scholarly journals Microarray analysis reveals distinctive signaling between the bed nucleus of the stria terminalis, nucleus accumbens, and dorsal striatum

2008 ◽  
Vol 32 (3) ◽  
pp. 283-298 ◽  
Author(s):  
Christopher M. Olsen ◽  
Yong Huang ◽  
Shirlean Goodwin ◽  
Daniel C. Ciobanu ◽  
Lu Lu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synaptic Plasticity ◽  
Nucleus Accumbens ◽  
Signaling Pathways ◽  
Microarray Analysis ◽  
Dorsal Striatum ◽  
Brain Regions ◽  
Stria Terminalis ◽  
Bed Nucleus ◽  
Insight Into

To identify distinct transcriptional patterns between the major subcortical dopamine targets commonly studied in addiction we studied differences in gene expression between the bed nucleus of the stria terminalis (BNST), nucleus accumbens (NAc), and dorsal striatum (dStr) using microarray analysis. We first tested for differences in expression of genes encoding transcripts for common neurotransmitter systems as well as calcium binding proteins routinely used in neuroanatomical delineation of brain regions. This a priori method revealed differential expression of corticotropin releasing hormone ( Crh), the GABA transporter ( Slc6a1), and prodynorphin ( Pdyn) mRNAs as well as several others. Using a gene ontology tool, functional scoring analysis, and Ingenuity Pathway Analysis, we further identified several physiological pathways that were distinct among these brain regions. These two different analyses both identified calcium signaling, G-coupled protein receptor signaling, and adenylate cyclase-related signaling as significantly different among the BNST, NAc, and dStr. These types of signaling pathways play important roles in, amongst other things, synaptic plasticity. Investigation of differential gene expression revealed several instances that may provide insight into reported differences in synaptic plasticity between these brain regions. The results support other studies suggesting that crucial pathways involved in neurotransmission are distinct among the BNST, NAc, and dStr and provide insight into the potential use of pharmacological agents that may target region-specific signaling pathways. Furthermore, these studies provide a framework for future mouse-mouse comparisons of transcriptional profiles after behavioral/pharmacological manipulation.

scholarly journals S205. A TRANSLATIONAL HOMER 1A-BASED NETWORK APPROACH: IMAGING HOW HALOPERIDOL MODULATES GLUTAMATE SYSTEM FUNCTIONAL CONNECTIVITY

2020 ◽  
Vol 46 (Supplement_1) ◽  
pp. S116-S117
Author(s):  
Licia Vellucci ◽  
Felice Iasevoli ◽  
Elisabetta Filomena Buonaguro ◽  
Gianmarco Latte ◽  
Carmine Tomasetti ◽  
...  
Keyword(s):  
Gene Expression ◽  
Synaptic Plasticity ◽  
Nucleus Accumbens ◽  
Side Effects ◽  
Functional Connectivity ◽  
Acute Administration ◽  
Functional Interaction ◽  
Treatment Groups ◽  
Student’S T ◽  
Glutamate System

Abstract Background Schizophrenia has been conceptualized both as synaptic plasticity and a functional connectivity disorder. Data on brain connectivity can be rendered in the form of network models. In our study we want to evaluate a particular kind of the structural and functional interaction between region of interest (ROI) relevant to schizophrenia pathophysiology: we evaluated the expression of Immediate Early Gene (IEG), Homer1a (H1a), in the different ROI and its functional interaction after Haloperidol (antipsychotic drug) acute administration. H1a is an IEG expressed in an activity-dependent manner, coding for a protein involved in the activity-induced reorganization of glutamatergic synapses. Methods Sprague-Dawley rats were randomly assigned to two treatment groups (n=23), receiving vehicle (NaCl 0.9%; VEH) or haloperidol 0.8 mg/kg (HAL) i.p. injection. H1a induction was evaluated using in situ hybridization. Signal intensity analysis was performed in 34 ROIs in the cortex, in the caudate-putamen and the nucleus accumbens. Student’s t-test was used to detect treatment effects. A signal correlation analysis was performed, computing all possible pairwise Pearson correlations among ROIs separately in the two groups. Using significant correlations, two networks were created for HAL and VEH groups, and their network, node, and edge properties were assessed. Results Bonferroni-corrected Student’s t-tests revealed statistically significant differences between the two treatment groups. Haloperidol significantly induced Homer1a gene expression compared to vehicle in all ROIs of the striatum (dmCP: p<.0001, t=9.089, df=44; dlCP: p<.0001, t=10.684, df=44; vlCP: p<.0001, t=10.870, df=44; vmCP: p<.0001, t=9.760, df=44; AcCo: p<.0001, t=8,573, df= 44; AcSh: p<.0001, t=6.615, df=44), a result that is consistent with our previous observations. No significant statistical differences were detected among cortical ROIs explored. Correlations between dmCP-AcSh, dlCP-AcSh, vlCP-AcCo, vlCP-AcSh and vmCP-AcSh were significantly different between the VEH and the HAL group (p<.01); correlations between I-vlCP and dlCP-AcCo were also significantly different between the two treatment groups (p<.05); the I-dlCP and I-vmCP showed a trend towards significance. Discussion Haloperidol acute administration led to a modification of the gene expression pattern in the brain regions considered herein, and consequently to differential functional connectivity. The observed disruption in the functional correlations of the nucleus accumbens may play a role in the affective, motivational and emotional consequences of haloperidol administration, with the loss of functional correlations with the lateral subregions of the caudate-putamen being potentially more relevant to the motor side-effects of haloperidol. These functional connectivity changes are potentially related to neural activity and synaptic plasticity within the glutamate system and may play a role in antipsychotic therapeutic and side effects. As far as we know, this is the first network analysis study on after haloperidol acute treatment of a gene deeply correlated to dendritic spine architecture.

