Two major troponin I (TnI) genes, fetal TnI (ssTnI) and adult TnI (cTnI), are expressed in the mammalian heart under the control of a developmentally regulated program. In this study, the up-stream domain (~1,800 bp) of mouse fetal TnI gene has been cloned and characterized. There is a high homology of this region among mouse, rat and human. Transfection assays indicated that conserved GA-rich sequences, CREB and a CCAAT box within the first 300 bp upstream of the transcription start site were critical for the gene expression. Electrophoretic mobility shift assays (EMSAs) and chromatin immunoprecipitation (ChIP) assays revealed binding proteins to CREB site in nuclear extracts from myocardial cells. Thyroid hormone (T3) caused a significant inhibitory effect on ssTnI expression in myocardial cells. Cardiac troponin I (cTnI) mutations have been linked to the development of restrictive cardiomyopathy (RCM) in human patients. We modeled one mutation in human cTnI Cv terminus, arginine1 92 histidine (R192H) by cardiac specific expression of the mutated protein (cTnI193His in mouse sequence) in transgenic mice. The main functional alteration detected in cTnI193His mice by ultrasound cardiac imaging examinations was impaired cardiac relaxation manifested by a decreased left ventricular end diastolic dimension (LVEDD) and an increased end diastolic dimension in both atria. Echocardiography revealed a series of changes on the transgenic mice including a reversed E-to-A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. At the age of 12 months, cardiac output in cTnI193His mice was significantly declined, and some transgenic mice showed congestive heart failure. The negative impact of cTnI193His on ventricular contraction and relaxation was further demonstrated in isolated mouse working heart preparations. / Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO.The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation. The results demonstrate a critical role of the COOH-terminal domain of cTnI in the diastolic function of cardiac muscle. This mouse model provides us with a tool to further investigate the pathophysiology and the development of RCM. / by Jianfeng Du. / Thesis (Ph.D.)--Florida Atlantic University, 2008. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.

The mechanisms that rodents employ to navigate through their environment have been greatly studied. Cognitive mapping theory suggests that animals use distal cues in the environment to navigate to a goal location (place navigation). However, others have found that animals navigate in a particular direction to find a goal (directional navigation). The rodent brain contains head direction cells (HD cells) that discharge according to the head direction of the animal. Navigation by heading direction is disrupted by lesions of the anterodorsal thalamic nuclei (ADN), many of which are HD cells. Aim 1 tested whether male C57BL/6J mice exhibit direction or place navigation in the Morris water maze. Aim 2 tested the effects of temporary inactivation of the ADN on directional navigation. Together, these data indicate that C57BL/6J mice also exhibit preference for directional navigation and suggest that the ADN may be crucial for this form of spatial navigation. / by Sidney Beth Williams. / Thesis (M.A.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

Restrictive cardiomyopathy (RCM) is a heart muscle disease, characterized by diastolic dysfunction. The present dissertation is to understand the mechanisms underlyijng the initiation of diastolic dysfunction and the fast disease progression to early death in a RCM mouse model, the transgenic cTnI193His mouse... These data showed that myocardial ischemia occurred after diastolic dysfunction and before systolic dysfunction which proceeded congestive heart failure. The results demonstrate that myocardial ischemia causing cardiomycete death is a link between the initial diastolic dysfunction and late-stage systolic dysfunction, and accelerates the disease progression to fatal heart failure in the early age. / by Yuejin Li. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

Transgenic mice were generated to express a restrictive cardiomyopathy (RCM) human cardiac troponin I (cTnI) R192H mutation in the heart. My study's objective was to assess cardiac function during the development of diastolic dysfunction and to gain insight into the pathophysiological impact of the RCM cTnI mutation. Cardiac function was monitored in cTnI193His mice and wild-type littermates for a period of 12 months. It progressed gradually from abnormal relaxation to diastolic dysfunction characterized with micro- echocardiography by a reversed E/A ratio, increased deceleration time, and prolonged isovolumetric relaxation time. The negative impact of cTnI193His on cardiac function was further demonstrated in isolated mouse working heart preparations. Dobutamine stimulation increased heart rate in cTnI193His mice but did not improve CO. The cTnI193His mice had a phenotype similar to that in human RCM patients carrying the cTnI mutation characterized morphologically by enlarged atria and restricted ventricle and functionally by diastolic dysfunction. / by Nariman Gobara. / Thesis (M.S.)--Florida Atlantic University, 2009. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2009. Mode of access: World Wide Web.

