{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T22:38:25Z","timestamp":1761863905961,"version":"3.41.2"},"reference-count":43,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,12,18]],"date-time":"2018-12-18T00:00:00Z","timestamp":1545091200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100013116","name":"Merz Pharmaceuticals","doi-asserted-by":"crossref","award":["Partial Unrestricted Grant"],"award-info":[{"award-number":["Partial Unrestricted Grant"]}],"id":[{"id":"10.13039\/501100013116","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2019,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Modulation of electrical activity in the subthalamic nucleus has been therapeutically effective in Parkinson's disease. Pharmacological manipulation of glutamate release from subthalamic neurons could also favourably alter basal ganglia activity to improve motor symptoms. This study investigates the efficacy of selective suppression of hyperactive glutamatergic input from the subthalamic nucleus to the globus pallidus internal segment by botulinum toxin A (BoNT\u2010A) in a parkinsonian model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Unilateral 6\u2010hydroxydopamine lesioned parkinsonian rodents and controls received microinfusions of BoNT\u2010A or vehicle into the ipsilateral internal globus pallidus (n\u00a0=\u00a08 per group). Changes in gait were measured by the CatWalk apparatus, along with assessment of apomorphine\u2010induced rotational behaviour prior to and following BoNT\u2010A injection. Immunofluorescent staining for markers of glutamatergic, GABAergic and total terminals was performed at the internal globus pallidus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Administration of a single dose of BoNT\u2010A (0.5\u00a0ng) significantly improved the rotational asymmetry and gait abnormalities. Ameliorations in speed, body speed variation, cadence and walking pattern were comparable to pre\u2010lesioned animals, and persisted up to 1\u00a0month following BoNT\u2010A injection. These changes are associated to BoNT\u2010A's ability to selectively target glutamatergic terminals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Blockade of subthalamic hyperactivity by BoNT\u2010A leads to sufficient reorganization in the basal ganglia needed to generate a consistent rhythmic pattern of walking. This suggests the potential use of intracerebral BoNT\u2010A to produce effective neuromodulation in the parkinsonian brain, as well as expansion into other neurodegenerative disorders linked to excitotoxity.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.13230","type":"journal-article","created":{"date-parts":[[2018,12,3]],"date-time":"2018-12-03T08:08:25Z","timestamp":1543824505000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Intrapallidal injection of botulinum toxin A recovers gait deficits in a parkinsonian rodent model"],"prefix":"10.1111","volume":"226","author":[{"given":"Adrianna R.","family":"Tsang","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology Western University London Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nagalingam","family":"Rajakumar","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology 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