Region-Specific Disruption of Adenylate Cyclase Type 1 Gene Differentially Affects Somatosensorimotor Behaviors in Mice

Arakawa, Hiroyuki; Akkentli, Fatih; Erzurumlu, Reha S.

doi:10.1523/eneuro.0007-14.2014

Cited by 14 publications

(11 citation statements)

References 34 publications

(65 reference statements)

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“…Similarly, statistically equivalent reductions in average ambulations across repeated saline acclimation sessions (data not shown) were observed within WT versus AC1KO [two-way RM ANOVA significant effect of time: F(2,50) = 43.64, P < 0.001; no genotype effect: F(1,25) = 0.344, P = 0.563; or interaction: F(2,50) = 2.760, P = 0.073] and WT saline versus WT NB001 groups [two-way RM ANOVA significant effect of time: F(3,99) = 23.99, P < 0.001; no treatment effect: F(1,33) = 3.418, P = 0.0735; or interaction: F(3,99) = 1.876, P = 0.1386]. These data indicate the absence of AC1 does not influence the locomotor response to novelty or induce general motor impairments, consistent with observations following global AC1 gene deficiency ( Arakawa et al, 2014 ) and NB001 treatment ( Wang et al, 2011 ).…”

Section: Resultssupporting

confidence: 84%

Adenylyl Cyclase 1 Is Required for Ethanol-Induced Locomotor Sensitization and Associated Increases in NMDA Receptor Phosphorylation and Function in the Dorsal Medial Striatum

Bosse

Oginsky

Susick

et al. 2017

J Pharmacol Exp Ther

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Neuroadaptive responses to chronic ethanol, such as behavioral sensitization, are associated with N-methyl-D-aspartate receptor (NMDAR) recruitment. Ethanol enhances GluN2B-containing NMDAR function and phosphorylation (Tyr-1472) of the GluN2B-NMDAR subunit in the dorsal medial striatum (DMS) through a protein kinase A (PKA)–dependent pathway. Ethanol-induced phosphorylation of PKA substrates is partially mediated by calcium-stimulated adenylyl cyclase 1 (AC1), which is enriched in the dorsal striatum. As such, AC1 is poised as an upstream modulator of ethanol-induced DMS neuroadaptations that promote drug responding, and thus represents a therapeutic target. Our hypothesis is that loss of AC1 activity will prevent ethanol-induced locomotor sensitization and associated DMS GluN2B-NMDAR adaptations. We evaluated AC1’s contribution to ethanol-evoked locomotor responses and DMS GluN2B-NMDAR phosphorylation and function using AC1 knockout (AC1KO) mice. Results were mechanistically validated with the AC1 inhibitor, NB001. Acute ethanol (2.0 g/kg) locomotor responses in AC1KO and wild-type (WT) mice pretreated with NB001 (10 mg/kg) were comparable to WT ethanol controls. However, repeated ethanol treatment (10 days, 2.5 g/kg) failed to produce sensitization in AC1KO or NB001 pretreated mice, as observed in WT ethanol controls, following challenge exposure (2.0 g/kg). Repeated exposure to ethanol in the sensitization procedure significantly increased pTyr-1472 GluN2B levels and GluN2B-containing NMDAR transmission in the DMS of WT mice. Loss of AC1 signaling impaired ethanol-induced increases in DMS pGluN2B levels and NMDAR-mediated transmission. Together, these data support a critical and specific role for AC1 in striatal signaling that mediates ethanol-induced behavioral sensitization, and identify GluN2B-containing NMDARs as an important AC1 target.

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Section: Resultssupporting

confidence: 84%

Adenylyl Cyclase 1 Is Required for Ethanol-Induced Locomotor Sensitization and Associated Increases in NMDA Receptor Phosphorylation and Function in the Dorsal Medial Striatum

Bosse

Oginsky

Susick

et al. 2017

J Pharmacol Exp Ther

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“…Pups were housed with their dams but they needed to search and find solid food by themselves as the onset of self-feeding. Whisker clipped mice clearly showed a decreased investigation in the open arena and toward placed objects and significant impairment in texture/shape recognition [22,63]. It is highly possible that the deafferentation of whiskers induces delayed transition to solid food or impairment in solid food feeding.…”

Section: Discussionmentioning

confidence: 99%

“…The battery of tests we chose is also important in assessing whisker sensation-related deficits in ever increasing numbers of genetically altered mouse lines, in which various aspects of whisker-related neural patterns and function in the brain are altered. For example, adenylate cyclase type 1 gene deficient mice, which are known as barreless mice, reveal significant impairment in tactile sensation as well as body coordination in various behavioral tests [63]. …”

