Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

Birnbaum, Shari G.; Yuan, Peixiong; Wang, M.; Vijayraghavan, Susheel; BLOOM, AMY; Davis, Douglas J.; Gobeske, Kevin T.; Sweatt, J. David; Manji, H K; Arnsten, Amy F.T.

doi:10.1126/science.1100021

Cited by 277 publications

(289 citation statements)

References 17 publications

Supporting

Mentioning

267

Contrasting

Unclassified

Order By: Relevance

“…As reported in previous studies, brain NE system activation may stimulate arousal and contribute to execution of goal oriented actions (Frazer, 2000;Aston-Jones et al, 1991). On the other hand, NE has an inverted U-shaped influence on these behavioral outcomes (Birnbaum et al, 2004). Hence, it is possible that if the NE system is excessively stimulated, as for example in the mPFC, it may mediate disruption of these behaviors.…”

Section: Discussionmentioning

confidence: 91%

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

et al. 2013

View full text Add to dashboard Cite

a b s t r a c tPesticide exposure during brain development could represent an important risk factor for the onset of neurodegenerative diseases. Previous studies investigated the effect of permethrin (PERM) administered at 34 mg/kg, a dose close to the no observable adverse effect level (NOAEL) from post natal day (PND) 6 to PND 21 in rats. Despite the PERM dose did not elicited overt signs of toxicity (i.e. normal body weight gain curve), it was able to induce striatal neurodegeneration (dopamine and Nurr1 reduction, and lipid peroxidation increase). The present study was designed to characterize the cognitive deficits in the current animal model. When during late adulthood PERM treated rats were tested for spatial working memory performances in a T-maze-rewarded alternation task they took longer to choose for the correct arm in comparison to age matched controls. No differences between groups were found in anxiety-like state, locomotor activity, feeding behavior and spatial orientation task. Our findings showing a selective effect of PERM treatment on the T-maze task point to an involvement of frontal cortico-striatal circuitry rather than to a role for the hippocampus. The predominant disturbances concern the dopamine (DA) depletion in the striatum and, the serotonin (5-HT) and noradrenaline (NE) unbalance together with a hypometabolic state in the medial prefrontal cortex area. In the hippocampus, an increase of NE and a decrease of DA were observed in PERM treated rats as compared to controls. The concentration of the most representative marker for pyrethroid exposure (3-phenoxybenzoic acid) measured in the urine of rodents 12 h after the last treatment was 41.50 g/L and it was completely eliminated after 96 h.

show abstract

Section: Discussionmentioning

confidence: 91%

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

et al. 2013

View full text Add to dashboard Cite

show abstract

“…For instance, DAG metabolism, which is highly aberrant in diseased PFC, has been implicated in a number of synaptic processes including the regulation of dendritic spine morphology, plasticity, and neurotransmitter release (37). Importantly, overactivation of PKC, a target of DAG, interferes with PFC-regulated working memory (38), a key feature of AD. DAG accumulation in the PFC likely occurs through A␤-stimulated hydrolysis of PI(4,5)P 2 by PLC (10), based on the specific accumulation of polyunsaturated DAG 38:4 (supplemental Fig.…”

Section: Discussionmentioning

confidence: 99%

Comparative Lipidomic Analysis of Mouse and Human Brain with Alzheimer Disease

Chan

Oliveira

Cortés

et al. 2012

Journal of Biological Chemistry

480

505

View full text Add to dashboard Cite

“…Recently, Birnbaum and associates 198 demonstrated that excessive activation of PKC (including by stress)…”

Section: Protein Kinase C Signaling Cascade: a Shared Biochemical Tarmentioning

confidence: 99%

Neural circuitry and neuroplasticity in mood disorders: Insights for novel therapeutic targets

Carlson¹,

Singh²,

Zarate³

et al. 2006

NeuroRX

132

View full text Add to dashboard Cite

Summary:Major depressive disorder and bipolar disorder are severe mood disorders that affect the lives and functioning of millions each year. The majority of previous neurobiological research and standard pharmacotherapy regimens have approached these illnesses as purely neurochemical disorders, with particular focus on the monoaminergic neurotransmitter systems. Not altogether surprisingly, these treatments are inadequate for many individuals afflicted with these devastating illnesses. Recent advances in functional brain imaging have identified critical neural circuits involving the amygdala and other limbic structures, prefrontal cortical regions, thalamus, and basal ganglia that modulate emotional behavior and are disturbed in primary and secondary mood disorders. Growing evidence suggests that mechanisms of neural plasticity and cellular resilience, including impairments of neurotrophic signaling cascades as well as altered glutamatergic and glucocorticoid signaling, underlie the dysregulation in these circuits. The increasing ability to monitor and modulate activity in these circuits is beginning to yield greater insight into the neurobiological basis of mood disorders. Modulation of dysregulated activity in these affective circuits via pharmacological agents that enhance neuronal resilience and plasticity, and possibly via emerging nonpharmacologic, circuitry-based modalities (for example, deep brain stimulation, magnetic stimulation, or vagus nerve stimulation) offers promising targets for novel experimental therapeutics in the treatment of mood disorders.

show abstract

Protein Kinase C Overactivity Impairs Prefrontal Cortical Regulation of Working Memory

Cited by 277 publications

References 17 publications

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

Effects of early life permethrin exposure on spatial working memory and on monoamine levels in different brain areas of pre-senescent rats

Comparative Lipidomic Analysis of Mouse and Human Brain with Alzheimer Disease

Neural circuitry and neuroplasticity in mood disorders: Insights for novel therapeutic targets

Contact Info

Product

Resources

About