than wild type (WT) controls
PKCI/HINT1 KO mice exhibited less immobility than their WT littermates in the forced swim and the tail suspension tests Immobility in the forced swim test is shown in Figure 1, where the PKCI/HINT1 KO mice were 2 times less immobile than their WT littermates at every stage of the test from day 1 to each of the trials in the four time periods of the second day, F(1,145) = 145.55, P < 0.0001 for genotype in a two-way ANOVA of trials × genotype
Summary
Protein kinase C interacting protein (PKCI/HINT1) is a small protein belonging to the histidine triad (HIT) family proteins. The biological study of mood disorders benefits from standardized animal behavioral tests that have been validated for their predictive validity for antidepressant and anxiolytic drugs. These tests are currently considered major tools for studying the function of targeted mutation in transgenic mice [2]. Open spaces in the open-field and in the Morris water maze serve as another index of anxietylike behavior based on the propensity of small rodents to avoid open areas In these paradigms anxiety-related behavior is assessed through the measure of thigmotaxis or wall-seeking behavior [13]. Genetic vulnerability to mania is believed to be expressed behaviorally as excessive goal pursuit [14] which can be modeled using goal-oriented behavioral tests
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
