A novel trimeric peptide, Neuropep‐1‐stimulating brain‐derived neurotrophic factor expression in rat brain improves spatial learning and memory as measured by the Y‐maze and Morris water maze

Shin, Min Kyoo,Kim, Hong Gi,Kim, Kil Lyong Blackwell Publishing Ltd 2011 Journal of Neurochemistry Vol.116 No.2

<P> <I>J. Neurochem.</I> (2011) <B>116</B>, 205–216.</P><P><B>Abstract</B></P><P>Abundant studies have shown possible links between low levels of brain‐derived neurotrophic factor (BDNF) and neurological diseases such as Alzheimer’s disease, Parkinson’s disease, and depression, as well as stress and anxiety; therefore, BDNF could be a therapeutic target for neurological disorders. In the present study, a positional scanning‐synthetic peptide combinatorial library was utilized to identify a peptide modulator of BDNF expression in the hippocampal neuronal cell line, H19‐7. A novel tripeptide (Neuropep‐1) induced a significant increase of BDNF mRNA and protein levels in H19‐7 cells. Pre‐treatment of TrkB inhibitor (K252a) did not block Neuropep‐1‐induced BDNF up‐regulation. These results indicate that Neuropep‐1 may up‐regulate BDNF expression that might be independent of the TrkB receptor pathway. Tail vein injection of Neuropep‐1 significantly up‐regulated BDNF expression, TrkB phosphorylation, and its downstream signals including activation of Akt, ERK, and cAMP response element binding in the rat hippocampus. To evaluate improvement of spatial learning and memory (SLM) by Neuropep‐1‐induced BDNF up‐regulation, the Y‐maze and Morris water maze tests were performed. These results showed Neuropep‐1 injection improved SLM performance with increase of BDNF and TrkB expression, activation of TrkB downstream signals in rat hippocampus compared with the control group. However, phosphorylation levels of TrkB were not changed when it was normalized to the level of TrkB expression. The difference on TrkB phosphorylation in Neuropep‐1‐injected rats may be affected by behavioral tests. These results suggest that Neuropep‐1 may improve SLM via activation of the BDNF/TrkB signaling pathway in the rat hippocampus. Therefore, our findings represent that Neuropep‐1 might be a potential candidate for treatment of learning and memory disorders as well as neurological diseases involving the abnormal expression of BDNF.</P>

The distribution of neuron‐specific gene family member 1 in brain and germ cells: Implications for the regulation of germ‐line development by brain

Rengaraj, Deivendran,Lee, Bo Ram,Park, Kyung Je,Lee, Sang In,Kang, Kyung Soo,Choi, Jin Won,Kang, Seok Jin,Song, Gwonhwa,Han, Jae Yong Wiley‐Liss, Inc. 2011 Developmental dynamics Vol.240 No.4

<P><B>Abstract</B></P><P>Vesicular acidification at early endosomes dissociates endocytosed receptor‐ligand complexes. The ligands, receptors, or both are then directed to late endosomes for degradation or recycled back to the plasma membrane. Of neuron‐specific gene (NSG) family members, early endosomal protein neuron‐specific gene family member 1 (NSG1) is the most important in receptor recycling. In this study, we characterized chicken NSG1 (cNSG1). We found several functional sites related to endocytotic machinery in cNSG1 that were highly conserved with most other vertebrate NSG1 proteins. We examined the tissue and duration specificity and the temporal and spatial patterns of c<I>NSG1</I> expression<I>.</I> c<I>NSG1</I> expression was preferentially located in all regions of the brain, neuroendocrine glands, and spinal cord. Unexpectedly, c<I>NSG1</I> expression was strongly detected during male and female germ‐line development. Expression of <I>NSG1</I> in two apparently unrelated cell types such as neurons and germ cells suggests <I>NSG1</I> roles in neurons and germ‐cells chemotaxis and endocytotic machinery. Developmental Dynamics 240:850–861, 2011. © 2011 Wiley‐Liss, Inc.</P>

