Different Brain Regions Of Patients Research Articles

Differences in the distribution of triggers among resting state networks in patients with juvenile myoclonic epilepsy explained by network analysis.

Juvenile myoclonus epilepsy (JME) is an idiopathic generalized epilepsy syndrome. Functional connectivity studies based on graph theory have demonstrated changes in functional connectivity among different brain regions in patients with JME and healthy controls. However, previous studies have not been able to clarify why visual stimulation or increased cognitive load induces epilepsy symptoms in only some patients with JME. This study constructed a small-world network for the visualization of functional connectivity of brain regions in patients with JME, based on system mapping. We used the node reduction method repeatedly to identify the core nodes of the resting brain network of patients with JME. Thereafter, a functional connectivity network of the core brain regions in patients with JME was established, and it was analyzed manually with white matter tracks restriction to explain the differences in symptom distribution in patients with JME. Patients with JME had 21 different functional connections in their resting state, and no significant differences in their distribution were noted. The thalamus, cerebellum, basal ganglia, supplementary motor area, visual cortex, and prefrontal lobe were the core brain regions that comprised the functional connectivity network in patients with JME during their resting state. The betweenness centrality of the prefrontal lobe and the visual cortex in the core functional connectivity network of patients with JME was lower than that of the other brain regions. The functional connectivity and node importance of brain regions of patients with JME changed dynamically in the resting state. Abnormal discharges originating from the thalamus, cerebellum, basal ganglia, supplementary motor area, visual cortex, and prefrontal cortex are most likely to lead to seizures in patients with JME. Further, the low average value of betweenness centrality of the prefrontal and visual cortices explains why visual stimulation or increased cognitive load can induce epileptic symptoms in only some patients with JME.

Differences in diffusion tensor imaging parameters of brain white matter tracts between patients with myotonic dystrophy type 1 and type 2 - a retrospective single-centre study.

The main aim of our study was to compare diffusion tensor imaging (DTI) parameters in patients with myotonic dystrophy types 1 and 2 (DM1 and DM2). To ascertain whether DTI could be used to assess the integrity of white matter tracts in the brain and identify any abnormalities or disruptions in connectivity between different brain regions in patients with DM. By providing a more detailed understanding of the structural changes in the brain associated with DM, could DTI potentially be used to develop more effective treatments for the cognitive and neurological symptoms of the disorder? We retrospectively compared MRI scans of 19 patients with DM1 to those of 23 healthy, matched controls, and of 16 patients with DM2 to those of 20 healthy, matched controls, and finally compared the DM1 and DM2 samples. Fraction anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) values were assessed using Tract Based Spatial Statistics (TBSS). In patients with DM1, a statistically significant decrease in the values of the FA parameter was revealed in 45/48 white matter tracts compared to patients with DM2. There was no statistically significant decrease in the values of the FA parameter in patients with DM2 compared to DM1. The values of MD and RD were significantly higher in 47 tracts in DM1 patients compared to DM2 patients. AD values were significantly higher in all 48 tracts in DM1 patients compared to DM2 patients. There were no tracts with increased MD, AD, or RD values in DM2 patients compared to DM1. Our results indicate diffuse disintegration of white matter pathways in DM patients, especially in the DM1 group. The damage to all types of fibres (association, commissural, and projection) may explain the diversity of clinical symptoms, which were more severe in the DM1 group of patients than in the DM2 group. DTI in patients with DM may help us to understand the neural mechanisms underlying brain involvement during the disease. In future, it may help to identify biomarkers for disease progression and treatment response.

Molecular mechanisms underlying hyperglycemia associated cognitive decline.

