Functional role of Calcium-stimulated adenylyl cyclase 8 in adaptations to psychological stressors in the mouse: implications for mood disorders

Razzoli, Maria; Andreoli, Michela; Maraia, G.; Francesco, Carla Di; Arban, Roberto

doi:10.1016/j.neuroscience.2010.07.022

Cited by 21 publications

(18 citation statements)

References 47 publications

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“…Such studies are in accord with reports of mammalian adenylyl cyclase 5 knockout, where restraint stress causes animals to display increased anxiety [17]. Knockouts of mammalian adenylyl cyclase 8, however, actually show a decrease in anxious behavior in response to stress [15], [16], [18]. cAMP may influence neuronal function through activation of HCN channels [47], the EPAC exchange protein [48] and through activation of PKA [49] which phosphorylates downstream effectors such as Synapsin [39].…”

Section: Discussionsupporting

confidence: 83%

“…The role of cAMP signaling in the stress response, however, is unknown. Studies in mammalian models have demonstrated changes in the behavioral response to stress in cAMP pathway mutants [15]–[18]. Similarly, Drosophila studies suggested that cAMP pathway mutants are hypersensitive to aversive stimuli which elicit stress [19], however a direct link to motor function has not been characterized.…”

Section: Introductionmentioning

confidence: 99%

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The Effect of Stress on Motor Function in Drosophila

Chadha

Cook

2014

PLoS ONE

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Exposure to unpredictable and uncontrollable conditions causes animals to perceive stress and change their behavior. It is unclear how the perception of stress modifies the motor components of behavior and which molecular pathways affect the behavioral change. In order to understand how stress affects motor function, we developed an experimental platform that quantifies walking motions in Drosophila. We found that stress induction using electrical shock results in backwards motions of the forelegs at the end of walking strides. These leg retrogressions persisted during repeated stimulation, although they habituated substantially. The motions also continued for several strides after the end of the shock, indicating that stress induces a behavioral aftereffect. Such aftereffect could also be induced by restricting the motion of the flies via wing suspension. Further, the long-term effects could be amplified by combining either immobilization or electric shock with additional stressors. Thus, retrogression is a lingering form of response to a broad range of stressful conditions, which cause the fly to search for a foothold when it faces extreme and unexpected challenges. Mutants in the cAMP signaling pathway enhanced the stress response, indicating that this pathway regulates the behavioral response to stress. Our findings identify the effect of stress on a specific motor component of behavior and define the role of cAMP signaling in this stress response.

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Section: Discussionsupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

The Effect of Stress on Motor Function in Drosophila

Chadha

Cook

2014

PLoS ONE

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“…Ferguson et al demonstrated that Slc5a7 is an essential and regulated presynaptic component of cholinergic signaling and Slc5a7 warrants consideration as a candidate gene for disorders characterized by cholinergic hypofunction [57]. In the CNS, the cholinergic system plays an important role in learning and memory ability, and brain cholinergic dysfunction results in dementia with symptoms such as memory loss and disorientation in cerebrovascular or Alzheimer’s disease [58]. Adenylate cyclase 8 (ADCY8 or AC8) is a pure Ca 2+ sensor, catalyzing the transformation of ATP to cAMP, with an important role in neuronal plasticity.…”

Section: Discussionmentioning

confidence: 99%

Gene-Expression Changes in Cerium Chloride-Induced Injury of Mouse Hippocampus

Cheng

Zhao

et al. 2013

PLoS ONE

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Cerium is widely used in many aspects of modern society, including agriculture, industry and medicine. It has been demonstrated to enter the ecological environment, is then transferred to humans through food chains, and causes toxic actions in several organs including the brain of animals. However, the neurotoxic molecular mechanisms are not clearly understood. In this study, mice were exposed to 0.5, 1, and 2 mg/kg BW cerium chloride (CeCl3) for 90 consecutive days, and their learning and memory ability as well as hippocampal gene expression profile were investigated. Our findings suggested that exposure to CeCl3 led to hippocampal lesions, apoptosis, oxidative stress and impairment of spatial recognition memory. Furthermore, microarray data showed marked alterations in the expression of 154 genes involved in learning and memory, immunity and inflammation, signal transduction, apoptosis and response to stress in the 2 mg/kg CeCl3 exposed hippocampi. Specifically, the significant up-regulation of Axud1, Cdc37, and Ube2v1 caused severe apoptosis, and great suppression of Adcy8, Fos, and Slc5a7 expression led to impairment of mouse cognitive ability. Therefore, Axud1, Cdc37, Ube2v1, Adcy8, Fos, and Slc5a7 may be potential biomarkers of hippocampal toxicity caused by CeCl3 exposure.

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“…AC8 is expressed at high levels in adult brain, and the AC8 knockout shows significant impairment in short-term plasticity and abnormal anxiety behavior under stress (Schaefer et al, 2000;, in addition to the overlapping functions with AC1 discussed above. Lack of AC8 confers a hyperactive phenotype and an increased risk-taking behavior, similar to certain mood disorders (Razzoli et al, 2010). AC8 is also required for glucose homeostasis and hypothalamic adaptation to high-fat diet (Raoux et al, 2015).…”

mentioning

confidence: 99%