Altered Stress-Induced Anxiety in Adenylyl Cyclase Type VIII-Deficient Mice

Schaefer, Michele L.; Wong, Scott T.; Wozniak, David F.; Muglia, Lisa M.; Liauw, Jason; Zhuo, Min; Nardi, A.; Hartman, Richard E.; Vogt, Sherri K.; Luedke, Christina; Storm, Daniel R.; Muglia, Louis J.

doi:10.1523/jneurosci.20-13-04809.2000

Cited by 146 publications

(120 citation statements)

References 59 publications

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“…4b) between FBGRKO and control mice in this test (n ϭ 10). The similar activity between control and FBGRKO mice in this open-field measure is consistent with our previous analysis of general locomotor activity under basal conditions using beam breaks in a photocell apparatus (Schaefer et al, 2000;Boyle et al, 2005). Thus, the FBGRKO mice are not hyperactive in general.…”

Section: Locomotor Activation In the Elevated Plus Mazesupporting

confidence: 90%

Forebrain Glucocorticoid Receptors Modulate Anxiety-Associated Locomotor Activation and Adrenal Responsiveness

Boyle¹,

Kolber²,

Vogt³

et al. 2006

J. Neurosci.

151

115

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Stress potently modulates anxiety-and depression-related behaviors. In response to stressors, the hypothalamic-pituitary-adrenal (HPA) axis is activated, resulting in the release of glucocorticoids from the adrenal cortex. These hormones act peripherally to restore homeostasis but also feed back to the CNS to control the intensity and duration of the stress response. Glucocorticoids act in limbic areas of the CNS to mediate the psychological and behavioral effects of stress. In this study, we investigate the effect of forebrain-specific disruption of the glucocorticoid receptor (GR) on stress-and anxiety-related behaviors. We demonstrate that mice with disruption of forebrain GR show alterations in stress-induced locomotor activation in a number of anxiety-related behavioral paradigms. These changes are associated with alterations in stress-induced HPA axis activation and, importantly, are not attenuated by chronic treatment with the tricyclic antidepressant imipramine. These data demonstrate the importance of forebrain GR in regulation of physiological and behavioral stress reactivity and suggest that distinct pathways regulate despair-and anxiety-related behaviors.

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Section: Locomotor Activation In the Elevated Plus Mazesupporting

confidence: 90%

Forebrain Glucocorticoid Receptors Modulate Anxiety-Associated Locomotor Activation and Adrenal Responsiveness

Boyle¹,

Kolber²,

Vogt³

et al. 2006

J. Neurosci.

151

115

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“…It has been shown that expression of specific isoforms, subcellular localization, and differential regulation of ACs greatly contribute to the diverse and tissue-specific regulation of cAMP (33)(34)(35)(36)(37). Here we report a novel regulatory pathway for control of cAMP synthesis in three hematopoietic cell lines.…”

Section: Discussionmentioning

confidence: 90%

Regulation of cAMP Responses by the G12/13 Pathway Converges on Adenylyl Cyclase VII

Jiang

Collins

Davis

et al. 2008

Journal of Biological Chemistry

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Regulation of intracellular cAMP by multiple pathways enables differential function of this ubiquitous second messenger in a context-dependent manner. Modulation of G s -stimulated intracellular cAMP has long been known to be modulated by the G i and G q /Ca 2؉ pathways. Recently, the G 13 pathway was also shown to facilitate cAMP responses in murine macrophage cells. We report here that this synergistic regulation of cAMP synthesis by the G s and G 13 pathways is mediated by a specific isoform of adenylyl cyclase, AC7. Furthermore, this signaling paradigm exists in several hematopoietic lineages and can be recapitulated by exogenous expression of AC7 in HEK 293 cells. Mechanistic characterization of this synergistic interaction indicates that it occurs downstream of receptor activation and it can be mediated by the ␣ subunit of either G 12 or G 13 . Our results demonstrate that AC7 is a specific downstream effector of the G 12/13 pathway.

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“…Although mice deficient in either mAC VIII or G␣ olf are fertile but rarely surviving (43,44), homozygous matings of mAC III K.O. mice were unproductive, although they showed normal mounting and anogenital sniffing behaviors (45).…”

Section: Discussionmentioning

confidence: 99%

Particulate Adenylate Cyclase Plays a Key Role in Human Sperm Olfactory Receptor-mediated Chemotaxis

Spehr

Schwane

Riffell

et al. 2004

Journal of Biological Chemistry

142

131

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Human sperm chemotaxis is a critical component of the fertilization process, but the molecular basis for this behavior remains unclear. Recent evidence shows that chemotactic responses depend on activation of the sperm olfactory receptor, hOR17-4. Certain floral scents, including bourgeonal, activate hOR17-4, trigger pronounced Ca 2؉ fluxes, and evoke chemotaxis. Here, we provide evidence that hOR17-4 activation is coupled to a cAMP-mediated signaling cascade. Multidimensional protein identification technology was used to identify potential components of a G-protein-coupled cAMP transduction pathway in human sperm. These products included various membrane-associated adenylate cyclase (mAC) isoforms and the G olf -subunit. Using immunocytochemistry, specific mAC isoforms were localized to particular cell regions. Whereas mAC III occurred in the sperm head and midpiece, mAC VIII was distributed predominantly in the flagellum. In contrast, G olf was found mostly in the flagellum and midpiece. The observed spatial distribution patterns largely correspond to the spatiotemporal character of hOR17-4-induced Ca 2؉ changes. Behavioral and Ca 2؉ signaling responses of human sperm to bourgeonal were bioassayed in the presence, or absence, of the adenylate cyclase antagonist SQ22536. This specific agent inhibits particulate AC, but not soluble AC, activation. Upon incubation with SQ22536, cells ceased to exhibit Ca 2؉ signaling, chemotaxis, and hyperactivation (faster swim speed and flagellar beat rate) in response to bourgeonal. Particulate AC is therefore required for induction of hOR17-4-mediated human sperm behavior and represents a promising target for future design of contraceptive drugs.

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Altered Stress-Induced Anxiety in Adenylyl Cyclase Type VIII-Deficient Mice

Cited by 146 publications

References 59 publications

Forebrain Glucocorticoid Receptors Modulate Anxiety-Associated Locomotor Activation and Adrenal Responsiveness

Forebrain Glucocorticoid Receptors Modulate Anxiety-Associated Locomotor Activation and Adrenal Responsiveness

Regulation of cAMP Responses by the G12/13 Pathway Converges on Adenylyl Cyclase VII

Particulate Adenylate Cyclase Plays a Key Role in Human Sperm Olfactory Receptor-mediated Chemotaxis

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