Effects of Repeated Citalopram Treatments on Chronic Mild Stress- Induced Growth Associated Protein-43 mRNA Expression in Rat Hippocampus

박상하,최송현,이지민,강승우,신유찬,김현주,김현정,신승건,이민수,신경호 대한약리학회 2008 The Korean Journal of Physiology & Pharmacology Vol.12 No.3

Although growth associated protein-43 (GAP-43) is known to play a significant role in the regulation of axonal growth and the formation of new neuronal connections in the hippocampus, there is only a few studies on the effects of acute stress on GAP-43 mRNA expression in the hippocampus. Moreover, the effects of repeated citalopram treatment on chronic mild stress (CMS)-induced changes in GAP-43 mRNA expression in the hippocampus have not been explored before. To explore this question, male rats were exposed to acute immobilization stress or CMS. Also, citalopram was given prior to stress everyday during CMS procedures. Acute immobilization stress significantly increased GAP-43 mRNA expression in all subfields of the hippocampus, while CMS significantly decreased GAP-43 mRNA expression in the dentate granule cell layer (GCL). Repeated citalopram treatment decreased GAP-43 mRNA expression in the GCL compared with unstressed controls, but this decrease was not further potentiated by CMS exposure. Similar decreases in GAP-43 mRNA expression were observed in CA1, CA3 and CA4 areas of the hippocampus only after repeated citalopram treatment in CMS-exposed rats. This result indicates that GAP-43 mRNA expression in the hippocampus may differently respond to acute and chronic stress, and that repeated citalopram treatment does not change CMS-induced decreases in GAP-43 mRNA expression in the GCL. Although growth associated protein-43 (GAP-43) is known to play a significant role in the regulation of axonal growth and the formation of new neuronal connections in the hippocampus, there is only a few studies on the effects of acute stress on GAP-43 mRNA expression in the hippocampus. Moreover, the effects of repeated citalopram treatment on chronic mild stress (CMS)-induced changes in GAP-43 mRNA expression in the hippocampus have not been explored before. To explore this question, male rats were exposed to acute immobilization stress or CMS. Also, citalopram was given prior to stress everyday during CMS procedures. Acute immobilization stress significantly increased GAP-43 mRNA expression in all subfields of the hippocampus, while CMS significantly decreased GAP-43 mRNA expression in the dentate granule cell layer (GCL). Repeated citalopram treatment decreased GAP-43 mRNA expression in the GCL compared with unstressed controls, but this decrease was not further potentiated by CMS exposure. Similar decreases in GAP-43 mRNA expression were observed in CA1, CA3 and CA4 areas of the hippocampus only after repeated citalopram treatment in CMS-exposed rats. This result indicates that GAP-43 mRNA expression in the hippocampus may differently respond to acute and chronic stress, and that repeated citalopram treatment does not change CMS-induced decreases in GAP-43 mRNA expression in the GCL.

Hippocampus-dependent Task Improves the Cognitive Function after Ovariectomy in Rats

천송희 질병관리본부 2017 Osong Public Health and Research Persptectives Vol.8 No.3

Objectives: Estrogen is an important hormone for cell growth, development, and differentiation by transcriptional regulation and modulation of intracellular signaling via second messengers. The reduction in the estrogen level after ovariectomy may lead to cognitive impairments associated with morphological changes in areas of the brain mediate memory. The aim of the present study was to find out the effect of tasks on the cognitive function after ovariectomy in rats. Methods: The animals used in the experiment were 50 Sprague-Dawley female rats. This study applied a hippocampus-independent task (wheel running) and a hippocampus-dependent task (Morris water maze) after ovariectomy in rats and measured the cognitive performance (objectrecognition and object-location test) and growth-associated protein 43 (GAP-43) and neurotrophin 3 (NT-3) expression in the hippocampus, which is an important center for memory and learning. Results: There were meaningful differences between the hippocampus-independent and hippocampus- dependent task groups for the object-location test and GAP-43 and NT-3 expression in the hippocampus, but not the object-recognition test. However, the hippocampus-independent task group showed a significant improvement in the object-recognition test, compared to the control group. Conclusion: These results suggest that hippocampus-dependent task training after ovariectomy enhances the hippocampus-related memory and cognitive function that are associated with morphological and functional changes in the cells of the hippocampus.

