[Show abstract][Hide abstract] ABSTRACT: Diabetes mellitus is associated with adverse complications in many organ systems including the brain. Accumulating evidence indicates that diabetes, regardless of its type, impairs adult neurogenesis in the dentate gyrus (DG) of the hippocampus (HPC). However, the effects of the disease on neurogenesis in the subventricular zone (SVZ) are not well established. We induced diabetes in male NOD/SCID (non-obese diabetic/severe combined immunodeficiency) mice and C57BL/6 mice with a single intraperitoneal injection of streptozotocin (STZ). On day 7 or day 21 after STZ injection mice received the thymidine analog 5-bromo-2'-deoxyuridine (BrdU) for labeling of proliferative cells. Mice were sacrificed 24h later and brain coronal sections were stained with anti-BrdU antibodies. Neural stem/progenitor cell (NSC/NPC) proliferation, as revealed by BrdU-labeled cells, was markedly decreased in the subgranular zone of the DG in STZ-treated diabetic mice. A similar reduction of NSC/NPC proliferation was seen in the SVZ. Reduced DG and SVZ cell proliferation was also found in diabetic NOD mice, a model of spontaneous diabetes, and the reduction was attenuated by bilateral adrenalectomy (Adx). Adx did not alter blood glucose or insulin levels in either prediabetic or diabetic NOD mice, but Adx partly increased mRNA levels of hippocampal and SVZ brain-derived neurotrophic factor (BDNF), a crucial regulator of NSC/NPC proliferation. Moreover, NOD and NOD/SCID mice showed a more rapid reduction of NSC/NPC proliferation than C57BL/6 mice in response to diabetes. Thus, we conclude that diabetes inhibits cell proliferation in both the SVZ and HPC, and inhibition was associated with elevated glucocorticoid levels and reduced BDNF expression.
Neuroscience Research 12/2010; 68(4):329-36. DOI:10.1016/j.neures.2010.08.012 · 1.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies show a high prevalence of obstructive sleep apnea (OSA) patients with a higher non-rapid eye movement (NREM) apnea-hypopnea index (AHI) (NREM-AHI) than rapid eye movement (REM) AHI (REM-AHI). However, the clinical significance of this phenomenon in patients with OSA is unknown. This study aimed to investigate whether there were significant differences in clinical and polysomnographic features between the NREM-AHI > REM-AHI group and the REM-AHI > NREM-AHI group and to determine whether NREM-AHI > REM-AHI or REM-AHI > NREM-AHI is a specific clinical entity.
One hundred forty-two patients with OSA, including 114 males and 28 females, were assessed for specific sleep-related complaints using a semistructured clinical questionnaire, for daytime sleepiness using the Epworth Sleepiness Scale (ESS), for depression using the Beck Depression Inventory (BDI), and for health-related quality of life using the Medical Outcomes Study Short-Form 36 Health Survey questionnaire (SF-36). Anthropometric, clinical, and polysomnographic characteristics were examined between patients with NREM-AHI > REM-AHI and those with REM-AHI > NREM-AHI.
A higher NREM-AHI than REM-AHI was found in 54.9% of the 142 patients with OSA. Overall, males predominated in each group, and there were no significant differences in age, body mass index, medical history, and drug intake between the NREM-AHI > REM-AHI group and the REM-AHI > NREM-AHI group. A high occurrence of NREM-AHI > REM-AHI (94.9%) or REM-AHI > NREM-AHI (90.6%) was found in moderate-to-severe cases each group. Although several indexes of OSA were worse in the NREM-AHI > REM-AHI group than in the REM-AHI > NREM-AHI group, no significant differences in specific sleep-related complaints, ESS score, BDI score, the incidence of daytime sleepiness or depression, and scores of sub-dimensions and the total score on SF-36 were present between the two groups. As compared separately, no significant differences in clinical features were observed in the clinical data for males and females between the two groups.
Our results show that either NREM-AHI > REM-AHI or REM-AHI > NREM-AHI is more common in moderate-to-severe OSA cases, and there are no significant differences in clinical features between the NREM-AHI > REM-AHI group and the REM-AHI > NREM-AHI group. These findings may suggest that either NREM-AHI > REM-AHI or REM-AHI > NREM-AHI should be considered as a part of the spectrum of OSA, rather than a specific clinical entity.