Diabetes mellitus (DM) is a metabolic disease characterized by chronic hyperglycemia. DM can lead to a number of secondary complications affecting multiple organs in the body including the eyes, kidney, heart, and brain. The most common effect of hyperglycemia on the brain is cognitive decline. It has been estimated that 20-70% of people with DM have cognitive deficits. High blood sugar affects key brain areas involved in learning, memory, and spatial navigation, and the structural complexity of the brain has made it prone to a variety of pathological disorders, including T2DM. Studies have reported that cognitive decline can occur in people with diabetes, which could go undetected for several years. Moreover, studies on brain imaging suggest extensive effects on different brain regions in patients with T2D. It remains unclear whether diabetes-associated cognitive decline is a consequence of hyperglycemia or a complication that co-occurs with T2D. The exact mechanism underlying cognitive impairment in diabetes is complex; however, impaired glucose metabolism and abnormal insulin function are thought to play important roles. In this review, we have tried to summarize the effect of hyperglycemia on the brain structure and functions, along with the potential mechanisms underlying T2DM-associated cognitive decline.

The Neuropsychological Mechanisms of Treatment of Bipolar Disorder and Borderline Personality Disorder: Activation Likelihood Estimation Meta-Analysis of Brain Imaging Research.

Objective: To explore the alteration of brain regions after treatments for bipolar disorder (BD) and borderline personality disorder (BPD) in order to discover the underlying neural mechanisms of therapies.Data Sources: An electronic search of the PubMed, Embase, Cochrane Library, and Web of Science databases from inception until June 2021 was conducted.Study Selection: Articles reporting the results of changes in brain activation after treatment, to assess the effects of therapy relative to a before-treatment condition, were included. A total of 1,592 records were retrieved, with 34 studies ultimately included.Data Extraction: Activation coordinates were extracted from each study. We used activation likelihood estimation meta-analysis to evaluate the similarities and differences in the activation of different brain regions in patients with BD and BPD after treatment with psychotherapy and drug therapy.Results: Most brain regions with abnormal activation were improved after treatments for BD and BPD. The brain activity changes produced by psychotherapy were mostly in the frontal areas, while drug therapy primarily impacted the limbic areas. In BD, treatments were associated with activation alterations in the inferior frontal gyrus, superior temporal gyrus, and cingulate gyrus, while in BPD, treatments were associated with activation alterations in the supramarginal gyrus, middle frontal gyrus, and parahippocampal gyrus.Conclusions: These results suggest that drug therapy might have a bottom-up effect, while psychotherapy might have a top-down effect. This study may contribute to the clinical prediction of treatment efficacy in BD and BPD and to the identification of more accurate neuroimaging biomarkers for treatment of the two disorders.

Conclusions of the SIGNAL study in Huntington and implications for treatment of other slowly progressive neurodegenerative diseases.

Conclusions of the SIGNAL study in Huntington and implications for treatment of other slowly progressive neurodegenerative diseases.

Alterations in the Expression of the Genes Responsible for the Synthesis of Heparan Sulfate in Brains With Alzheimer Disease.

The saccharide chains of heparan sulfate appear to be involved in several aspects Alzheimer disease (AD) pathogenesis. Their structural complexity is due to the expression of different isoenzymes. We studied the differential transcription of heparan sulfate chain biosynthesis in AD brains, analyzing different brain regions in patients with different extents of AD pathology. The transcriptomic study was performed by RT-PCR using samples of amygdala, anterior hippocampus, posterior hippocampus, claustrum, calcarine fissure, globus pallidus and cerebellum from patients with mild, moderate, or severe AD, as well as healthy individuals. Certain heparan sulfate epitopes were also detected by immunohistochemistry. Several genes, across all stages of heparan sulfate synthesis, showed altered transcription in different brain regions of AD patients. The numbers of alterations were greater in in moderate versus mild AD patients. In severe patients, there were fewer alterations in genes related to early stages of biosynthesis, and overexpression of genes involved in late stages. The alterations correlated with progressive brain atrophy, although alterations were more common in the cerebellum. Detection of some heparan sulfate epitopes by immunohistochemistry was consistent with previous studies. In conclusion, transcriptional alterations in the biosynthetic genes of heparan sulfate depend on the brain region and the degree of AD pathology.

Abnormal Regional Spontaneous Neural Activity in Nonarteritic Anterior Ischemic Optic Neuropathy: A Resting-State Functional MRI Study.

