Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model.
Age and Sex as Determinants of Acute Domoic Acid Toxicity in a Mouse Model.
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DOI：
10.3390/toxins15040259
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发表时间：
2023-04-01
期刊：
影响因子：
4.2
通讯作者：
Marcinek DJ
中科院分区：
文献类型：
--
作者：
Hendrix AM;Lefebvre KA;Bowers EK;Stuppard R;Burbacher T;Marcinek DJ
兴奋性神经毒素软骨藻酸（DA）一直污染着世界各地沿海地区的食物网。急性暴露于该毒素会导致贝类中毒，这是一种可能致命的胃肠道和泌尿系统相关后果综合征。高龄和男性都被认为是个体间DA易感性的原因。为了测试这一点，我们对成年（7-9个月大）和老年（25-28个月大）生命阶段的雌性和雄性C57 Bl/6小鼠给予0.5至2.5 mg/kg体重的DA剂量，并观察癫痫发作相关活动90分钟，此时我们对小鼠实施安乐死并收集血清、皮质和肾脏样本。我们在一些老年人中观察到严重的阵挛性强直性惊厥，但在年轻人中没有。我们还发现高龄与中重度癫痫相关结局（后肢震颤）的发生率之间存在相关性，高龄与总体症状严重程度和持续性之间也存在相关性。令人惊讶的是，我们还报告说，雌性小鼠，特别是老年雌性小鼠，表现出更严重的神经毒性症状后，急性暴露于DA比男性。年龄和性别模式也反映在组织DA浓度中：老年小鼠和雌性在暴露后90分钟其组织中的DA浓度通常较高。这项研究有助于为受到更频繁和更广泛的DA产生藻类水华威胁的社区提供智能，循证的公共卫生保护。
The excitatory neurotoxin domoic acid (DA) consistently contaminates food webs in coastal regions around the world. Acute exposure to the toxin causes Amnesic Shellfish Poisoning, a potentially lethal syndrome of gastrointestinal- and seizure-related outcomes. Both advanced age and male sex have been suggested to contribute to interindividual DA susceptibility. To test this, we administered DA doses between 0.5 and 2.5 mg/kg body weight to female and male C57Bl/6 mice at adult (7–9-month-old) and aged (25–28-month-old) life stages and observed seizure-related activity for 90 min, at which point we euthanized the mice and collected serum, cortical, and kidney samples. We observed severe clonic–tonic convulsions in some aged individuals, but not in younger adults. We also saw an association between advanced age and the incidence of a moderately severe seizure-related outcome, hindlimb tremors, and between advanced age and overall symptom severity and persistence. Surprisingly, we additionally report that female mice, particularly aged female mice, demonstrated more severe neurotoxic symptoms following acute exposure to DA than males. Both age and sex patterns were reflected in tissue DA concentrations as well: aged mice and females had generally higher concentrations of DA in their tissues at 90 min post-exposure. This study contributes to the body of work that can inform intelligent, evidence-based public health protections for communities threatened by more frequent and extensive DA-producing algal blooms.
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影响因子：
3.4
作者：
Baron, Andrew W.;Rushton, Steven P.;Judge, Sarah J.
通讯作者：
Judge, Sarah J.
DOI：
10.1053/ejso.1998.0650
发表时间：
1999-06-01
期刊：
EUROPEAN JOURNAL OF SURGICAL ONCOLOGY
影响因子：
--
作者：
Mathew, A;Pandey, M;Murthy, NS
通讯作者：
Murthy, NS
影响因子：
5.3
作者：
WETMORE, L;NANCE, DM
通讯作者：
NANCE, DM
影响因子：
4.8
作者：
Gaignard, Pauline;Savouroux, Stephane;Guennoun, Rachida
通讯作者：
Guennoun, Rachida
影响因子：
4.2
作者：
Zheng G;Wu H;Che H;Li X;Zhang Z;Peng J;Guo M;Tan Z
通讯作者：
Tan Z