scholarly journals Synaptic Plasticity and its Modulation by Alcohol

2020 ◽  
Vol 6 (1) ◽  
pp. 103-111 ◽  
Author(s):  
Yosef Avchalumov ◽  
Chitra D. Mandyam
Keyword(s):  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Dorsal Striatum ◽  
Long Term Potentiation ◽  
Brain Regions ◽  
Public Health Issue ◽  
Cellular Mechanisms ◽  
Brain Disorder ◽  
The Brain

Alcohol is one of the oldest pharmacological agents used for its sedative/hypnotic effects, and alcohol abuse and alcohol use disorder (AUD) continues to be major public health issue. AUD is strongly indicated to be a brain disorder, and the molecular and cellular mechanism/s by which alcohol produces its effects in the brain are only now beginning to be understood. In the brain, synaptic plasticity or strengthening or weakening of synapses, can be enhanced or reduced by a variety of stimulation paradigms. Synaptic plasticity is thought to be responsible for important processes involved in the cellular mechanisms of learning and memory. Long-term potentiation (LTP) is a form of synaptic plasticity, and occurs via N-methyl-D-aspartate type glutamate receptor (NMDAR or GluN) dependent and independent mechanisms. In particular, NMDARs are a major target of alcohol, and are implicated in different types of learning and memory. Therefore, understanding the effect of alcohol on synaptic plasticity and transmission mediated by glutamatergic signaling is becoming important, and this will help us understand the significant contribution of the glutamatergic system in AUD. In the first part of this review, we will briefly discuss the mechanisms underlying long term synaptic plasticity in the dorsal striatum, neocortex and the hippocampus. In the second part we will discuss how alcohol (ethanol, EtOH) can modulate long term synaptic plasticity in these three brain regions, mainly from neurophysiological and electrophysiological studies. Taken together, understanding the mechanism(s) underlying alcohol induced changes in brain function may lead to the development of more effective therapeutic agents to reduce AUDs.

scholarly journals Epigenetic Mechanisms Involved in HCV-Induced Hepatocellular Carcinoma (HCC)

2021 ◽  
Vol 11 ◽  
Author(s):  
Pin Zhao ◽  
Samiullah Malik ◽  
Shaojun Xing
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Signaling Pathways ◽  
Hcv Infection ◽  
Specific Gene ◽  
Epigenetic Alterations ◽  
Chronic Hcv Infection ◽  
Mechanisms Of Carcinogenesis ◽  
Chronic Hcv ◽  
Insight Into

Hepatocellular carcinoma (HCC), is the third leading cause of cancer-related deaths, which is largely caused by virus infection. About 80% of the virus-infected people develop a chronic infection that eventually leads to liver cirrhosis and hepatocellular carcinoma (HCC). With approximately 71 million HCV chronic infected patients worldwide, they still have a high risk of HCC in the near future. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches. Hepatitis C virus (HCV) infection largely causes hepatocellular carcinoma (HCC) worldwide with 3 to 4 million newly infected cases diagnosed each year. It is urgent to explore its underlying molecular mechanisms for therapeutic treatment and biomarker discovery. However, the mechanisms of carcinogenesis in chronic HCV infection have not been still fully understood, which involve a complex epigenetic regulation and cellular signaling pathways. Here, we summarize 18 specific gene targets and different signaling pathways involved in recent findings. With these epigenetic alterations requiring histone modifications and DNA hyper or hypo-methylation of these specific genes, the dysregulation of gene expression is also associated with different signaling pathways for the HCV life cycle and HCC. These findings provide a novel insight into a correlation between HCV infection and HCC tumorigenesis, as well as potentially preventable approaches.

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