Objective To explore altered regional neuronal activity in patients with nonarteritic anterior ischemic optic neuropathy (NAION) and its correlation with clinical performances using the regional homogeneity (ReHo) method, which is based on resting-state functional magnetic resonance imaging (fMRI). Method Thirty-one patients with NAION (20 males, 11 females) and 31 age- and sex-matched normal controls (NCs) (20 males, 11 females) were enrolled in the study. All patients underwent ophthalmic examination, including eyesight, intraocular pressure measurement, optimal coherence tomography (OCT), visual field analysis, and fMRI scans. After ReHo was calculated, we investigated group differences in results between the patients and NCs. We analyzed the relationship between ReHo values for different brain regions in patients with NAION and intraocular pressure, visual field analysis, and OCT. A receiver operating characteristic (ROC) curve was used to assess the diagnostic ability of the ReHo method. Results Compared with NCs, patients with NAION exhibited higher ReHo values in the left middle frontal gyrus, left middle cingulate gyrus, left superior temporal gyrus, and left inferior parietal lobule. Additionally, they exhibited lower ReHo values in the right lingual gyrus, left putamen/lentiform nucleus, and left superior parietal lobule. ReHo values in the left superior parietal lobule were negatively correlated with right retinal nerve fiber layer values (r = −0.462, P = 0.01). The area under the ROC curve for each brain region indicated that the ReHo method is a credible means of diagnosing patient with NAION. Conclusion NAION was primarily associated with dysfunction in the default mode network, which may reflect its underlying neural mechanisms.

Abnormal dynamic functional connectivity density in patients with generalized anxiety disorder

BackgroundNumerous studies have revealed the abnormal static functional connectivity (FC) among different brain regions in patients with generalized anxiety disorder (GAD). However, little is known about the dynamic changes of FC in patients with GAD. MethodsThis study investigated the whole-brain dynamic changes of FC in patients with GAD by combining global FC density (FCD) and sliding window correlation analyses. The standard deviation of dynamic FCD (dFCD) was calculated to evaluate its temporal variability along time. Support vector regression was then employed to predict the symptom severity of patients based on abnormal dynamic connectivity patterns. ResultsThe abnormal dFCD variability between 81 GAD patients and 80 healthy controls showed that the patients had higher dFCD variability in the bilateral dorsomedial prefrontal cortex (dmPFC) and left hippocampus while lower dFCD variability in the right postcentral gyrus. The abnormal dFCD variability of the left dmPFC is an important feature for anxiety prediction. LimitationsThe selection of sliding window length remains controversial, and most of our patients have been treated with medications. Future studies are expected to rule out the potential confounding effects from applying different parameters of the sliding window and recruiting large samples of medication-free patients. ConclusionThe altered patterns of time-varying brain connectivity in the frontolimbic and sensorimotor areas may reflect abnormal dynamic neural communication between these regions and other regions of the brain, which may deepen our understanding of the disease.

Altered spontaneous brain activity patterns in patients with retinal vein occlusion indicated by the amplitude of low-frequency fluctuation: A functional magnetic resonance imaging study.

The aim of the present study was to explore the amplitude of low-frequency fluctuations (ALFF; a measurement of spontaneous brain activity) in different brain regions of patients with retinal vein occlusion (RVO) and its association with vision changes measurements. A total of 24 RVO patients (12 males and 12 females) and 24 healthy controls (HCs, 12 males and 12 females) were recruited, and they were closely matched regarding age, gender and education level (classified according to nine-year compulsory education in China and higher education, all including primary school, junior school, high school and university). ALFF values of different brain regions were gathered and analyzed, and statistical analysis software was used to explore the correlations between the average ALFF signals and clinical features. The ability of ALFF values to distinguish between subjects with RVO and HCs was analyzed by receiver operating characteristic (ROC) curves. The results indicated that the subjects from the RVO group had higher ALFF values than the HCs in the posterior lobe of the left cerebellum, inferior temporal gyrus, cerebellar anterior lobe, right cerebellum posterior/anterior lobe, and lower ALFF values in the medial frontal gyrus, right precuneus, left middle frontal gyrus, right angular gyrus and right superior frontal gyrus. The ROC curve analysis of each brain region indicated that the accuracy of the area under the ROC curves regarding the prediction of RVO was excellent. The best-corrected visual acuity (VA) in the left eye was positively correlated with the ALFF value of the right precuneus (r=0.767, P=0.004) and the best-corrected VA in the right eye was positively correlated with the ALFF value of the left middle frontal gyrus (r=0.935, P<0.001). The central subfield retinal thickness in the left eye was negatively correlated with the ALFF value of the right precuneus (r=−0.895; P<0.001). The duration of RVO in the right eye was positively correlated with the ALFF value of the left middle frontal gyrus (r=0.868; P<0.001). In conclusion, the present results indicate that RVO is associated with dysfunction of diverse brain regions, including language- and movement-associated areas, which may reflect the underlying pathogenic mechanisms of RVO (trial registry no. CDYFY-LL-2017025).