Microtubule‐associated protein 2, an early blood marker of ischemic brain injury

Park, Dongsun,Joo, Seong S.,Lee, Hong J.,Choi, Kyung‐,Chul,Kim, Seung U.,Kim, Yun‐,Bae Wiley Subscription Services, Inc., A Wiley Company 2012 Journal of neuroscience research Vol.90 No.2

<P><B>Abstract</B></P><P>The aim of this study was to develop a sensitive and rapid blood marker to detect ischemic brain injury, because imaging techniques have a limited capacity to identify lesions during the first crucial hours without massive tissue destruction. Rats were subjected to middle cerebral artery occlusion for various durations (0.5–3 hr), followed by reperfusion. At different time points after ischemia and/or ischemia‐reperfusion, the amounts of glial fibrillary acidic protein (GFAP) and microtubule‐associated protein 2 (MAP2) in the cerebrospinal fluid (CSF) and serum were analyzed by Western blotting. Brain infarction was observed in an ischemia‐duration‐dependent manner. GFAP was drastically increased in the CSF 24 and 48 hr after reperfusion, without change in the serum level. Serum levels of MAP2 remarkably increased as early as 0.5 hr of ischemia, much earlier than the observation of minimal tissue injury 3 hr following occlusion. The serum MAP2 level was further increased by a short period (2 hr) of reperfusion, even in 0.5‐ and 1‐hr ischemic rats, despite not observing any typical tissue injuries 24 hr after reperfusion. These results indicate that the MAP2 protein may be able to detect early neuronal injuries, because the level of this protein in the blood spikes before the appearance of visible macrolesions. Therefore, MAP2 could potentially be used as a novel early marker for the detection of a neurotoxic insult. © 2011 Wiley Periodicals, Inc.</P>

Effects of pyridoxine on a high‐fat diet‐induced reduction of cell proliferation and neuroblast differentiation depend on cyclic adenosine monophosphate response element binding protein in the mouse dentate gyrus

Yoo, Dae Young,Kim, Woosuk,Yoo, Ki‐,Yeon,Nam, Sung Min,Chung, Jin Young,Yoon, Yeo Sung,Won, Moo‐,Ho,Hwang, In Koo Wiley Subscription Services, Inc., A Wiley Company 2012 JOURNAL OF NEUROSCIENCE RESEARCH - Vol.90 No.8

<P><B>Abstract</B></P><P>In this study, we challenged pyridoxine to mice fed a high‐fat diet (HFD) and investigated the effects of pyridoxine on HFD‐induced phenotypes such as blood glucose, reduction of cell proliferation and neuroblast differentiation in the dentate gyrus using Ki67 and doublecortin (DCX), respectively. Mice were fed a commercially available low‐fat diet (LFD) as control diet or HFD (60% fat) for 8 weeks. After 5 weeks of LFD or HFD treatment, 350 mg/kg pyridoxine was administered for 3 weeks. The administration of pyridoxine significantly decreased body weight in the HFD‐treated group. In addition, there were no significant differences in hepatic histology and pancreatic insulin‐immunoreactive (‐ir) and glucagon‐ir cells of the HFD‐treated group after pyridoxine treatment. In the HFD‐fed group, Ki67‐positive nuclei and DCX‐ir neuroblasts were significantly decreased in the dentate gyrus compared with those in the LFD‐fed mice. However, the administration of pyridoxine significantly increased Ki67‐positive nuclei and DCX‐ir neuroblasts in the dentate gyrus in both LFD‐ and HFD‐fed mice. In addition, the administration of pyridoxine significantly increased the protein levels of glutamic acid decarboxylase 67 (GAD67) and brain‐derived neurotrophic factor (BDNF) and the immunoreactivity of phosphorylated cyclic AMP response element binding protein (pCREB) compared with the vehicle‐treated LFD‐ and HFD‐fed mice. In contrast, the administration of pyridoxine significantly decreased HFD‐induced malondialdehyde (MDA) levels in the hippocampus. These results showed that pyridoxine supplement reduced the HFD‐induced reduction of cell proliferation and neuroblast differentiation in the dentate gyrus via controlling the levels of GAD67, pCREB, BDNF, and MDA. © 2012 Wiley Periodicals, Inc.</P>

