Sex-Dependent Behavioral Functions of the Purkinje Cell-Specific Gαi/o Binding Protein, Pcp2(L7)

Walton, James C.; Schilling, Karl; Nelson, Randy J.; Oberdick, John

doi:10.1007/s12311-012-0368-4

Cited by 11 publications

(11 citation statements)

References 72 publications

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“…The three chamber social test was performed using male mice as previously described [29]. Briefly, the test consists of three phases: habituation, sociability, and preference for social novelty [30].…”

Section: Methodsmentioning

confidence: 99%

Neuronal nitric oxide synthase and NADPH oxidase interact to affect cognitive, affective, and social behaviors in mice

Walton

Selvakumar

Weil

et al. 2013

Behavioural Brain Research

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Both nitric oxide (NO) and reactive oxygen species (ROS) generated by nNOS and NADPH oxidase (NOX), respectively, in the brain have been implicated in an array of behaviors ranging from learning and memory to social interactions. Although recent work has elucidated how these separate redox pathways regulate neural function and behavior, the interaction of these two pathways in the regulation of neural function and behavior remains unspecified. Toward this end, the p47phox subunit of NOX, and nNOS were deleted to generate double knockout mice that were used to characterize the behavioral outcomes of concurrent impairment of the NO and ROS pathways in the brain. Mice were tested in a battery of behavioral tasks to evaluate learning and memory, as well as social, affective, and cognitive behaviors. p47phox deletion did not affect depressive-like behavior, whereas nNOS deletion abolished it. Both p47phox and nNOS deletion singly reduced anxiety-like behavior, increased general locomotor activity, impaired spatial learning and memory, and impaired preference for social novelty. Deletion of both genes concurrently had synergistic effects to elevate locomotor activity, impair spatial learning and memory, and disrupt prepulse inhibition of acoustic startle. Although preference for social novelty was impaired in single knockouts, double knockout mice displayed elevated levels of preference for social novelty above that of wild type littermates. These data demonstrate that, depending upon modality, deletion of p47phox and nNOS genes have dissimilar, similar, or additive effects. The current findings provide evidence that the NOX and nNOS redox signaling cascades interact in the brain to affect both cognitive function and social behavior.

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Section: Methodsmentioning

confidence: 99%

Neuronal nitric oxide synthase and NADPH oxidase interact to affect cognitive, affective, and social behaviors in mice

Walton

Selvakumar

Weil

et al. 2013

Behavioural Brain Research

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“…Not mention below are PCP2 and RAP1GAP1. PCP2 is expressed exclusively in cerebellar Purkinje cells and retinal bipolar neurons, where it impacts Gi/o signaling (69). The GoLoco motif in Rap1GAP1 is functional and may regulate the GAP activity of the protein (70).…”

Section: G-protein Regulatory Proteinsmentioning

confidence: 99%

The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity

Kehrl

2016

Biochemical Pharmacology

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Leukocyte chemoattractant receptors are members of the G-protein coupled receptor (GPCR) family. Signaling downstream of these receptors directs the localization, positioning and homeostatic trafficking of leukocytes; as well as their recruitment to, and their retention at, inflammatory sites. Ligand induced changes in the molecular conformation of chemoattractant receptors results in the engagement of heterotrimeric G-proteins, which promotes α subunits to undergo GTP/GDP exchange. This results in the functionally release of βγ subunits from the heterotrimers, thereby activating downstream effector molecules, which initiate leukocyte polarization, gradient sensing, and directional migration. Pertussis toxin ADP ribosylates Gαi subunits and prevents chemoattractant receptors from triggering Gαi nucleotide exchange. The use of pertussis toxin revealed the essential importance of Gαi subunit nucleotide exchange for chemoattractant receptor signaling. More recent studies have identified a range of regulatory mechanisms that target these receptors and their associated heterotrimeric G-proteins, thereby helping to control the magnitude, kinetics, and duration of signaling. A failure in these regulatory pathways can lead to impaired receptor signaling and immunopathology. The analysis of mice with targeted deletions of Gαi isoforms as well as some of these G-protein regulatory proteins is providing insights into their roles in chemoattractant receptor signaling.

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“…2B and C). Pcp2 has been suggested to play a role in Purkinje cell differentiation and Mbp gene regulate oligodendrocyte maturation (Eylar et al 1971, Walton et al 2012. All these genes harbor TREs and are direct targets of TRs in developing cerebellum.…”

Section: Hdac Inhibition Partially Reverses Th-responsive Gene Represmentioning

confidence: 99%

Histone deacetylase inhibition reduces hypothyroidism-induced neurodevelopmental defects in rats

Kumar

Mohan

Sinha

et al. 2015

Journal of Endocrinology

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Thyroid hormone (TH) through its receptor (TRa/b) influences spatio-temporal regulation of its target gene repertoire during brain development. Though hypothyroidism in WT rodent models of perinatal hypothyroidism severely impairs neurodevelopment, its effect on TRa/b knockout mice is less severe. An explanation to this paradox is attributed to a possible repressive action of unliganded TRs during development. Since unliganded TRs suppress gene expression through the recruitment of histone deacetylase (HDACs) via co-repressor complexes, we tested whether pharmacological inhibition of HDACs may prevent the effects of hypothyroidism on brain development. Using valproate, an HDAC inhibitor, we show that HDAC inhibition significantly blocks the deleterious effects of hypothyroidism on rat cerebellum, evident by recovery of TH target genes like Bdnf, Pcp2 and Mbp as well as improved dendritic structure of cerebellar Purkinje neurons. Together with this, HDAC inhibition also rescues hypothyroidism-induced motor and cognitive defects. This study therefore provides an insight into the role of HDACs in TH insufficiency during neurodevelopment and their inhibition as a possible therapeutics for treatment.

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Sex-Dependent Behavioral Functions of the Purkinje Cell-Specific Gαi/o Binding Protein, Pcp2(L7)

Cited by 11 publications

References 72 publications

Neuronal nitric oxide synthase and NADPH oxidase interact to affect cognitive, affective, and social behaviors in mice

Neuronal nitric oxide synthase and NADPH oxidase interact to affect cognitive, affective, and social behaviors in mice

The impact of RGS and other G-protein regulatory proteins on Gαi-mediated signaling in immunity

Histone deacetylase inhibition reduces hypothyroidism-induced neurodevelopmental defects in rats

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