Dorsal and Ventral Hippocampus Differentiate in Functional Pathways and Differentially Associate with Neurological Disease-Related Genes during Postnatal Development

Lee, A-Ram,Kim, Jong-Hwan,Cho, Eunsil,Kim, Mirang,Park, Mikyoung Frontiers Media S.A. 2017 Frontiers in molecular neuroscience Vol.10 No.-

<P>The dorsal and ventral regions of the hippocampus are important in cognitive and emotional processing, respectively. Various approaches have revealed the differential molecular and structural characteristics, and functional roles of the hippocampus. Recent RNA sequencing (RNA-seq) technology has enriched our understanding of the hippocampus by elucidating more detailed information on gene expression patterns. However, no RNA-seq–based study on gene profiles in the developing hippocampus has been reported. Using RNA-seq–based bioinformatic analysis in conjunction with quantitative real-time polymerase chain reaction analysis and a comparison of <I>in situ</I> hybridization data obtained from the Allen Brain Atlas, we provide a thorough analysis of differentially expressed genes in the dorsal and ventral hippocampus at specific developmental ages representing the postnatally maturing hippocampus. Genes associated with particular functional pathways and marker genes for particular neurological diseases were found to be distinctively segregated within either the dorsal or ventral hippocampus at specific or at all developmental ages examined. We also report novel molecular markers enriched in the dorsal or ventral hippocampus. Taken together, this study provides insights into the molecular mechanisms underlying physiological functions linked to the dorsal or ventral hippocampus. The information provided in the study also contributes to a better understanding of brain functions and serves as a resource for future studies on the pathophysiology of dorsal and ventral hippocampal functions.</P>

Generalized equivalent uniform dose-based biological optimization in hippocampus-sparing whole-brain radiation therapy

Won Young Jin,Lee Eungman,Cho Sam Ju,Kim Kyung Su 한국물리학회 2021 THE JOURNAL OF THE KOREAN PHYSICAL SOCIETY Vol.79 No.12

We applied and evaluated a generalized equivalent uniform dose (gEUD)-based optimization method to hippocampus-sparing whole-brain radiation therapy (HS-WBRT) using volumetric modulated arc therapy (VMAT). Thirteen patients treated with WBRT were enrolled. To investigate the optimal value of the parameter “a” of the hippocampus for optimizing gEUD, we changed value from 1 to 40. Using the determined parameter “a” value for the hippocampus, dose-volume (DV)-based optimization and DV-based gEUD optimization (DV-gEUD) were used to generate HS-WBRT plans for 13 patients. According to the gEUD optimization, the plans for organ at risk (OAR) and the target plus OAR were denoted as DV-Upper gEUD optimization and DV-Upper+Target gEUD optimization. We analyzed and compared the dose-volume histogram (DVH) of each generated plan. The mean dosage ( Dmean) of the hippocampus was lowest when the parameter “a” of the hippocampus was 20, with acceptable compromise of the D100% and the Dmax of the hippocampus. The hippocampus D100%, Dmean, and Dmax were reduced to 1.78% (p = 0.014), 2.40% (p = 0.236), and 2.81% (p = 0.207), respectively, when the DV-Upper gEUD optimization was used compared to DV-base optimization and reduced to 4.76% (p = 0.001), 5.84% (p = 0.001), and 6.91% (p = 0.000), respectively, when using the DV-Upper+Target gEUD optimization. Comparing the DV-Upper gEUD and the Upper+Target gEUD optimization, these values were further reduced to 2.99% (p = 0.022), 3.50% (p = 0.059), and 4.18% (p = 0.049), respectively, when the Upper+Target gEUD optimization was used. The DV-gEUD optimization plan showed a better dosimetric profile compared to the DV-based optimization. For HS-WBRT treatment plans using gEUD-based optimization, we recommend that the parameter “a” of the hippocampus be set at 20 and that the gEUD of the OARs and the planning target volume (PTV) be optimized at the same time.

