A3 Mania Auto Clicker 29
Excessive motivation, such as increased reward-seeking behavior or drive to perform or to achieve goals, is common during mania (35). To assess preference for a natural reward, we tested sucrose preference. We found that Myk/+ mice consumed more sucrose solution relative to water than +/+ mice (Fig. 3C). In addition, Myk/+ mice initially consumed more sucrose solution before the choice test (Fig. 3D). The increased preference for sucrose is indicative of a hyperhedonic state common to mania. To assess drive and motivation, we used the Porsolt forced swim test, which involves measurement of escape-directed behavior. In this test, Myk/+ mice spent a longer time active than +/+ mice (Fig. 3E). Antidepressant drugs have been shown to increase the duration of mobility in the forced swim test (36) and the increased escape-directed behavior of Myk/+ mice suggests a lower level of depressive-like behavior, which correlates with their increase in preference for rewarding stimuli.
a3 mania auto clicker 29
Attenuation of mania-like behavior by lithium and VPA in Myk/+ mice. (A) Chronic treatment with lithium reduces total distance traveled by Myk/+ (n = 20) compared to untreated Myk/+ (n = 22) over 30 min in the open field and had no effect in +/+ mice (n = 28 control, n = 27 lithium). (B) VPA reduced total distance traveled by Myk/+ (n = 20) compared to vehicle-treated Myk/+ (n = 22), and had no effect on +/+ mice (n = 28 vehicle, n = 27 VPA) over 30 min. (C) Lithium reduces open-arm duration in Myk/+ (n = 18) compared with control Myk/+ (n = 19), but had no effect on +/+ mice (n = 29 control, n = 29 lithium) in the EPM. (D) VPA reduces open-arm duration in Myk/+ (n = 12) compared with vehicle-treated Myk/+ (n = 10) but had no effect on +/+ mice (n = 12 control, n = 12 VPA) in the EPM. (E) ERK inhibitor SL327 decreased distance traveled in Myk/+ (n = 12) compared with vehicle-treated Myk/+ (n = 9), and had no effect in +/+ mice (n = 12 vehicle, n = 12 SL327) in the open field. (F) SL327 reduced open-arm duration in Myk/+ (n = 6) compared with Myk/+ vehicle (n = 6) but had no effect on +/+ mice (n = 6 control, n = 6 SL327) in the EPM. (G) Rostafuroxin decreased distance traveled in Myk/+ (n = 12) compared with vehicle treatment (n = 12) and had no effect in +/+ mice (n = 13 vehicle, n = 15 rostafuroxin) in the open field. (H) In the EPM rostafuroxin reduced open arm duration in Myk/+ (n = 12) compared with vehicle treated Myk/+ (n = 12) and had no effect in +/+ mice (n = 12 vehicle, n = 15 rostafuroxin). All data are presented as means SEM, *P
Free intracellular Ca2+ and Ca2+-dependent signaling in Myk/+ mice. (A) Mean resting intracellular ([Ca2+]i) is stably elevated in cortical cells cultured from Myk/+ (n = 47) than +/+ mice (n = 19), as measured by the ratio of fura-2 fluorescence emission upon 340-nm and 380-nm excitation (P
Increasing the contribution of the seizure-resistant C57BL/6NCr strain (23) to the genetic background of Myk/+ mice had a significant phenotypic impact. In contrast to N12 C57BL/6NCr Myk/+ mice, Myk/+ mice at N20 C57BL/6NCr did not show stress-induced seizure activity in ECoG recordings and had increased total brain NKA activity. These results support our previous finding that an increase in NKA activity contributes to seizure resistance (21). Nonetheless, the possibility remains that unobserved subcortical epileptiform discharges contribute to mania-like behavior in Myk/+ mice. Interestingly, epilepsy and bipolar disorder can be comorbid in humans (48) and they share a common pathophysiology (49). Given that Myk/+ mice and ICV ouabain-treated rats exhibit mania-like behavior and increased susceptibility to seizures (50, 51), these models may help to explain why these debilitating conditions can be comorbid and suggest that increasing NKA activity may serve as therapy for mania and epilepsy.
Thus far, there have been no indications that Myk/+ mice cycle between mania and depression, and future studies may determine whether depression-like symptoms occur after stress, sleep deprivation, or administration of antidepressants. However, we have shown that mice heterozygous for a point mutation in Atp1a3 intron 4 (Atp1a3tm1Ling) exhibit increased susceptibility to depression-related behavior and a 33% reduction of brain NKA activity following chronic variable stress (52). Taking these data together, our work suggests that mood is significantly correlated with reductions in brain NKA activity. Theoretically, as previously hypothesized (53, 54), modulation of NKA activity could account for changes in mood in bipolar disorder.
