Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cε

Hodge, Clyde W.; Raber, Jacob; McMahon, Thomas; Walter, Mboto Helen; Sánchez-Pérez, Ana; Olive, M. Foster; Mehmert, Kristin K.; Morrow, A. Leslie; Messing, Robert O.

doi:10.1172/jci200215903

Cited by 119 publications

(82 citation statements)

References 33 publications

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“…Mice were first tested for spontaneous locomotor activity and anxiety-like behavior (thigmotaxy) in brightly lit (500 lux) chambers (28 cm Â 28 cm) during 15 min sessions as described (Hodge et al, 2002). For assessment of activity in the center of the field, the chamber floor was divided post hoc into a center zone (14 Â 14 cm; center equidistant from all four walls of the chamber) and a periphery zone (the remaining area of the floor).…”

Section: Behavioral Testingmentioning

confidence: 99%

Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice

Stevenson

Schroeder

Nixon

et al. 2008

Neuropsychopharmacol

131

102

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Alcoholism and depression show high degrees of comorbidity. Clinical evidence also indicates that depression that emerges during abstinence from chronic alcohol use has a greater negative impact on relapse than pre-existing depression. Although no single neurobiological mechanism can account for the behavioral pathologies associated with these devastating disorders, converging evidence suggests that aspects of both alcoholism and depression are linked to reductions in hippocampal neurogenesis. Here, we report results from a novel preclinical behavioral model showing that abstinence from voluntary alcohol drinking leads to the emergence of depressionlike behavior and reductions in neurogenesis. C57BL/6J mice were allowed to self-administer ethanol (10% v/v) vs H 2 O in the home cage for 28 days. Alcohol was then removed for 1 or 14 days, and mice were tested in the forced swim test to measure depression-like behavior. After 14 days, but not 1 day of abstinence from alcohol drinking, mice showed a significant increase in depression-like behavior. The significant increase in depression-like behavior during abstinence was associated with a reduction in proliferating cell nuclear antigen (PCNA) and doublecortin (DCX) immunoreactivity in the dentate gyrus of the hippocampus indicating that both the number of proliferating neural progenitor cells (NPC) and immature neurons were reduced, respectively. The number of NPCs that were labeled with bromo-deoxyuridine (BrdU) at the beginning of alcohol exposure was not altered indicating that survival of NPCs is not linked to abstinence-induced depression. Chronic treatment (14 days) with the antidepressant desipramine during abstinence prevented both the emergence of depression-like behavior and the reduction in hippocampal neurogenesis indicating that abstinence-induced depression is associated with structural plasticity in the hippocampus. Overall, the results of this study support the conclusion that profound functional (ie behavioral) and structural changes occur during abstinence from alcohol use and suggest that antidepressant treatment may alleviate some of these pathological neurobehavioral adaptations.

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Section: Behavioral Testingmentioning

confidence: 99%

Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice

Stevenson

Schroeder

Nixon

et al. 2008

Neuropsychopharmacol

131

102

View full text Add to dashboard Cite

show abstract

“…In glutamatergic neurons that express both 5α reductase and 3α HSD and that presumably synthesize allopregnanolone, the data suggest that allopregnanolone probably works in a paracrine fashion at GABA A receptors located on dendrites or cell bodies of those glutamatergic neurons, with or without secretion into the extracellular space, through plasma membrane lateral diffusion or through intracellular routes (Akk et al, 2005). Neurosteroid modulation of GABA-mediated currents involves G-protein and protein kinase activation Fancsik et al, 2000;Harney et al, 2003;Hodge et al, 2002;Vicini et al, 2002;Wegner et al, 2006). Both protein kinase C (epsilon isoform) and protein kinase A have been suggested as being involved in neurosteroid action.…”

Section: General Overviewmentioning

confidence: 99%

Neurosteroid regulation of central nervous system development

Mellon

2007

Pharmacology & Therapeutics

186

117

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Neurosteroids are a relatively new class of neuroactive compounds, brought to prominence in the past two decades. Despite knowing of their presence in the nervous system of various species for over twenty years and knowing of their functions as GABA A and NMDA ligands, new and unexpected functions of these compounds are continuously being identified. Absence or reduced concentrations of neurosteroids during development and in adults may be associated with neurodevelopmental, psychiatric, or behavioral disorders. Treatment with physiologic or pharmacologic concentrations of these compounds may also promote neurogenesis, neuronal survival, myelination, increased memory, and reduced neurotoxicity. This review highlights what is currently known about the neurodevelopmental functions and mechanisms of action of four distinct neurosteroids -pregnenolone, progesterone, allopregnanolone and dehydroepiandrosterone.

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“…A variety of tissues, such as those of the nervous, cardiac, and immune systems, express PKC⑀, and the role of PKC⑀ is important for their proper function (19 -22). PKC⑀ may be a useful therapeutic target to treat disease conditions, such as inflammation (19), ischemia (23), addiction (24), pain (25), anxiety (26,27), and cancer (28,29).…”

mentioning

confidence: 99%

Intracellular Interaction of Interleukin (IL)-32α with Protein Kinase Cϵ (PKCϵ) and STAT3 Protein Augments IL-6 Production in THP-1 Promonocytic Cells

Kang

Park

Lee

et al. 2012

Journal of Biological Chemistry

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Background: IL-32␣ is known to interact with FAK1, and IL-32␣ overexpression in chronic myeloid leukemia cells increases natural killer cell-mediated killing. Results: IL-32␣ interacted with PKC⑀ and STAT3, mediated STAT3 phosphorylation, and thereby augmented IL-6 production. Conclusion: IL-32␣ elevated IL-6 production through interaction with PKC⑀ and STAT3. Significance: The interaction of IL-32␣ with PKC⑀ and STAT3 reveals a new intracellular mediatory role of IL-32␣.

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Decreased anxiety-like behavior, reduced stress hormones, and neurosteroid supersensitivity in mice lacking protein kinase Cε

Cited by 119 publications

References 33 publications

Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice

Abstinence following Alcohol Drinking Produces Depression-Like Behavior and Reduced Hippocampal Neurogenesis in Mice

Neurosteroid regulation of central nervous system development

Intracellular Interaction of Interleukin (IL)-32α with Protein Kinase Cϵ (PKCϵ) and STAT3 Protein Augments IL-6 Production in THP-1 Promonocytic Cells

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