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Friday, September 29, 2023 9:24:24 AM
Interesting, but not (yet) lucrative.
https://pubmed.ncbi.nlm.nih.gov/37698934/
JCI Insight. 2023 Sep 12;e162468. doi: 10.1172/jci.insight.162468. Online ahead of print.
Isradipine therapy in Cacna1dIle772Met/+ mice ameliorates primary aldosteronism and neurologic abnormalities
Abstract
Somatic gain-of-function mutations in the L-type calcium channel CaV1.3 (CACNA1D gene) cause adrenal aldosterone-producing adenomas and micronodules. De novo germline mutations are found in a syndrome of primary aldosteronism, seizures and neurologic abnormalities (PASNA) as well as in autism spectrum disease. Using CRISPR/Cas9, we here generated mice with a Cacna1d gain-of-function mutation found in both adenomas and PASNA syndrome (Cacna1dIle772Met/+). These mice show reduced body weight and increased mortality from weaning to approximately 100 days of age. Male mice do not breed, likely due to neuromotor impairment, and the offspring of female mice die perinatally, likely due to lack of maternal care. Mice generated by in vitro fertilization show elevated intracellular calcium in the aldosterone-producing zona glomerulosa, an elevated aldosterone:renin ratio and persistently elevated serum aldosterone on a high-salt diet as signs of primary aldosteronism. Anesthesia with ketamine and xylazine induces tonic-clonic seizures. Neurologic abnormalities include hyperlocomotion, impaired performance in the rotarod test, impaired nest building and slight changes in social behavior. Intracellular calcium in the zona glomerulosa, aldosterone levels and rotarod performance respond to treatment with the calcium channel blocker isradipine, with implications for the therapy of patients with aldosterone-producing lesions and with PASNA syndrome.
What is a rotarod test?
In the test, a rodent is placed on a horizontally oriented, rotating cylinder (rod) suspended above a cage floor, which is low enough not to injure the animal, but high enough to induce avoidance of fall. Rodents naturally try to stay on the rotating cylinder, or rotarod, and avoid falling to the ground. The length of time that a given animal stays on this rotating rod is a measure of their balance, coordination, physical condition, and motor-planning. The speed of the rotarod is mechanically driven, and may either be held constant, or accelerated.
![](http://investorshub.advfn.com/uimage/uploads/2023/9/29/shsfwMouse_RotaRod.png)
Here we see a group of ELTP investors during the most recent conference call. One cute little investor fell off the wheel as soon as they introduced Nasrat Hakim. The second cute little investor fell off when he mentioned a "partial application." The third cute little investor fell off at "needle mover." Which cute little investor are you?
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#FreeTacoForShareholders
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