Sleep And Breathing 05/2010; 15(3):463-70. DOI:10.1007/s11325-010-0358-z · 2.48 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A key event in the pathogenesis of Alzheimer's disease (AD) is the conversion of the peptide beta-amyloid (Abeta) from its soluble monomeric form into various aggregated morphologies in the brain. Apolipoprotein E (apoE) is known to act as a pathological chaperone of Abeta in this process, promoting its fibril formation from soluble Abeta by binding interaction between carboxy-terminal domain of apoE and residues 12-28 of full-length Abeta. Therefore, blocking apoE/Abeta interaction is being actively pursued as a primary therapeutic strategy for AD. Abeta20-29, a short peptide, contains the residues to competitively bind to apoE and may potentially block the interaction between apoE and full-length Abeta. However, little is known whether Abeta20-29 could block apoE/Abeta interaction to play an effective role in reducing full-length Abeta fibrillization and cytotoxicity. Utilizing fluorescence spectroscopic analysis with thioflavin T and electron microscopic study, we show here that Abeta20-29 alone was non-fibrillogenic, and had no direct effects on Abeta1-42 or Abeta1-40 aggregation. Moreover, apoE can directly promote both Abeta1-42 and Abeta1-40 aggregation and fibril formation, while this promoting effect was inhibited when adding Abeta20-29, with a dose-dependent manner. In the series of cell culture experiments, Abeta20-29 alone shows no cytotoxicity to PC12 cells as demonstrated by MTT assay, while co-incubation apoE isoforms and Abeta1-42 or Abeta1-40 shows stronger cytotoxicity as compared to Abeta1-42 or Abeta1-40 alone. When incubated with Abeta20-29, whereas such strong cytotoxic effect was concentration-dependently reduced. Taken together, we demonstrate for the first time that Abeta20-29 has no direct effect on full-length Abeta aggregation, and may competitively block the binding of full-length Abeta to apoE, resulting in an inhibitory effect on apoE's promoting full-length Abeta fibrillogenesis and Abeta-induced cytotoxicity. Our results raise the possibility that Abeta20-29 peptide blocking the interaction between full-length Abeta and apoE isoforms may be effective as a therapeutic agent for AD.
[Show abstract][Hide abstract] ABSTRACT: Acute exacerbation of generalized myasthenia gravis (GMG) can cause swallowing impairment, respiratory failure, or death. It is important to identify immunological factors that might be regarded reliably as an index of the patient's clinical condition, response to treatment, and measure of certain immune aberrations of MG. In this study we investigated correlations between complement component C3, acetylcholine receptor antibody (AChRab) titer, and clinical severity of GMG. AChRab titer and C3 concentration were determined by radioimmunoassay and nephelometry, respectively. The clinical severity of GMG was assessed by the quantitative MG score (QMGS) according to Besinger and colleagues. Our findings indicate that the C3 level correlates with clinical severity of AChRab-positive GMG.
[Show abstract][Hide abstract] ABSTRACT: Movement disorders are known to be associated with hyperthyroidism. However, the association of Meige's syndrome and hemichorea with hyperthyroidism has not been reported. We describe a young Chinese woman with hyperthyroidism, who presented with a unique combination of Meige's syndrome and hemichorea in the left limbs. Both neurologic manifestations were preceded by symptoms of hyperthyroidism, and resolved following treatment with methimazole for hyperthyroidism. Nevertheless, the neurologic symptoms recurred when she stopped taking methimazole, but abated when she returned to a euthyroid state after additional treatment with methimazole. The evolution of her clinical course indicated that the involuntary movements were in association with hyperthyroidism. This case is the first report of Meige's syndrome and hemichorea in a patient with hyperthyroidism, which raises the likelihood that hyperthyroidism may be a cause of Meige's syndrome and hemichorea. Furthermore, it emphasizes the need for greater attention to thyroid function in those afflicted with involuntary movements in order to optimize clinical management.
Journal of the neurological sciences 10/2009; 288(1-2):175-7. DOI:10.1016/j.jns.2009.10.018 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rhythmic movement disorder (RMD) refers to a group of stereotyped, repetitive movements involving large muscles, usually occurring prior to the onset of sleep and persisting into sleep. RMD more commonly exhibits only one or two forms of rhythmic movements (RM) in most reported cases. However, multiple RM forms of RMD occurring in a patient in the same night have rarely been reported. In this report, we present the unique case of a 15-year-old boy with RMD affected by multiple forms of RM in the same night, including four known forms (i.e., body rocking, head banging, leg rolling, and rhythmic feet movements) and two new kinds of RM (bilateral rhythmic arm rocking and rhythmic hands movements). Two video-polysomnographic recordings were performed in this patient before starting pharmacologic treatment and after long-term oral clonazepam treatment (1.0mg nightly for 3 months). The characteristics of RMD with multiple RM forms and the effectiveness of clonazepam on the RM episodes and polysomnographic findings observed in our patient are discussed. This report raises the fact that a patient with RMD may present with multiple complex rhythmic movements disrupting sleep, which emphasizes that better understanding of the clinical features of complex rhythmic movements during sleep in primary care settings is essential for early clinical diagnosis and optimal management.