New neurons are continuously generated in the olfactory system of adult mice, including olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) and interneurons, produced in the subventricular zone (SVZ) and migrated toward olfactory bulb (OB) along rostral migratory stream (RMS). The present study observed the effects of target neuron loss on the life-span and maturation of adult-born OSNs in the OE and on the proliferation, migration and differentiation of SVZ stem cells in the forebrain after eliminating bulb neurons. We found the life-span of newborn neurons in the absence of synaptic targets was shortened, but the timing of maturation was not delayed. In addition, SVZ cells continued to divide and migrate to the damaged bulb, and the migration of newborn cells in the RMS on the contralateral side was delayed at 2 weeks post-BrdU. Also, the proliferation of cells in dentate gyrus of the hippocampus was not affected by OB damage at 3 weeks post-lesion, though lesion affects occurred in the adult SVZ/RMS. / by Huan Liu. / Thesis (M.S.)--Florida Atlantic University, 2008. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2008. Mode of access: World Wide Web.

The rodent hippocampus is critical for processing spatial memory but its contribution to non-spatial, specifically object memory is debated. The cognitive map theory of hippocampal function states that the hippocampus stores relationships of goal locations (places) to discrete items (objects) encountered within environments. Dorsal CA1 place cells were recorded in male C57BL/6J mice performing three variations of the novel object recognition paradigm to define "object-in-context" representation of hippocampal neuronal activity that may support object memory. Results indicate, (i) that place field stability is higher when polarizing environmental cues are provided during object recognition; (ii) hippocampal place fields remain stable throughout the novel object recognition testing without a polarizing cue; and (iii) time dependent effects on stability when objects were dissociated from the context. These data indirectly support that the rodent hippocampus processes object memory, and challenge the view that "object-in-context" representations are formed when mice perform novel object recognition task. / by Herborg Nanna âAsgeirsdâottir. / Thesis (M.A.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

SK channels are small conductance Ca2+-activated K+ channels expressed throughout the CNS. SK channels modulate the excitability of hippocampal CA1 neurons by affecting afterhyperpolarization and shaping excitatory postsynaptic responses. Such SK-mediated effects on activity-dependent neuronal excitability and synaptic strength are thought to underlie the modulatory influence of SK channels on memory encoding. Here,the effect of a new SK1 selective activator, GW542573X, on hippocampal-dependent object memory, contextual and cued conditioning, and trace fear conditioning was examined. The results demonstrated that pre- but not post-training systemic administration of GW542573X impaired object memory and trace fear memory in mice 24 h after training. Contextual and cued fear memory were not disrupted. These current data suggest that activation of SK1 subtype-containing SK channels impairs long-term memory. These results are consistent with converging evidence that SK channel activation suppressed behaviorally triggered synaptic plasticity necessary for encoding hippocampal-dependent memory. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Small conductance Ca2+-activated K+ (SK) channels have been shown to alter the encoding of spatial and non-spatial memory in the hippocampus by shaping glutamatergic postsynaptic potentials and modulating NMDA receptor-dependent synaptic plasticity. When activated, dendritic SK channels reduce hippocampal neuronal excitability and LTP. Similar SK channel properties have been demonstrated in lateral amygdala (LA) pyramidal neurons. Additionally, induction of synaptic plasticity and beta-adrenoreceptor activation in LA pyramidal neurons causes PKA-mediated internalization of SK channels from the postsynaptic density. Chronic activation of the amygdala through repetitive stressful stimuli can lead to excitatory synaptic strengthening that may create permanent hyper-excitability in its circuitry. This mechanism may contribute to a number of mood and anxiety disorders. The selective influence of SK channels in the LA on anxiety and fear conditioning are not known. The thesis project outlined herein examined whether SK channel blockade by bee venom peptide, apamin, during a repetitive acute fear conditioning paradigm was sufficient to alter fear memory encoding and the resulting behavioral outcome. Following the final fear memory test session, mice were tested in the open field immediately after the second fear conditioning test session. The findings indicate that intracranial LA microinfusions of apamin did not affect memory encoding or subsequent anxiety. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

Obstructive sleep apnea (OSA) is a common breathing and sleeping disorder, characterized by repeated episodes of airway obstruction during sleep resulting in intermittent hypoxia (IH). From clinical reports, patients with OSA are associated with behavioral and neuropsychological deficits, including impaired spatial learning memory and cognitive deficiencies. Previous studies proposed that reactive oxygen species (ROS) and apoptosis caused by intermittent hypoxia (IH) contributed to this cognitive deficits. However, the exact mechanism is still poorly understood and not settled. / The endoplasmic reticulum (ER) is a cellular organelle in which all secretory and integral membrane proteins are folded and is also the site where proteins are post-translationally modified in ATP-dependent chaperone-mediated processes. In this study, we hypothesized that ER stress in the hippocampus is initiated in the OSA via elevated levels of ROS. Four groups of adult male mice were used, with two of them exposed to normoxia as control, and the other two exposed to IH treatment, each receiving either vehicle or tauroursodeoxycholic acid (TUDCA), an ER stress inhibitor. Eight-armed radial maze was used to investigate the performance of reference memory during the whole IH/normoxia treatment. After behavior test, long-term potentiation (LTP) was measured to investigate synaptic plasticity in hippocampus. Furthermore, ER stress-associated pro-apoptotic effectors were detected by Western blotting, and ultra-structure of rough ER and the morphology of hippocampal dendritic spines and synapses in the hippocampal CA1 area were observed. / LTP was impaired in the hippocampus after IH treatment, which was rescued by TUDCA. Furthermore, ER stress-associated pro-apoptotic effectors, CHOP and caspase-12, were up-regulated after chronic IH treatment and was abolished by co-infusion of TUDCA. Meanwhile, increased cleaved-caspase-3 after chronic IH treatment was reduced by TUDCA via increased expression of Bcl-2. On the other hand, ultrastructural analysis of rough ER in the hippocampal CA1 revealed IH-induced ER luminal swelling, and was attenuated by TUDCA. In addition, the length of synaptic active zone was significantly reduced after chronic IH treatment and was partially rescued by the application of TUDCA. Golgi staining also showed a decrease in mature dendritic spines in IH group, and reversed by TUDCA. In behavioral analysis, the number of reference memory errors significantly increased after IH treatment and rescued by TUDCA injection. Overall, the data suggest a critical role of ER stress underlying the impairment of long-term synaptic plasticity and neurocognitive deficits in chronic IH. Targeting ER stress could be a potential therapeutic strategy for neural dysfunction in OSA. / On the other hand, neuronal firing, especially robust persistent activity of neuron in hippocampus, is critical role in memory formation. Increased ROS