{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T07:02:54Z","timestamp":1772434974242,"version":"3.50.1"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T00:00:00Z","timestamp":1772409600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:p>\n                    Episodic ataxia type 2 (EA2) is caused by loss-of-function mutations in CACNA1A, resulting in P\/Q-type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel dysfunction in cerebellar Purkinje cells (PCs) causing ataxia and stress-induced dystonia. Using Cacna1a\n                    <jats:sup>purk(\u2212\/\u2212)<\/jats:sup>\n                    (\n                    <jats:italic>purky<\/jats:italic>\n                    ) mice, which display selective P\/Q-type channels deletion in PCs, the effects of adrenergic receptor (AR) blockade on stress-induced dystonia were examined. Systemic administration of the \u03b11-AR antagonist prazosin increased dystonia frequency, but shortened attack duration, while the \u03b11D-AR selective antagonist BMY-7378 significantly reduced dystonia occurrence without altering onset or duration. Strikingly, universal blockade of \u03b12-ARs using yohimbine, as well as agonist of \u03b12A-AR autoreceptors completely abolished stress-induced dystonia. Electrophysiological recordings of cerebellar PCs demonstrated that norepinephrine (NE) strongly inhibited the PC simple spike firing, which was partially rescued by yohimbine, implicating \u03b12-AR\u2013dependent modulation of PC activity. Histological analysis of\n                    <jats:italic>purky<\/jats:italic>\n                    mice revealed increased dopamine-\n                    <jats:italic>\u03b2<\/jats:italic>\n                    -hydroxylase (D\u03b2H) immunoreactivity on PC somata, which was accompanied by increased numbers of noradrenergic neurons in locus coeruleus (LC), indicating enhanced cerebellar noradrenergic innervation. These findings strengthen the idea that stress-induced dystonia formation is facilitated by increased noradrenergic innervation to cerebellar PCs and suggest that \u03b12-AR signalling contributes to dystonia in EA2. Our findings emphasise cerebellar ARs as promising therapeutic targets in EA2.\n                  <\/jats:p>","DOI":"10.3389\/fnins.2026.1765171","type":"journal-article","created":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T06:32:49Z","timestamp":1772433169000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Adrenergic receptor activation triggers stress-induced dystonia in a CACNA1A mutant mouse model"],"prefix":"10.3389","volume":"20","author":[{"given":"Pauline","family":"Bohne","sequence":"first","affiliation":[{"name":"Department of Behavioral Neuroscience, Ruhr-University Bochum","place":["Bochum, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle","family":"Gr\u00f6mmke","sequence":"additional","affiliation":[{"name":"Department of Zoology and Neurobiology, Ruhr-University Bochum","place":["Bochum, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Max","family":"Rybarski","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Ruhr-University Bochum","place":["Bochum, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tejas","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Ruhr-University Bochum","place":["Bochum, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melanie D.","family":"Mark","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Ruhr-University Bochum","place":["Bochum, Germany"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,2]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1002\/1526-968X(200011\/12)28:3\/4<93::AID-GENE10>3.0.CO;2-W","article-title":"Cre recombinase expression in cerebellar Purkinje cells","volume":"28","author":"Barski","year":"2000","journal-title":"Genesis"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"501","DOI":"10.1016\/0006-8993(71)90457-4","article-title":"Studies on norepinephrine-containing afferents to Purkinje cells of rat cerebellum. 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