[Show abstract][Hide abstract] ABSTRACT: Muscle carnitine deficiency usually results in a lipid storage myopathy, but more rarely, neuropathy occurs in this condition. We report herein a 29-year-old man with muscle carnitine deficiency who developed not only a lipid storage myopathy, but also a severe sensory neuropathy. Oral therapy with levo-carnitine (3 g per day) for 3 months produced a remarkable improvement of the myopathy and sensory neuropathy. Six months later, he remained in good condition under strict dietary control. This report emphasizes that severe neuropathy may occur in some patients with muscle carnitine deficiency, and highlights the need for the neurologist's familiarity with those afflicted to achieve optimal clinical management.
[Show abstract][Hide abstract] ABSTRACT: It has been reported that autoimmune inflammatory processes in human multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), may induce an alteration in neurogenesis. Studies with transgenic EAE mice have demonstrated an enhancement of neurogenesis in the subventricular zone (SVZ). In contrast, a reduction of stem cell proliferation in the same region has been observed by Pluchino et al. [Brain 2008;131:2564-2578] in myelin oligodendrocyte glycoprotein (MOG)-induced EAE mice. We immunized female C57BL/6 mice with MOG 35-55 peptide and successfully developed chronic/nonremitting EAE, which is believed to be analogous to the progressive form of MS. On day 21 postimmunization, coronal brain sections were collected and stained with anti-5-bromo-2'-deoxyuridine (BrdU) antibody. By counting the number of BrdU-labeled cells, we demonstrated that the neural stem/progenitor cell (NSC/NPC) proliferation decreased in the SVZ, which basically confirms the study of Pluchino et al. on the changes in the SVZ. A reduction of NSC/NPC proliferation also occurred in the hippocampal subgranular zone of the dentate gyrus. The hippocampus is well known to be an important region involved in learning and memory; thus, our finding may offer a possible explanation for the cognitive impairment in human chronic MS.
[Show abstract][Hide abstract] ABSTRACT: Synaptic dysfunction induced by amyloid-beta protein (Abeta) has been shown to play a critical role in cognitive deficits of Alzheimer's disease (AD). Currently, however there is no clinical causative therapy for the disease. S14G-humanin (HNG) is best known for its strong neuroprotective ability against AD-related insults in vitro, and several in vivo studies have shown its effectiveness in ameliorating the cognitive impairment, but the precise mechanism of HNG on neuroprotection still remains to be elucidated. The present study examined the effects of HNG on Abeta-induced inhibition of hippocampal long-term potentiation (LTP) in mouse hippocampal slices. The results disclosed that soluble Abeta(25-35) significantly inhibited the induction of early-phase LTP (E-LTP) and late-phase LTP (L-LTP) in the hippocampal CA1 region without affecting the basal synaptic transmission, while HNG significantly ameliorated such inhibition of E-LTP and L-LTP in a dose-dependent manner. In addition, the reduction of phosphorylated CREB trigged by Abeta(25-35) was restored by HNG during L-LTP induction, possibly attributing to the improvement of the L-LTP inhibition. Collectively, our findings add to the evidence that soluble Abeta-induced LTP inhibition may represent an early pathological event of AD, and demonstrate for the first time that HNG may improve LTP inhibition by subneurotoxic concentration of soluble Abeta, suggesting that HNG may have therapeutic potential for Abeta-induced synaptic dysfunction closely associated with cognitive deficits in the early stage of AD.
[Show abstract][Hide abstract] ABSTRACT: A 21-year-old woman, who experienced manual strangulation, developed delayed parkinsonism associated with a selective symmetric basal ganglia lesion. The patient had recovered completely one year after early combination therapy. This case emphasizes the need for greater attention in detecting early brain injuries in those afflicted with strangulation so as to provide optimal management.