Similar to an ouabain model of mania (8), phospho-activation of the ERK signaling cascade was enhanced in Myk/+ hippocampus, possibly by increasing transmitter-evoked Ca2+ signaling. However, p-ERK levels were not restored in Myk/+/Tg mice, suggesting that multiple signals contribute to mania-like behavior. In parallel with previous findings (42), the dose of SL327 that we used had no effect on locomotor activity in +/+ mice. In contrast, a higher dose of SL327 (60) or deletion of the Mapk3 (ERK1) gene (44, 61) have been shown to increase locomotor activity in rats and mice, respectively. These results suggest that the degree of ERK activation is correlated with mania-like behavior in animal models, and support the ERK pathway as a promising target for mood stabilizers (62). Also in accordance with an ouabain model of mania (9), the Myk/+ hippocampus showed elevated phospho-activation of Akt. p-Akt was reduced in Myk/+/Tg mice, suggesting it may contribute to the regulation of mania-like behavior. Activated Akt phosphorylates and inhibits the activity of GSK-3β, a well-known molecular target of lithium and VPA (63), mood stabilizing drugs that diminished many of the behavioral abnormalities of Myk/+ mice. Because Akt/GSK-3β signaling is regulated by dopamine (64), our results suggest that Akt may also be a promising target for mood stabilizers. Myk/+ mice could be used as a tool to investigate the potential of ERK and Akt modulators as antimanic therapies and to assess the prophylactic effect of novel mood stabilizers. Finally, because Myk/+ mice and ouabain-treated rats show similar p-ERK and p-Akt increases in the hippocampus, the genetic Myk/+ model of mania may replace the pharmacological ouabain model of mania, thus providing a less laborious model for exploring potential therapeutic approaches.
Rostafuroxin is a digitoxigenin derivative that antagonizes the signaling action of endogenous ouabain on the NKA that acts upstream of ERK to reduce ouabain-mediated NKA signaling (43). Its effective reduction of mania-like behavior in Myk/+ mice supports the notion that the phenotype of Myk/+ mice is caused by increased NKA downstream signaling.
On this West Virginia Morning, book deserts are places without nearby libraries or bookstores, which can be very hard for children just learning to read. Morgantown High School senior Rania Zuri is trying to fight that and bring books to kids in West Virginia. Inside Appalachia\u2019s Mason Adams spoke with her.\n\n\n\nAlso, in this show, a number of health-related issues have been on the table this legislative session \u2014 from gender-affirming care, to PEIA coverage and even foster care splitting up DHHR. For our Friday reporter roundtable on The Legislature Today, Chris Schulz spoke with WVPB\u2019s Appalachia Health News Reporter Emily Rice and Allen Siegler from Mountain State Spotlight.\n\n\n\nWest Virginia Morning is a production of West Virginia Public Broadcasting which is solely responsible for its content.\n\n\n\nSupport for our news bureaus comes from West Virginia University, Concord University, and Shepherd University.\n\n\n\nListen to West Virginia Morning weekdays at 7:43 a.m. on WVPB Radio or subscribe to the podcast and never miss an episode. #WVMorning\n","post_title":"Health Legislation And Ending Book Deserts On This West Virginia Morning","post_excerpt":"On this West Virginia Morning, book deserts are places without nearby libraries or bookstores, which can be very hard for children just learning to read. Morgantown High School senior Rania Zuri is trying to fight that and bring books to kids in West Virginia. Inside Appalachia\u2019s Mason Adams spoke with her.","post_status":"publish","comment_status":"closed","ping_status":"closed","post_password":"","post_name":"health-legislation-and-ending-book-deserts-on-this-west-virginia-morning","to_ping":"","pinged":"","post_modified":"2023-02-06 10:35:20","post_modified_gmt":"2023-02-06 