Section: Introductionmentioning

confidence: 99%

Role of whiskers in sensorimotor development of C57BL/6 mice

Arakawa

Erzurumlu

2015

Behavioural Brain Research

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The mystacial vibrissae (whiskers) of nocturnal rodents play a major role in their sensorimotor behaviors. Relatively little information exists on the role of whiskers during early development. We characterized the contribution of whiskers to sensorimotor development in postnatal C57BL/6 mice. A comparison between intact and whisker-clipped mice in a battery of behavioral tests from postnatal day (P) 4 to 17 revealed that both male and female pups develop reflexive motor behavior even when the whiskers are clipped. Daily whisker trimming from P3 onwards results in diminished weight gain by P17, and impairment in whisker sensorimotor coordination behaviors, such as cliff avoidance and littermate huddling from P4 through P17, while facilitation of righting reflex at P4 and grasp response at P12. Since active whisker palpation does not start until 2 weeks of age, passive whisker touch during early neonatal stage must play a role in regulating these behaviors. Around the onset of exploratory behaviors (P12) neonatal whisker-clipped pups also display persistent searching movements when they encounter cage walls as a compensatory mechanism of sensorimotor development. Spontaneous whisker motion (whisking) is distinct from respiratory fluttering of whiskers. It is a symmetrical vibration of whiskers at a rate of approximately ∼8 Hz, and begins around P10. Oriented, bundled movements of whiskers at higher frequencies of ∼12 Hz during scanning object surfaces, i.e., palpation whisking, emerges at P14. The establishment of locomotive body coordination before eyes open accompanies palpation whisking, indicating an important role in the guidance of exploratory motor behaviors.

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“…It could also affect hearing function in human and zebrafish 20. ADCY1 was a main regulator of the cAMP signaling pathway 21. It was also discovered to participate in a dopamine D4 receptors (D4Rs) modulated signaling pathway activated by neuronal PAS-domain protein 2 (NPAS2), which can regulate the circadian sensitivity of retinal ganglion cells 22.…”

Section: Introductionmentioning

confidence: 99%

“…It was also discovered to participate in a dopamine D4 receptors (D4Rs) modulated signaling pathway activated by neuronal PAS-domain protein 2 (NPAS2), which can regulate the circadian sensitivity of retinal ganglion cells 22. Loss of ADCY1 function might lead to drastically-behavioral impairments in sensorimotor and social behaviors 23. ADCY1 was also reported to be associated with alcohol addiction, and depression from adolescence to adult as well as in postpartum motherhood, which were accompanied by a down-regulation of ADCY1 expression 24, 25.…”

Section: Introductionmentioning

confidence: 99%

A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer

et al. 2019

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Adenylate cyclase 1 (ADCY1 or AC1) is a member of ADCY superfamily and was primarily found to be expressed in the brain. ADCY1 is responsible for catalyzing ATP to cyclic AMP (cAMP). As a secondary messenger, cAMP can regulate plenty of cellular activities. cAMP can perform its regulation in cellular transport through the binding to cAMP dependent protein kinases (PKAs), cAMP-activated guanine exchange factors (EPACs) and cyclic nucleotide-gated channels functioning in transduction of sensory signals (CNGs). Lung cancer is one of the leading factors of cancer-related death worldwide. Platinum-based chemotherapy is the first-line treatment for advanced lung cancer patients. In addition, surgical treatment, radiation treatment, and molecular targeted therapy are also therapeutic options for lung cancer patients in clinical settings. However, drug resistance and toxicity are the major obstacles that affect chemotherapy outcome and prognosis of lung cancer patients. And the therapeutic efficiency and adverse effects are varying with each individual. In recent years, investigations based on genetic sequencing have revealed the emerging role of ADCY1 mutations in affecting drug efficiency in various cancers such as lung cancer, esophageal cancer and colorectal cancer. The potential function of ADCY1 in chemotherapy resistance is of great importance to be noticed and investigated.

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Region-Specific Disruption of Adenylate Cyclase Type 1 Gene Differentially Affects Somatosensorimotor Behaviors in Mice

Abstract: The neuron-specific calcium-stimulated adenylate cyclase 1 (AC1) is important for refinement of topographic maps in the brain. AC1 is expressed at all levels of the somatosensory pathway and global or region-specific gene deletions lead to differential pattern phenotypes.

Cited by 14 publications

References 34 publications

Adenylyl Cyclase 1 Is Required for Ethanol-Induced Locomotor Sensitization and Associated Increases in NMDA Receptor Phosphorylation and Function in the Dorsal Medial Striatum

Adenylyl Cyclase 1 Is Required for Ethanol-Induced Locomotor Sensitization and Associated Increases in NMDA Receptor Phosphorylation and Function in the Dorsal Medial Striatum

Role of whiskers in sensorimotor development of C57BL/6 mice

A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer

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