induced by IH has been implicated in long-term potentiation of neural activity. IH could be involved in a variety of K⁺ channels which eventually leads to excitotoxicity by increased Ca2⁺-dependent glutamate release. Although the results were just shown in acute IH treatment, the chronic effect of IH on the firing frequency of hippocampus is still unknown. / Therefore, to investigate the effect of chronic IH treatment on firing activities and local field potentials of hippocampal neurons, implantation of multi-channel micro-wires electrode array into hippocampus of OSA model rat was performed to monitor spontaneous discharge. The results were shown the firing frequency of pyramidal neurons (PNs) was significantly elevated after 8 hours IH in second and third days, on the other hand, interneurons (INs) seem to be more sensitive to intermittent hypoxia since the higher firing frequency was sustained from third day to seventh day after 8 hours IH, however, at the end of 14 days IH treatment, the firing frequencies of PNs and INs are all both dramatically reduced. Meanwhile, the results in this part will enable us to understand the exact change of firing pattern and local field potential during intermittent hypoxia. The percentage of complex burst spikes was decreased after 14 days IH in PNs and the power of theta rhythms was also impaired. It suggests that the disorder of neuronal pattern and the change of local field potential are associated with cognitive impairment in OSA model. After 1 week recovery, the firing frequency of PNs was rescued again, but not for that of INs. We also found that the power of theta rhythms which had an important role in memory formation was weaker after 2 weeks IH treatment, however, the precise mechanism was still unknown. From the effect of intermittent hypoxia on spontaneous discharges and LFP of hippocampal neurons in free moving rat, it may reveal some roles of IH in cognitive impairment via disorder neuronal function in CA1 region. / 阻塞性睡眠呼吸暫停(OSA) 是一種常見的睡眠障礙疾病，這種疾病的主要特徵是在睡眠過程中反復發作的氣道阻塞，從而導致间歇性缺氧(IH)。從臨床報導中發現，OSA患者表現出行為和神經心理缺陷，包括空間學習記憶的受損和認知缺陷。通過之前的研究表明，活性氧(ROS)的增多和細胞凋亡是間歇性缺氧所引起認知功能障礙的主要機制之一，然而，其具體的機制仍不清楚。 / 作為細胞重要的細胞器，內質網是分泌蛋白和膜蛋白折疊組裝的主要場所，同時，由ATP依賴的分子伴侶所介導的蛋白質翻譯後修飾這一過程也主要在內置網中完成。在本課題中，我們假設在OSA模型的海馬組織中，內質網應激的啟動是由於缺氧引起的與活性氧(ROS)的升高。在本課題中，我們使用了四組成年雄性小鼠，其中兩組作為正常對照組，分別接受生理鹽水和牛磺去氧膽酸（一種常用的內質網抑制劑）的腹腔注射，另外兩組接受缺氧處理，同時也分別接受照生理鹽水和牛磺去氧膽酸注射。八臂放射迷宮被用來研究參考記憶的表現。行為學結束之後，長時程增強(LTP)用來測定海馬的突觸可塑性。用免疫印跡的方法檢測內質網應激的相關凋亡蛋白的表達情況，並且觀察海馬CA1區域中，內質網超微結構和海馬樹突棘數目及突觸形態的變化。 / 從實驗結果中，LTP在缺氧後減弱，而TUDCA能夠部分恢復由於缺氧所導致的LTP的降低。除此之外，內質網應激相關的促凋亡蛋白(CHOP和caspase-12)在缺氧組中表達升高，但是在TUDCA組中有所減低，同時，我們還發現，TUDCA也能夠減低缺氧組中cleaved-caspase-3的表達，而這一作用，可能與提高Bcl-2蛋白的表達（一個可標記的抗凋亡蛋白）有關。在間歇性缺氧組的海馬CA1區域中，粗面內質網出現管腔的腫脹，這一超微結構的變化表明在內質網出現官腔中有的許多未折疊蛋白聚集，並通過TUDCA的注射能夠降解未折疊蛋白來緩解這一現象的發生。同時，在IH處理後，突觸超微結構也發生了形態上的變化。突觸活性區的長度在IH處理組中顯著減少，但是在TUDCA組中有一定程度的恢復。高爾基染色顯示，成熟樹突棘（海馬突觸可塑性的結構基礎）的數目在間歇性缺氧組中有所下降，而在TUDCA治療後，成熟樹突棘的數目有所上升。我們發現參考記憶錯誤次數在缺氧後都有明顯的升高，而在注射TUDCA後，參考記憶錯誤次數都有所降低。總之，這些結果證明，內質網應激在間歇性缺氧的所引起的長時程突觸可塑性減弱和神經認知功能的損傷起到關鍵的作用，而抑制內質網應激對OSA中的出現神經功能紊亂起到一定的預防和治療效果。 / 而另一方面，神經元的放電，特別是海馬中神經元穩定持久的放電形式，對記憶的形成起到關鍵的作用。間歇性缺氧所引起的ROS的升高對於長時程增強的神經活動存在一定的關係，因為，通過以往的研究發現，間歇性缺氧可以通過多種鉀離子通道的啟動，最終由於鈣離子依賴的谷氨酸釋放的增多从而導致興奮性毒性的神經遞質的釋放。而這些結果只在急性缺氧模型中發現，慢性的間歇性缺氧對海馬的放電頻率的影響仍是未知之數。 / 因此，為了探討長時程的間歇性缺氧對海馬神經元的放電頻率和局部場電位的影響，多管道微絲電極陣列植入OSA大鼠的海馬中來監控自發放電的影響。結果表明，錐體細胞的放電頻率在第二天和第三天的8小時的間歇性低氧後明顯的升高了。另一方面，我們觀察到中間神經元似乎對間歇性缺氧更敏感，因為，從第三天到第七天缺氧8小時後，神經元的放電頻率都明顯的增高。但是在間歇性缺氧14天后，錐體細胞和中間神經元的放電頻率都所有顯著性的減少。同時，這一部分結果準確表明了海馬神經元的放電模式和局部場電位在間歇性缺氧的模型的是如何變化的。我們發現錐體細胞所具有的複合簇狀放電的比例減少，同時，theta波(與記憶的形成有關)的能量也有所減低。而這種神經元活動和局部的場電位的異常變化可能與OSA模型中出現的總認知功能障礙有關。在恢復一周後，錐體細胞的放電頻率有所增加，基本上可以恢復到缺氧前的狀態，但是中間神經元的頻率卻沒有多大的改變, 但是，其具體機制仍不清楚。從間歇性缺氧對大鼠海馬神經元自發放電和場電位影響的結果，它揭示了間歇性缺氧通過擾亂海馬CA1區域神經元的功能從而導致認知功能損傷。 / Xu, Linhao. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2014. / Includes bibliographical references (leaves 167-199). / Abstracts also in Chinese. / Title from PDF title page (viewed on 03, October, 2016). / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only.