흰쥐 해마에서 경련에 의해 발현 유도된 MKP-1에 의한 MAPK 활성 조절

유범희,강웅구,안용민,정선주,전송희,박주배,김용식 大韓神經精神醫學會 1999 신경정신의학 Vol.38 No.4

연구목적 : 전기경련 충격(Electroconvulsive shock, ECS) 및 카이닌산(kainic acid)에 의한 경련은 흰쥐 해마에서 mitogen activated protein kinase(MAPK)를 활성화시키며, 동시에 MAPK 불활성화 효소인 MAPK phosphatase-1(MKP-1)의 발현을 일으킨다. 이 연구의 목적은 경련에 의해 발현된 MKP-1이 역시 경련에 의해 활성화된 MAPK의 불활성화에 관여하는지를 알아보고자 하는 것이다. 방 법 : 흰쥐에 ECS를 가하여 해마에서 MKP-1 발현을 일으킨 뒤 다시 ECS를 가하고, 두 번째 ECS에 의한 MAPK의 일시적 활성화가 MKP-1의 발현상태에 의해 영향받는지를 알아보았다. 또한 흰쥐에 지속적인 MAPK 활성화 및 MKP-1 발현을 일으키는 카이닌산을 투여한 뒤 해마에서 MKP-1의 발현과 MAPK 활성과의 관계를 알아보았다. 결 과 : ECS후 해마에서 타이로신 인산화 면역블롯 및 효소활성으로 측정한 MAPK의 인산화 및 활성은 MKP-1의 발현이 일어나 있는 경우와 그렇지 않은 경우 사이에 차이를 보이지 않았다. 카이닌산의 투여에 의해 MAPK 활성화가 일어나는 경우, 뒤이어 MKP-1 발현이 일어나지만, 이렇게 발현된 MKP-1은 MAPK 활성을 충분히 감소시키지 못하였다. 결 론 : MKP-1은 흰쥐 해마에서 ECS 및 카이닌산에 의한 MAPK의 활성화를 차단하는데 큰 역할을 하지 않는다. Objectives : Both electroconvulsive shock(ECS)- and kainic acid-induced seizures activate mitogen-activated protein kinases(MAPKs) in rat hippocampus. They can also induce the expression of MAPK phosphatase-1(MKP-1) in rat hippocampus. MKP-1 is known as a specific MAPK deactivator. This study aimed to elucidate the role of MKP-1 in the deactivation of MAPKs in rat hippocampus. Methods : In order to induce MKP-1 in the hippocampus, ECS was given to the rats. At the time points when MKP-1 was sufficiently induced, the second ECS was given to them and the subsequent phosphorylation or activation of MAPKs were measured in the hippocampus. A second group of rats were injected with kainic acid and the relationship between MKP-1 expression and MAPK phosphorylation was examined in their hippocampi. Results : The expression of MKP-1 did not influence the phosphorylation or activation of MAPKs following ECS in rat hippocampus. Kainic acid-induced expression of MKP-1 did not significantly reduce the phosphorylation of MAPKs. Conclusion : MKP-1 did not play a significant role in the deactivation of MAPKs which were activated by ECS or kainic acid in rat hippocampus.