Quantitative determination of concordance in localizing epileptic focus by component-based EEG-fMRI

Background and objectiveAccurate seizure onset zone (SOZ) localization is an essential step in pre-surgical assessment of patients with refractory focal epilepsy. Complex pathophysiology of epileptic cerebral structures, seizure types and frequencies have not been considered as influential features for accurate identification of SOZ using EEG-fMRI. There is a crucial need to quantitatively measure concordance between presumed SOZ and IED-related BOLD response in different brain regions to improve SOZ delineation. MethodsA novel component-based EEG-fMRI approach is proposed to measure physical distance between BOLD clusters and selected component dipole location using patient-specific high resolution anatomical images. The method is applied on 18 patients with refractory focal epilepsy to localize epileptic focus and determine concordance quantitatively and compare between maximum BOLD cluster with identified component dipole. To measure concordance, distance from a voxel with maximal z-score of maximum BOLD to center of extracted component dipole is measured. ResultsBOLD clusters to spikes distances for concordant (<25 mm), partially concordant (25–50 mm), and discordant (>50 mm) groups were significantly different (p < 0.0001). The results showed full concordance in 17 IED types (17.85 ± 4.69 mm), partial concordance in 4 (36.47 ± 8.84 mm), and nodiscordance, which is a significant rise compared to the existing literature. The proposed method is premised on the cross-correlation between the spike template outside the scanner and the highly-ranked extracted components. It successfully surpasses the limitations of conventional EEG-fMRI studies which are largely dependent on inside-scanner spikes. More significantly, the proposed method improves localization accuracy to 97% which marks a dramatic rise compared to conventional works. ConclusionsThis study demonstrated that BOLD changes were related to epileptic spikes in different brain regions in patients with refractory focal epilepsy. In a systematic quantitative approach, concordance levels based on the distance between center of maximum BOLD cluster and dipole were determined by component-based EEG-fMRI method. Therefore, component-based EEG-fMRI can be considered as a reliable predictor of SOZ in patients with focal epilepsy and included as part of clinical evaluation for patients with medically resistant epilepsy.

Altered Spontaneous Brain Activity in Patients with Classical Trigeminal Neuralgia Using Regional Homogeneity: A Resting-State Functional MRI Study.

Neuroimaging studies have shown that patients with pain-related conditions have altered neuronal activity and structural functions. The purpose of this study was to investigate whether patients with classical trigeminal neuralgia (CTN) exhibit changes in corresponding neuronal activity via analysis of neuronal activity regional homogeneity (ReHo). A total of 28 patients presenting with sore eyes (12 men and 16 women) were matched with 28 healthy controls (12 men and 16 women). All participants underwent functional magnetic resonance imaging (fMRI). This ReHo method was used to assess the consistency of changes in neural activity in various brain regions. The receiver operating characteristic (ROC) curve was applied to differentiate ReHo values of patients with CTN from ReHo values of healthy controls. Pearson's correlation analysis was applied to evaluate the correlation between ReHo values of different brain regions of patients with CTN and clinical manifestations. Compared with healthy controls, patients with CTN were found to have increased ReHo values in the inferior cerebellum bilaterally, right inferior temporal gyrus, right middle occipital gyrus, right fusiform gyrus, right superior frontal gyrus, and right precentral gyrus. ROC curve analysis of each brain region revealed near-perfect accuracy regarding the area under the curve. However, no correlation between ReHo values and clinical manifestations in patients with CTN was found. CTN is associated with altered neuronal networks in different areas of the brain. ReHo values all possess different degrees of change, implying that CTN has a certain impact on cerebral function.