15:35:20","post_content_filtered":"","post_parent":0,"guid":"https:\/\/wvpublic.org\/?p=28532","menu_order":0,"post_type":"post","post_mime_type":"","comment_count":"0","filter":"raw","m":"_edit_lock":["1675697721:15"],"_thumbnail_id":["28533"],"_edit_last":["15"],"hide_title":["0"],"_hide_title":["field_6362790886020"],"mp3":["28534"],"_mp3":["field_63a1b52bcc11c"],"mp3_url":[""],"_mp3_url":["field_63cae2d50401f"],"additional_authors":[""],"_additional_authors":["field_63cffa54ad502"],"_yoast_wpseo_primary_category":["59"],"_yoast_wpseo_content_score":["90"],"_yoast_wpseo_estimated-reading-time-minutes":["1"],"_yoast_wpseo_wordproof_timestamp":[""],"link":"https:\/\/wvpublic.org\/health-legislation-and-ending-book-deserts-on-this-west-virginia-morning\/","sticky":false,"relative_time":"About 19 hours ago","cats":["term_id":59,"name":"Arts & Culture","slug":"arts-culture","term_group":0,"term_taxonomy_id":59,"taxonomy":"category","description":"Arts & Culture stories","parent":0,"count":529,"filter":"raw","cat_ID":59,"category_count":529,"category_description":"Arts & Culture stories","cat_name":"Arts & Culture","category_nicename":"arts-culture","category_parent":0],"tags":["term_id":15370,"name":"Book Deserts","slug":"book-deserts","term_group":0,"term_taxonomy_id":15370,"taxonomy":"post_tag","description":"","parent":0,"count":3,"filter":"raw","term_id":74,"name":"Government","slug":"government","term_group":0,"term_taxonomy_id":74,"taxonomy":"post_tag","description":"","parent":0,"count":6449,"filter":"raw","term_id":430,"name":"Health","slug":"health","term_group":0,"term_taxonomy_id":430,"taxonomy":"post_tag","description":"","parent":0,"count":106,"filter":"raw","term_id":1966,"name":"podcast","slug":"podcast","term_group":0,"term_taxonomy_id":1966,"taxonomy":"post_tag","description":"","parent":0,"count":2637,"filter":"raw","term_id":14194,"name":"Podcast - West Virginia Morning","slug":"podcast-west-virginia-morning","term_group":0,"term_taxonomy_id":14194,"taxonomy":"post_tag","description":"Local news stories from West Virginia Public Broadcasting. Whether it's important news events, interesting features about people and places, the latest in environmental news, stories about education or the economy, West Virginia Public Broadcasting's team of experienced reporters bring listeners in depth stories and interviews from around the state.","parent":0,"count":1810,"filter":"raw","term_id":237,"name":"West Virginia Legislature","slug":"west-virginia-legislature","term_group":0,"term_taxonomy_id":237,"taxonomy":"post_tag","description":"","parent":0,"count":564,"filter":"raw"],"author":"data":"ID":"476","user_login":"wvpb-staff","user_pass":"$P$BozehNfezfeaQy3Omf9cZ0ZLjA.rKa.","user_nicename":"wvpb-staff","user_email":"","user_url":"https:\/\/www.wvpublic.org\/wvpb-staff-1","user_registered":"2023-01-06 00:33:53","user_activation_key":"","user_status":"0","display_name":"WVPB 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& Culture","cat_link":"\/category\/arts-culture"},"ID":28535,"post_author":"472","post_date":"2023-02-06 12:05:23","post_date_gmt":"2023-02-06 17:05:23","post_content":"\nMarshall University is hosting a roundtable Monday to explore the idea of Advanced Air Mobility, or drones, for transportation purposes.\n\n\n\nAdvanced Air Mobility (AAM) is the use of unmanned aircraft to transport people and equipment to urban and rural locations not accessible by traditional airplanes. \n\n\n\nAircraft can range in size from small cargo-carrying drones to passenger-carrying air taxis.\n\n\n\nAAM is considered a big opportunity for Appalachia. \n\n\n\nIn the 1950s and 1960s, Appalachian communities became increasingly isolated with an interstate highway system that underserved the area. While reconnecting Appalachian communities has since improved, the region remains largely depressed in the transportation industry, in part due to its challenging terrain.\n\n\n\nBut despite its challenging geography and low population densities, West Virginia is well positioned for multi-modal transportation concepts.\n\n\n\nVertx Partners is helping organize the roundtable event by identifying stakeholders in the Appalachian area - an economy considered dependent on the efficient transportation of goods, people, and sensors.\n\n\n\nThe roundtable is called the Autonomous Aerial Cargo Operations at Scale CONOPS. It is a NASA University Initiative organized by University of Texas - Austin and MIT Lincoln Laboratory in Massachusetts.\n\n\n\nRoundtable
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