Effect of chronic treatment with the protein kinase C inhibitor staurosporine on the acquisition and expression of contextual fear conditioning

Li, Xiao Bai; Inoue, Takeshi; Koyama, Tsukasa

doi:10.1016/s0014-2999(02)01441-3

Cited by 11 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, the search for specific genetic factors that contribute to the pathophysiology of suicide has been challenging (Mann et al, 2009; Tsai et al, 2011). Previous studies with rodent models with fear and stress suggested that kinase genes in the brain may play a role in fear and stress-related behavior (Kouzu et al, 2000; Li et al, 2002; Revest et al, 2005; Sananbenesi et al, 2007; Hains et al, 2009). Although fear and stress may contribute to suicidal behavior in humans, expression profiles of those kinases genes in suicide brains have not been well-characterized.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies have suggested that these kinases such as PKC, CAMK, MAPK , and CDK also regulate fear conditioning and extinction in animals (Schafe et al, 2000; Li et al, 2002; Frankland et al, 2004; Lepicard et al, 2006; Sananbenesi et al, 2007; Bergstrom et al, 2011). For example, chronic administration of a PKC inhibitor reduced the acquisition of conditioned fear memory suggesting the involvement of PKC in the synaptic plasticity and memory (Li et al, 2002). On the contrary, another study reported that inhibition of PKC signaling protected dendritic spines in the PFC and rescued working memory impairment caused by chronic stress (Hains et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Analysis of Kinase Gene Expression in the Frontal Cortex of Suicide Victims: Implications of Fear and Stress†

Choi¹,

Le²,

Xing³

et al. 2011

Front. Behav. Neurosci.

View full text Add to dashboard Cite

Suicide is a serious public health issue that results from an interaction between multiple risk factors including individual vulnerabilities to complex feelings of hopelessness, fear, and stress. Although kinase genes have been implicated in fear and stress, including the consolidation and extinction of fearful memories, expression profiles of those genes in the brain of suicide victims are less clear. Using gene expression microarray data from the Online Stanley Genomics Database1 and a quantitative PCR, we investigated the expression profiles of multiple kinase genes including the calcium calmodulin-dependent kinase (CAMK), the cyclin-dependent kinase, the mitogen-activated protein kinase (MAPK), and the protein kinase C (PKC) in the prefrontal cortex (PFC) of mood disorder patients died with suicide (N = 45) and without suicide (N = 38). We also investigated the expression pattern of the same genes in the PFC of developing humans ranging in age from birth to 49 year (N = 46). The expression levels of CAMK2B, CDK5, MAPK9, and PRKCI were increased in the PFC of suicide victims as compared to non-suicide controls (false discovery rate, FDR-adjusted p < 0.05, fold change >1.1). Those genes also showed changes in expression pattern during the postnatal development (FDR-adjusted p < 0.05). These results suggest that multiple kinase genes undergo age-dependent changes in normal brains as well as pathological changes in suicide brains. These findings may provide an important link to protein kinases known to be important for the development of fear memory, stress associated neural plasticity, and up-regulation in the PFC of suicide victims. More research is needed to better understand the functional role of these kinase genes that may be associated with the pathophysiology of suicide.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Analysis of Kinase Gene Expression in the Frontal Cortex of Suicide Victims: Implications of Fear and Stress†

Choi¹,

Le²,

Xing³

et al. 2011

Front. Behav. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The region 2p25.1 contains the gene neurotensin receptor 2, which has an important physiological role in sensory perception [51]. Additionally, the region 2p21 contains the gene protein kinase C epsilon, which has been shown to be involved in neuronal channel activation and may be involved in emotional learning and memory [52]. These results demonstrate the efficacy of our approach, however they are subject to replication in future studies using the wealth of genetic and behavioral data collected in other linkage and association studies.…”

Section: Discussionmentioning

confidence: 99%

A Novel Analytical Framework for Dissecting the Genetic Architecture of Behavioral Symptoms in Neuropsychiatric Disorders

et al. 2010

View full text Add to dashboard Cite

BackgroundFor diagnosis of neuropsychiatric disorders, a categorical classification system is often utilized as a simple way for conceptualizing an often complex clinical picture. This approach provides an unsatisfactory model of mental illness, since in practice patients do not conform to these prototypical diagnostic categories. Family studies show notable familial co-aggregation between schizophrenia and bipolar illness and between schizoaffective disorders and both bipolar disorder and schizophrenia, revealing that mental illness does not conform to such categorical models and is likely to follow a continuum encompassing a spectrum of behavioral symptoms.Results and MethodologyWe introduce an analytic framework to dissect the phenotypic heterogeneity present in complex psychiatric disorders based on the conceptual paradigm of a continuum of psychosis. The approach identifies subgroups of behavioral symptoms that are likely to be phenotypically and genetically homogenous. We have evaluated this approach through analysis of simulated data with simulated behavioral traits and predisposing genetic factors. We also apply this approach to a psychiatric dataset of a genome scan for schizophrenia for which extensive behavioral information was collected for each individual patient and their families. With this approach, we identified significant evidence for linkage among depressed individuals with two distinct symptom profiles, that is individuals with sleep disturbance symptoms with linkage on chromosome 2q13 and also a mutually exclusive group of individuals with symptoms of concentration problems with linkage on chromosome 2q35. In addition we identified a subset of individuals with schizophrenia defined by language disturbances with linkage to chromosome 2p25.1 and a group of patients with a phenotype intermediate between those of schizophrenia and schizoaffective disorder with linkage to chromosome 2p21.ConclusionsThe findings presented are novel and demonstrate the efficacy of this approach in detection of genes underlying such complex human disorders as schizophrenia and depression.

show abstract

“…In addition, it had been demonstrated that the microinjection of a PKC and protein kinase A (PKA) inhibitor could block behavioral sensitization to cocaine (Steketee 1994). Staurosporine, a PKC inhibitor, could inhibit the acquisition of contextual fear conditioning (Li et al 2002). Furthermore, PKC inhibitors block neuroplastic changes in learning and memory processes (Reymann et al 1988;Malinow et al 1989).…”

Section: Introductionmentioning

confidence: 99%

“…Since the 2.5-mg/kg dose of METH induced delayed increases in the basal levels of glutamate in the NAc in our preliminary study, we administered staurosporine 120 min after METH injection to block the phenomena which are related to delayed increases in glutamate levels. The time course and the staurosporine dose were based on the analogous studies of Abekawa et al (2002) and Li et al (2002), respectively.…”

Section: Introductionmentioning

confidence: 99%

Effect of the protein kinase C inhibitor, staurosporine, on the high dose of methamphetamine-induced behavioral sensitization to dizocilpine (MK-801)

Fang

Abekawa

et al. 2005

Psychopharmacology

View full text Add to dashboard Cite

show abstract

Effect of chronic treatment with the protein kinase C inhibitor staurosporine on the acquisition and expression of contextual fear conditioning

Cited by 11 publications

References 33 publications

Analysis of Kinase Gene Expression in the Frontal Cortex of Suicide Victims: Implications of Fear and Stress†

Analysis of Kinase Gene Expression in the Frontal Cortex of Suicide Victims: Implications of Fear and Stress†

A Novel Analytical Framework for Dissecting the Genetic Architecture of Behavioral Symptoms in Neuropsychiatric Disorders

Effect of the protein kinase C inhibitor, staurosporine, on the high dose of methamphetamine-induced behavioral sensitization to dizocilpine (MK-801)

Contact Info

Product

Resources

About