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Surojit Paul Peter Olausson Deepa V Venkitaramani Irina Ruchkina Timothy D Moran Natalie Tronson Evan Mills Shawn Hakim Michael W Salter Jane R Taylor Paul J Lombroso 《Neuropsychopharmacology》2007,61(9):1049-1061
BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders. 相似文献
83.
Although anxiety is a well-established obstacle to the delivery of effective health care, there have been no attempts to measure it in the optometric consulting room. In this paper, we introduce physiological and psychological techniques that may be used to evaluate anxiety and arousal in the consulting room and present data from a small group of patients attending for a routine eye examination. Specifically, arousal was assessed before, during, and after the examination by measuring skin conductance in five patients. Anxiety was evaluated using the State-Trait Anxiety Inventory. Our data confirm the ability of these techniques to quantify arousal and anxiety in the optometric consulting room and reveal a previously unknown but important facet of the eye examination. We conclude that these techniques are suitable for use in further experimental work and may be used to identify factors capable of reducing anxiety in the optometric consulting room. 相似文献
84.
Jane Avery Serene Manzar Ashtari Philip R Szeszko Sanjiv Kumra 《Revue canadienne de psychiatrie》2007,52(3):135-145
OBJECTIVES: To critically review and integrate, from a developmental perspective, recent magnetic resonance imaging (MRI) studies of 4 childhood psychiatric disorders: schizophrenia, bipolar disorder (BD), attention-deficit hyperactivity disorder (ADHD), and major depressive disorder (MDD). METHOD: We reviewed published reports in refereed journals. We briefly describe the major findings with respect to the brain morphometry, chemistry, and function of children with psychiatric disorders and synthesize the reports in a summary to update clinicians. RESULTS: Some cortical grey matter abnormalities associated with schizophrenia appear to predate the onset of frank psychosis and continue to advance after the onset of psychosis, at least in more severe cases. Pediatric BD is associated with abnormalities in a circuit, thought to be involved in mood regulation, that encompasses the amygdala, striatum, and ventral PFC. Frontostriatal abnormalities are reported consistently in ADHD, potentially reflecting abnormalities in the development of cognitive control. Children with MDD show prefrontal cortical alterations that may differ in familial and nonfamilial subtypes of MDD. CONCLUSIONS: Results from neuroimaging studies of childhood psychopathology reveal abnormalities in the developmental trajectories observed in healthy children. Although MRI has increased our understanding of the pathophysiology of these disorders, routine neuroimaging for children with severe emotional disturbances is not indicated for diagnostic purposes. 相似文献
85.
Objectives: Previous studies have been inconsistent with regard to the extent to which stress perception, rather than stressor exposure, predicts negative health symptoms. Because sex differences have been observed in all three of these variables, in this study the possibility that sex differences also exist in the relationships between them is investigated. Methods: Self‐report inventories of perceived stress, stressor exposure, and negative health symptoms were given to 107 young‐adult participants (65 females, 42 males). Results: Sex differences were observed in the associations among perceived stress, stressor exposure, and negative health symptom rates. Specifically, while higher perceived stress and higher stressor exposure rates independently predicted higher negative health symptoms rates in females, only higher stressor exposure rates independently predicted higher negative health symptoms in males. Indeed, unexpectedly, after controlling for exposure to stressors there was a trend towards higher perceived stress predicting lower negative health symptoms in males. Conclusions: While exposure to stress was a significant negative predictor of health for both sexes, perception of stress was predictive only for females. One implication of this finding is that different psychological models are needed to predict health symptoms in the two sexes. Copyright © 2005 John Wiley & Sons, Ltd. 相似文献
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Jane Parry 《British medical journal》2003,326(7403):1350
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