[Show abstract][Hide abstract] ABSTRACT: Decay accelerating factor (DAF) is a very potent complement regulatory protein which holds promise for clinical usage. Here we report on an improved procedure for refolding both rat and human DAF over-expressed in Escherichia coli. It was shown that 50-70% of the inclusion body could be refolded to soluble active protein. This method excludes the use of L-arginine, which is expensive, and can be used to prepare a large quantity of recombinant DAF for therapeutic studies.
Protein Expression and Purification 03/2009; 66(1):102-6. DOI:10.1016/j.pep.2009.02.014 · 1.70 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Parry-Romberg syndrome (PRS) is a rare clinical entity of unknown etiology, generally characterized by a slow and progressive atrophy that affects 1 side of the face. A variety of neurologic abnormalities have been shown to coexist with PRS. However, few studies regarding pyramidal tract involvement in this disorder have been reported. We report a unique case, in which the patient presented with bilateral pyramidal tract insult and an unusual sequence of disease onset and progression. This case suggests a rarer variant of PRS, and the neurologic findings indicate that the underlying essential neural degeneration may contribute to the processing of pyramidal tract insult or this syndrome.
The American Journal of the Medical Sciences 02/2009; 337(3):212-4. DOI:10.1097/MAJ.0b013e31818226f9 · 1.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cerebral amyloid-beta protein (Abeta) deposition and associated neuroinflammation and apoptosis are increasingly recognized as an important component leading to cognitive impairment in Alzheimer's disease (AD). Humanin (HN) and its derivative, S14G-HN (HNG), are best known for their ability to suppress neuronal death induced by AD-related insults in vitro. Furthermore, limited in vivo studies show that HNG can ameliorate memory impairment induced by intracerebroventricular injection of anti-cholinergic drugs or Abeta25-35. However, the mechanism underlying the in vivo effect remains unclear. In this study, we sought to determine the effects of HNG on neuroinflammatory responses and apoptosis associated with behavioral deficits induced by Abeta25-35 in vivo. Our results indicate that intracerebroventricular injection of aggregated Abeta25-35 induced impairment of learning and memory, markedly elevated numbers of reactive astrocytes, activated microglia, and apoptotic cells, as well as remarkable increased levels of IL-6 and TNFalpha. Moreover, intraperitoneal HNG treatment ameliorated behavioral deficits, and reduced neuroinflammatory responses and apoptotic cells in the brain. Cumulatively, these finding demonstrate for the first time that HNG may have the potential for attenuating Abeta-induced cognitive deficits by reducing inflammatory responses and apoptosis in vivo, which may add to the novel evidence for anti-inflammatory and antiapoptosis properties of HNG in AD treatment.
[Show abstract][Hide abstract] ABSTRACT: Neurocutaneous melanosis (NCM) rarely begins in adulthood. Due to the late onset of neurologic symptomology, a prompt diagnosis is often misleading or delayed, particularly in patients with pure leptomeningeal involvement. We describe herein a 25-year-old patient with congenital giant melanocytic nevi at birth, presenting with diffuse leptomeningeal melanocytic involvement, particularly within the basilar region of the brain. He developed a rapid increase in the size of the lesion over a short period of time, leading to rapid deterioration and death. The neuroradiologic feature in this case was unusual compared with previously reported adult cases of NCM. This case illustrates the importance of considering the likelihood of underlying NCM when evaluating adult patients with neurologic symptoms and cutaneous melanosis.
[Show abstract][Hide abstract] ABSTRACT: Brown-Vialetto-Van Laere (BVVL) syndrome is a rare disorder with clinical features that include progressive bilateral sensorineural deafness and a variety of cranial nerve impairments. Respiratory compromise has been observed in most familial and sporadic cases; however, few studies have been published regarding sleep-disordered breathing in this syndrome. We report the unique case of a 16-year-old girl with the clinical features of BVVL syndrome who presented with bilateral sensorineural hearing loss and then progressively developed paralysis of the 7th and 9th-12th cranial nerves. More importantly, she presented with the unusual feature of severe sleep-disordered breathing. A polysomnographic study showed evidence of dominant central sleep apnea, and the majority of apneic episodes more likely occurred in stage 2 during NREM sleep. The central sleep apnea was associated with rapid respiratory deterioration and death. This report raises the fact that a patient with BVVL syndrome may present with severe sleep-disordered breathing as a life-threatening condition, which emphasizes the need for greater attention to the early detection of potential sleep-disordered breathing in these afflicted with the BVVL syndrome for optimal clinical management.
Journal of the Neurological Sciences 01/2008; 263(1-2):214-7. DOI:10.1016/j.jns.2007.06.032 · 2.47 Impact Factor