Alterations in local thyroid hormone signaling in the hippocampus of the SAMP8 mouse at younger ages: association with delayed myelination and behavioral abnormalities.
Alterations in local thyroid hormone signaling in the hippocampus of the SAMP8 mouse at younger ages: association with delayed myelination and behavioral abnormalities.
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DOI：
10.1002/jnr.23161
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发表时间：
2013-03
影响因子：
4.2
通讯作者：
Tashiro, Tomoko
中科院分区：
文献类型：
--
作者：
Sawano, Erika;Negishi, Takayuki;Aoki, Tomoyuki;Murakami, Masami;Tashiro, Tomoko
加速衰老小鼠（senescence-accelerated mouse，SAM）系是根据衰老表型变异对AKR/J品系进行选择性近交而建立的，包括易衰老（senescence-prone，SAMP）系和抗衰老（senescence-resistant，SAMR）系。其中，SAMP 8被认为是显示与年龄相关的学习和记忆障碍以及改变的情绪状态的神经变性模型。由于成人甲状腺功能减退症是认知障碍和各种精神疾病的常见原因之一，我们研究了甲状腺激素（TH）信号转导可能参与SAMP 8的病理老化，使用抗衰老SAMR 1作为对照。虽然血浆TH水平在两种菌株中相似，但在1至8个月龄的SAMP 8海马中观察到2型脱碘酶（D2）基因表达显著降低，这导致蛋白质水平降低35-50%，其酶活性在1，3和5个月时降低20%。D2负责将甲状腺素局部转化为转录活性的3，5，3 ′-三碘甲状腺原氨酸（T3），因此结果表明SAMP 8海马中T3水平降低。TH依赖性基因的下调和髓鞘碱性蛋白（其表达高度依赖于TH）积累延迟和减少的免疫组化证实了局部TH信号传导的减弱。此外，我们发现多动和焦虑减少与年龄无关，但在他们开始表现出学习和记忆障碍之前，这是年轻SAMP 8的特征。因此，局部TH信号的早期改变可能是行为异常以及SAMP 8病理性衰老的基础。© 2012 Wiley Periodicals，Inc.
The senescence-accelerated mouse (SAM) strains were established through selective inbreeding of the AKR/J strain based on phenotypic variations of aging and consist of senescence-prone (SAMP) and senescence-resistant (SAMR) strains. Among them, SAMP8 is considered as a model of neurodegeneration displaying age-associated learning and memory impairment and altered emotional status. Because adult hypothyroidism is one of the common causes of cognitive impairment and various psychiatric disorders, we examined the possible involvement of thyroid hormone (TH) signaling in the pathological aging of SAMP8 using the senescence-resistant SAMR1 as control. Although plasma TH levels were similar in both strains, a significant decrease in type 2 deiodinase (D2) gene expression was observed in the SAMP8 hippocampus from 1 to 8 months of age, which led to a 35–50% reductions at the protein level and 20% reduction of its enzyme activity at 1, 3, and 5 months. D2 is responsible for local conversion of thyroxine into transcriptionally active 3,5,3′-triiodothyronine (T3), so the results suggest a reduction in T3 level in the SAMP8 hippocampus. Attenuation of local TH signaling was confirmed by downregulation of TH-dependent genes and by immunohistochemical demonstration of delayed and reduced accumulation of myelin basic protein, the expression of which is highly dependent on TH. Furthermore, we found that hyperactivity and reduced anxiety were not age-associated but were characteristic of young SAMP8 before they start showing impairments in learning and memory. Early alterations in local TH signaling may thus underlie behavioral abnormalities as well as the pathological aging of SAMP8. © 2012 Wiley Periodicals, Inc.
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DOI：
10.1016/j.biocel.2011.05.016
发表时间：
2011-10
影响因子：
4
作者：
Arrojo e Drigo, Rafael;Bianco, Antonio C.
通讯作者：
Bianco, Antonio C.
DOI：
10.1093/geronj/47.2.b52
发表时间：
1992-03-01
期刊：
JOURNALS OF GERONTOLOGY
影响因子：
--
作者：
FLOOD, JF;MORLEY, JE
通讯作者：
MORLEY, JE
影响因子：
4.8
作者：
Lamirand, Audrey;Pallud-Mothre, Sophie;Courtin, Francoise
通讯作者：
Courtin, Francoise
影响因子：
4.2
作者：
Colas, D;Cespuglio, R;Sarda, N
通讯作者：
Sarda, N
DOI：
10.1111/j.1749-6632.1996.tb39080.x
发表时间：
1996-01-01
期刊：
PHARMACOLOGICAL INTERVENTION IN AGING AND AGE-ASSOCIATED DISORDERS
影响因子：
--
作者：
Nomura, Y;Yamanaka, Y;Ihara, Y
通讯作者：
Ihara, Y