Orientador: Ana Silvia Alves Meira Tavares Moura / Banca: Simone Fernandes / Banca: Valderez Bastos Valero-Lapckick / Banca: Denose Rangel da Silva Sartori / Banca: Luiz Edivaldo Pezzato / Resumo: O objetivo deste estudo foi avaliar a preferência e efeito do fornecimento de materiais de nidificação sobre o desempenho reprodutivo de camundongos isogênicos da linhagem BALB/c e da linhagem heterogênica Swiss em sistema de acasalamento intensivo monogâmico. Primeiro foi realizado um estudo para avaliar a preferência dos camundongos pelo material oferecido para nidificação. Utilizou-se um sistema composto de quatro gaiolas, com livre acesso a água e ração, interligados por tubos de PVC que permitiam que os animais se locomovessem entre todas as gaiolas. Quatro tipos de materiais foram oferecidos para a construção do ninho: algodão, gaze, rolinho de papelão, e touca de polipropileno descartável. Cada um dos quatro materiais foi oferecido simultaneamente em uma das quatro gaiolas que compunham o sistema. Foram usados 10 sistemas iguais e cada um abrigou um casal da linhagem BALB/c, desde os 28 dias de idade até o terceiro ciclo reprodutivo. Os mais encontrados na confecção do ninho, em ordem decrescente, foram a touca, rolinho, algodão e gaze (P< 0,0083). Com base nestes resultados foram selecionados dois tipos de materiais para fornecimento aos animais no experimento 2. Embora o rolinho tenha sido o segundo material mais utilizado optou-se pelo algodão devido a inviabilidade de fornecimento do item durante todo o período de duração do experimento 2. O segundo experimento avaliou a eficiência reprodutiva em cinco ciclos reprodutivos do nascimento até o desmame. Usou-se 60 casais de irmãos completos da linhagem BALB/c (isogênica) e 60 casais formados por acasalamentos aleatórios da linhagem Swiss (heterogênica) de padrão sanitário controlado, criados e mantidos em ambiente padronizado. Eles foram distribuídos, num delineamento inteiramente casualizado, em arranjo fatorial 2x2 (duas linhagens em alojamento com ou sem material para nidificação). Como forma de ... / Abstract: The objective of this study was to evaluate the preference and effect of nesting materials provision on performance of inbred mice of the BALB/c strain and of heterogenic Swiss in intensive monogamous mating system. Firstly, a study was conducted to evaluate the preference of mice for the material offered for nesting. A system composed of four cages was used, with free access to water and food, connected by PVC tubing, which allowed animal displacement among all cages. Four types of materials were available for construction of the nest: cotton, gauze, cardboard rolls, and disposable polypropylene cap. Each of the four materials was offered simultaneously in one of four cages that formed the system. Ten identical system were used and each one housed a BALB/c couple, from 28 days of age up to the third reproductive cycle. The most commonly found materials in nest making were cap, roll, cotton and gauze (P <0.0083). Based on these results, two types of materials were selected to be offered to the animals in experiment 2. Although the roll was the second most used material, we chose cotton due to unfeasibility supplying of the item throughout the duration of the second experiment. The second experiment evaluated the reproductive efficiency in five reproductive cycles from birth to weaning. Sixty BALB / c full siblings pairs (inbred) and 60 pairs formed by random mating of Swiss strain (outbred), bred and maintained in a standardized environment were used. They were distributed in a completely randomized design in a 2x2 factorial arrangement (two strains in housing with or without nesting material). As a way of cage enrichment, polypropylene disposable cap cut into 8 pieces of approximately 1 cm each and one piece of cotton about 3 g were used after being previously packaged and autoclaved . The following characteristics were evaluated: age at first parturition, litter intervals, pre-weaning mortality and ... / Doutor