Ischemic Evidence of Transient Global Amnesia: Location of the Lesion in the Hippocampus

양영순,김상윤,김재형 대한신경과학회 2008 Journal of Clinical Neurology Vol.4 No.2

Background and purpose: Transient global amnesia (TGA) is a rare amnestic syndrome characterized by the sudden onset of a selective anterograde and retrograde amnesia with a time course of up to 24 hours. Recent studies have found a high frequency of small high-signal abnormalities in the hippocampus on diffusion-weighted imaging (DWI), and accordingly ischemia has been proposed as an etiology of TGA. We hypothesized that TGA lesions occur preferentially in the CA1 region of the hippocampus, which is known to be susceptible to ischemia. Methods: Twenty consecutive patients with a clinical diagnosis of TGA underwent DWI both within 24 hours of symptom onset and 3 days later. Twenty patients with high-signal abnormalities in the hippocampus on the initial DWI underwent subsequent DWI and T2-weighted imaging in the coronal plane to precisely localize the lesions. Results: Seventeen patients had small high-signal abnormalities (with diameters of 1-3 mm) in the hippocampus unilaterally on DWI. One of these patients had two lesions in one hippocampus. Three of the 20 patients had lesions bilaterally in the hippocampus, 1 of whom had 3 bilateral lesions. A total of 25 lesions were identified: 5 in the hippocampal head, 19 in the body, and 1 in the tail. Six patients had unilateral lesions on the left,11 patients had them on the right, and 3 patients had bilateral lesions. Conclusions: In this study, lesions associated with TGA were localized mostly to the lateral portion of the hippocampus, corresponding to CA1. This finding supports the ischemic etiology of TGA, but the underlying pathophysiologic mechanism requires further investigation.

Comparison of catalase immunoreactivity in the hippocampus between young, adult and aged mice and rats

AHN, JI HYEON,CHEN, BAI HUI,SHIN, BICH-NA,LEE, TAE-KYEONG,CHO, JEONG HWI,KIM, IN HYE,PARK, JOON HA,LEE, JAE-CHUL,TAE, HYUN-JIN,LEE, CHOONG-HYUN,WON, MOO-HO,LEE, YUN LYUL,CHOI, SOO YOUNG,HONG, SEONGKWE D.A. Spandidos 2016 MOLECULAR MEDICINE REPORTS Vol. No.

<P>Catalase (CAT) is an important antioxidant enzyme and is crucial in modulating synaptic plasticity in the brain. In this study, CAT expression as well as neuronal distribution was compared in the hippocampus among young, adult and aged mice and rats. Male ICR mice and Sprague Dawley rats were used at postnatal month (PM) 1, PM 6 and PM 24 as the young, adult and aged groups, respectively (n=14/group). CAT expression was examined by immunohistochemistry and western blot analysis. In addition, neuronal distribution was examined by NeuN immunohistochemistry. In the present study, the mean number of NeuN-immunoreactive neurons was marginally decreased in mouse and rat hippocampi during aging, although this change was not identified to be significantly different. However, CAT immunoreactivity was significantly increased in pyramidal and granule neurons in the adult mouse and rat hippocampi and was significantly decreased in the aged mouse and rat hippocampi compared with that in the young animals. CAT protein levels in the hippocampus were also lowest in the aged mouse and rat hippocampus. These results indicate that CAT expression is significantly decreased in the hippocampi of aged animals and decreased CAT expression may be closely associated with aging.</P>

Anti-oxidative effect of baicalin in lipopolysaccharide-induced hippocampus damage