Differences in motor network dynamics during recovery between supra‐ and infra‐tentorial ischemic strokes

Lee, Jungsoo,Lee, Ahee,Kim, Heegoo,Chang, Won Hyuk,Kim, Yun‐,Hee WILEY-LISS, INC 2018 HUMAN BRAIN MAPPING Vol.39 No.12

<P>Most previous stroke studies have been performed in heterogeneous patient populations. Moreover, the brain network might demonstrate different recovery dynamics according to lesion location. In this study, we investigated variation in motor network alterations according to lesion location. Forty patients with subcortical ischemic stroke were enrolled. Patients were divided into two groups: 21 patients with supratentorial stroke (STS) and 19 patients with infratentorial stroke (ITS). All patients underwent resting‐state functional magnetic resonance imaging and behavioral assessment at 2 weeks and 3 months poststroke. Twenty‐four healthy subjects participated as a control group. To compare altered connectivity between groups, measures used in previous studies to evaluate interhemispheric balance and global network reorganization were investigated and the relationship between network measures and motor functions were examined. Cortico‐cerebellar connectivity was also extracted to investigate its relationship with interhemispheric connectivity. In the STS group, measures related to interhemispheric balance were disrupted compared to the control group 2 weeks poststroke, while this was not found in the ITS group. During recovery, measures related to global network reorganization in the STS group and measures related to interhemispheric balance in the ITS group demonstrated significant changes, respectively. Moreover, motor functions were correlated with altered network measures in both groups. There was an interactive relationship between cortico‐cerebellar and interhemispheric cortical connectivity only in the ITS group. Different changes in the motor network were observed depending on the location of stroke lesions. These results might originate from differences in the interactions between cortico‐cerebellar and interhemispheric connectivity.</P>

On the use of a spin‐echo based double inversion recovery acquisition for the measurement of cortical brain thickness

Nam, Yoonho,Kim, Eung Yeop,Kim, Dong‐,Hyun Wiley Subscription Services, Inc., A Wiley Company 2011 Journal of magnetic resonance imaging Vol.33 No.5

<P><B>Abstract</B></P><P><B>Purpose:</B></P><P>To determine whether a spin‐echo‐based sequence, which are inherently insensitive to magnetic field inhomogeneity, can be used for brain cortical thickness measurement studies.</P><P><B>Materials and Methods:</B></P><P>By using a double inversion recovery (DIR) spin‐echo‐based sequence, cortical thickness estimates were performed from data acquired from seven healthy volunteers. The cortical thickness was also calculated from data acquired using an MPRAGE sequence and the Bland‐Altman analysis was performed for comparison of the two methods. The average signal and contrast to noise ratios (SNR, CNR) of the two methods were also calculated.</P><P><B>Results:</B></P><P>The bias over the entire brain between DIR and MPRAGE was 0.87 ± 0.08 mm. The bias calculated in the major regional lobes were temporal: 0.76 ± 0.09 mm, frontal: 0.89 ± 0.07 mm, parietal: 0.92 ± 0.10 mm, occipital: 0.75 ± 0.12 mm, and cingulate: 0.79 ± 0.10 mm. This thickness difference was due mainly to the boundary difference in the MPRAGE and DIR at the grey matter/cerebral spinal fluid (GM/CSF) regions. The mean SNR and CNR was CNR<SUB>MPRAGE</SUB> = 47.8 ± 8.4 and CNR<SUB>DIR</SUB> = 19.2 ± 2.9, SNR<SUB>MPRAGE</SUB> = 76.8 ± 10.5 and SNR<SUB>DIR</SUB> = 21.1 ± 2.8.</P><P><B>Conclusion:</B></P><P>The study suggests that cortical thickness measurements can be performed using a DIR spin‐echo sequence, which is inherently immune to main field inhomogeneity. Larger thickness measurements were consistently observed in DIR compared with MPRAGE. J. Magn. Reson. Imaging 2011;33:1218–1223. © 2011 Wiley‐Liss, Inc.</P>