Resting-state fMRI study of patients with fragile X syndrome

The study aimed to assess the neural activity of different brain regions in patients with fragile X syndrome (FXS) and the healthy volunteers by resting-state functional magnetic resonance imaging (fMRI) on a 1.5 T MRI Achieva scanner (Philips). Results: The fMRI study showed a DMN of brain function in patients with FXS, as well as in the healthy volunteers. Furthermore, it was found that a default mode network of the brain in patients with FXS and healthy volunteers does not have statistically significant differences (p>0.05), which may indicate that the basal activity of neurons in patients with FXS is not reduced. In addition, we have found a significant (p<0.001) increase in the FC within the right inferior parietal and right angular gyrus in the resting state in patients with FXS. Conclusion: New data of functional status of the brain in patients with FXS were received. The significant increase in the resting state functional connectivity within the right inferior parietal and right angular gyrus (p<0.001) in patients with FXS was found.

Investigating the Role of the Endocannabinoid System in Early Psychosis

Accumulating evidence suggests that dysfunction within the endocannabinoid (eCB) system may play a role in psychosis. However, little is understood about how this may be related to the neurocognitive abnormalities and symptoms of psychosis. In this paper, we summarize some of the evidence supporting the role of eCB system in psychosis, as well as the current understanding of the neurocognitive underpinnings of psychosis. We particularly focus on neuroimaging evidence pertaining to alteration in the functional integration between different brain regions in patients with psychosis, and then relate this to evidence from neuroimaging studies of the effects of cannabis and its main ingredients, such as delta-9-tetrahydrocannainol and cannabidiol. Specifically, we explore this in the context of the hypothesis that psychosis is a disorder of dysconnectivity between different brain regions, focusing particularly on three large scale functional networks (the default mode, central executive, and salience networks), alterations in which have been implicated in psychosis, and we discuss the gaps in this research thus far. Finally, we propose that an approach to investigating the role of the eCB system in psychosis may be to employ a pharmacological cannabinoid challenge paradigm to examine how experimental perturbation of the eCB system may be related to abnormalities in the brain networks implicated in psychosis. We discuss challenges associated with this approach, and suggest safe and practical options to overcome the main issues involved with such an experimental approach. Studies employing such an approach have the potential of offering insight into the neurocognitive mechanisms underlying psychosis, and identifying novel therapeutic targets.

Alterations of cerebral white matter structure in psychosis and their clinical correlations: a systematic review of Diffusion Tensor Imaging studies.

Schizophrenia is a common, severe and chronically disabling mental illness. Most of MRI studies in schizophrenia suggest the involvement of white matter (WM) pathology in multiple cerebral regions in the neurobiology of this condition. White matter fiber tracts connecting numerous cortical regions have been the focus of a number of studies using a magnetic resonance technique called “Diffusion Tensor Imaging” (DTI). A literature search of published DTI studies was conducted using the major database National Centre for Biotechnology information (NCBI) PubMed (MEDLINE). Our review covers 95 published papers. We summarise the main DTI findings involving the different brain regions in patients affected by or at high-risk for psychosis; we discuss clinical implications of these white matter disruptions and the limitations of current studies, listing the potential confounds and suggesting potential future research directions.

Systematic analysis of microarray datasets to identify Parkinson's disease‑associated pathways and genes.