10.13041/jpvm.2020.44.3.118 한국예방수의학회 2020 예방수의학회지 Vol.44 No.3

Baicalin is a flavonoid compound with many advantages, including anti-inflammatory agents and antioxidants. Lipopolysaccharide (LPS) is an endotoxin that induces neuronal damage through inflammatory response and oxidative stress reaction. This study was investigated the protective effects of baicalin on the oxidative stress and histopathological changes caused by LPS in hippocampus. Adult mice were divided into four groups; vehicle-treated, baicalin-treated, LPS-treated, and LPS and baicalin co-treated animals. Baicalin (10 mg/kg/day) and/or LPS (250 μg/kg/day) were intraperitoneally administered for seven consecutive days, and body weight was measured. Reactive oxygen species (ROS) level and lipid peroxidation level in the hippocampus were examined. Histopathological study was performed using hematoxylin and eosin staining manuals. LPS treatment decreased body weight and increased ROS and oxidative stress in the hippocampus. However, co-treatment with baicalin alleviated these changes caused by LPS. Severe histopathological changes were observed in the hippocampus of LPS-treated animals. Baicalin co-treatment attenuated the changes and preserved neuronal cells from LPS damage. These results showed that baicalin suppresses LPS-induced neuronal damage by alleviating oxidative stress in the hippocampus. Thus, this study demonstrated that baicalin exerts protective effects against LPS-induced oxidative stress in hippocampus.

Siamese Network for Learning Robust Feature of Hippocampi

Samsuddin Ahmed,정호엽(Ho Yub Jung) 한국스마트미디어학회 2020 스마트미디어저널 Vol.9 No.3

Hippocampus is a complex brain structure embedded deep into the temporal lobe. Studies have shown that this structure gets affected by neurological and psychiatric disorders and it is a significant landmark for diagnosing neurodegenerative diseases. Hippocampus features play very significant roles in region-of-interest based analysis for disease diagnosis and prognosis. In this study, we have attempted to learn the embeddings of this important biomarker. As conventional metric learning methods for feature embedding is known to lacking in capturing semantic similarity among the data under study, we have trained deep Siamese convolutional neural network for learning metric of the hippocampus. We have exploited Gwangju Alzheimer’s and Related Dementia cohort data set in our study. The input to the network was pairs of three-view patches (TVPs) of size 32 × 32× 3. The positive samples were taken from the vicinity of a specified landmark for the hippocampus and negative samples were taken from random locations of the brain excluding hippocampi regions. We have achieved 98.72% accuracy in verifying hippocampus TVPs.

Dummy Run of Quality Assurance Program before Prospective Study of Hippocampus-Sparing Whole-Brain Radiotherapy and Simultaneous Integrated Boost for Multiple Brain Metastases from Non-small Cell Lung Cancer: Korean Radiation Oncology Group (KROG) 17-06

정은아,노재명,이규찬,김진희,정원구,서양권,이정애,설기호,우홍균,김연실,노오규,박재원,이동수,이지혜,김영석,박우윤,강민규,조선미,안용찬 대한암학회 2019 Cancer Research and Treatment Vol.51 No.3

Purpose Lung Cancer Subcommittee of Korean Radiation Oncology Group (KROG) has recently launched a prospective clinical trial (KROG 17-06) of hippocampus-sparing whole brain radiotherapy (HS-WBRT) with simultaneous integrated boost (SIB) in treating multiple brain metastases from non-small cell lung cancer. In order to improve trial quality, dummy run studies among the participating institutions were designed. This work reported the results of two-step dummy run procedures of the KROG 17-06 study. Materials and Methods Two steps tested hippocampus contouring variability and radiation therapy planning compliance. In the first step, the variation of the hippocampus delineation was investigated for two representative cases using the Dice similarity coefficients. In the second step, the participating institutions were requested to generate a HS-WBRT with SIB treatment plan for another representative case. The compliance of the treatment plans to the planning protocol was evaluated. Results In the first step, the median Dice similarity coefficients of the hippocampus contours for two other dummy run cases changed from 0.669 (range, 0.073 to 0.712) to 0.690 (range, 0.522 to 0.750) and from 0.291 (range, 0.219 to 0.522) to 0.412 (range, 0.264 to 0.598) after providing the hippocampus contouring feedback. In the second step, with providing additional plan priority and extended dose constraints to the target volumes and normal structures, we observed the improved compliance of the treatment plans to the planning protocol. Conclusion The dummy run studies demonstrated the notable inter-institutional variability in delineating the hippocampus and treatment plan generation, which could be decreased through feedback from the trial center.