In order to investigate commonly disturbed genes and pathways in various brain regions of patients with Parkinson's disease (PD), microarray datasets from previous studies were collected and systematically analyzed. Different normalization methods were applied to microarray datasets from different platforms. A strategy combining gene co-expression networks and clinical information was adopted, using weighted gene co-expression network analysis (WGCNA) to screen for commonly disturbed genes in different brain regions of patients with PD. Functional enrichment analysis of commonly disturbed genes was performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). Co-pathway relationships were identified with Pearson's correlation coefficient tests and a hypergeometric distribution-based test. Common genes in pathway pairs were selected out and regarded as risk genes. A total of 17 microarray datasets from 7 platforms were retained for further analysis. Five gene coexpression modules were identified, containing 9,745, 736, 233, 101 and 93 genes, respectively. One module was significantly correlated with PD samples and thus the 736 genes it contained were considered to be candidate PD-associated genes. Functional enrichment analysis demonstrated that these genes were implicated in oxidative phosphorylation and PD. A total of 44 pathway pairs and 52 risk genes were revealed, and a risk gene pathway relationship network was constructed. Eight modules were identified and were revealed to be associated with PD, cancers and metabolism. A number of disturbed pathways and risk genes were unveiled in PD, and these findings may help advance understanding of PD pathogenesis.

CHARACTERIZATION OF THE POSTSYNAPTIC PROTEIN NEUROGRANIN IN DIFFERENT BRAIN REGIONS IN PATIENTS WITH FAMILIAL ALZHEIMER’S DISEASE, ALZHEIMER'S DISEASE, PATHOLOGICAL AGING AND HEALTHY CONTROLS

CHARACTERIZATION OF THE POSTSYNAPTIC PROTEIN NEUROGRANIN IN DIFFERENT BRAIN REGIONS IN PATIENTS WITH FAMILIAL ALZHEIMER’S DISEASE, ALZHEIMER'S DISEASE, PATHOLOGICAL AGING AND HEALTHY CONTROLS

MRI appearances of aquaporin and its effect in different brain regions of patients with Parkinson's disease

Objective To investigate MRI appearances of aquaporin(AQP) and its effect in different brain regions of patients with Parkinson's disease(PD). Methods A prospective study was carried out in 33 PD patients(PD group) and 23 gender- and age-matched healthy controls(control group). Clinical data of PD patients were collected.The aquaporin imaging of diffusion-weighted magnetic resonance imaging(MR-DWI) with multiple b-values in different brain regions were performed to detect the apparent diffusion coefficient(AQP-ADC) values of aquaporin.The PD patients were assessed and graded by modified Hoehn-Yahr grading, then the AQP-ADC values of control group, mild PD group, moderate and severe PD group were analyzed using one-way analysis of variance.The correlation analysis was carried out to detect the relationship between AQP-ADC values in different brain regions and Hoehn-Yahr grading of PD patients. Results Compared with control group, mild PD group had significantly higher AQP-ADC values in red nucleus(RN) and globus pallidus(GP) ((0.24±0.04) vs (0.21±0.04), ( 0.21±0.04) vs (0.16±0.04); both P 0.05); and there was also no significant difference in substantianigra(SN), putamen(Pu) and thalamus(THA) among control group, mild PD group and moderate and severe PD group(P>0.05). The correlation analysis showed that there were negative correlations between the AQP-ADC values in RN and GP and Hoehn-Yahr grading(r=-0.479 and -0.395, P 0.05). Conclusion The AQP-ADC values are increased in RN and GP of mild PD patients, and decreased in moderate and severe PD patients, while there is no significant change in SN, Pu and THA of the two groups, suggesting that the expression of AQP in different brain regions may be related to the severity and pathological stage of PD. Key words: Parkinson's disease; Aquaporin; Molecular imaging; Diffusion-weighted magnetic resonance imaging

Anomalous gray matter structural networks in patients with hepatitis B virus-related cirrhosis without overt hepatic encephalopathy.

Background and PurposeIncreasing evidence suggests that cirrhosis may affect the connectivity among different brain regions in patients before overt hepatic encephalopathy (OHE) occurs. However, there has been no study investigating the structural reorganization of these altered connections at the network level. The primary focus of this study was to investigate the abnormal topological organization of the structural network in patients with hepatitis B virus-related cirrhosis (HBV-RC) without OHE using structural MRI.MethodsUsing graph theoretical analysis, we compared the global and regional topological properties of gray matter structural networks between 28 patients with HBV-RC without OHE and 30 age-, sex- and education-matched healthy controls. The structural correlation networks were constructed for the two groups based on measures of gray matter volume.ResultsThe brain network of the HBV-RC group exhibited a significant decrease in the clustering coefficient and reduced small-worldness at the global level across a range of network densities. Regionally, brain areas with altered nodal degree/betweenness centrality were observed predominantly in association cortices (frontal and temporal regions) (p < 0.05, uncorrected), including a significantly decreased nodal degree in the inferior temporal gyrus (p < 0.001, uncorrected). Furthermore, the HBV-RC group exhibited a loss of association hubs and the emergence of an increased number of non-association hubs compared with the healthy controls.ConclusionThe results of this large-scale gray matter structural network study suggest reduced topological organization efficiency in patients with HBV-RC without OHE. Our findings provide new insight concerning the mechanisms of neurobiological reorganization in the HBV-RC brain from a network perspective.

Effects of Electroacupuncture on Depression and the Production of Glial Cell Line–Derived Neurotrophic Factor Compared with Fluoxetine: A Randomized Controlled Pilot Study

Postmortem studies indicate that the number and density of glial cells are reduced in different brain regions of patients with depression. Glial cell line-derived neurotrophic factor (GDNF) plays an important role in the pathogenesis of depressive disorder (DD) and might be a biomarker for damage to nerve cells. In this study, we compared the therapeutic effects of electroacupuncture (EA) and fluoxetine, a serotonin reuptake inhibitor, on DD patients, focusing on the serum level of GDNF. This was a prospective, randomized clinical trial. Seventy-five patients with DD from the Department of Acupuncture, Beijing Hospital of Traditional Chinese Medicine, were recruited. Twenty patients were treated with acupuncture for 6 weeks on the acupoints of Baihui (DU20) and Zusanli (ST36). Sixteen patients were treated with acupuncture for 6 weeks on the acupoints of Taichong (LR3), Sanyinjiao (SP6), Neiguan (PC6), and Shenmen (HT7), and constituted the electroacupuncture control group. The patients received acupuncture treatment five times per week. Twenty-five patients were treated with oral fluoxetine (20 mg/day) for 6 weeks. All subjects were evaluated by the Hamilton Depression Rating Scale at four time points (0 [baseline], 2, 4, and 6 weeks after treatment). Serum GDNF was quantified in duplicate by enzyme-linked immunosorbent assay (ELISA). EA and fluoxetine had similar curative effects on DD patients. EA had a faster onset of action, better response rate, and better improvement rate than fluoxetine. Both fluoxetine and EA treatment restored the normal concentration of GDNF in the serum of DD patients. EA treatment for depression is as effective as a recommended dose of fluoxetine. However, EA demonstrates an advantage in the regulation of the production of GDNF compared with fluoxetine.

Sodium Phenylbutyrate Enhances Astrocytic Neurotrophin Synthesis via Protein Kinase C (PKC)-mediated Activation of cAMP-response Element-binding Protein (CREB): IMPLICATIONS FOR ALZHEIMER DISEASE THERAPY

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are believed to be genuine molecular mediators of neuronal growth and homeostatic synapse activity. However, levels of these neurotrophic factors decrease in different brain regions of patients with Alzheimer disease (AD). Induction of astrocytic neurotrophin synthesis is a poorly understood phenomenon but represents a plausible therapeutic target because neuronal neurotrophin production is aberrant in AD and other neurodegenerative diseases. Here, we delineate that sodium phenylbutyrate (NaPB), a Food and Drug Administration-approved oral medication for hyperammonemia, induces astrocytic BDNF and NT-3 expression via the protein kinase C (PKC)-cAMP-response element-binding protein (CREB) pathway. NaPB treatment increased the direct association between PKC and CREB followed by phosphorylation of CREB (Ser(133)) and induction of DNA binding and transcriptional activation of CREB. Up-regulation of markers for synaptic function and plasticity in cultured hippocampal neurons by NaPB-treated astroglial supernatants and its abrogation by anti-TrkB blocking antibody suggest that NaPB-induced astroglial neurotrophins are functionally active. Moreover, oral administration of NaPB increased the levels of BDNF and NT-3 in the CNS and improved spatial learning and memory in a mouse model of AD. Our results highlight a novel neurotrophic property of NaPB that may be used to augment neurotrophins in the CNS and improve synaptic function in disease states such as AD.