Modulation of the glutamatergic transmission by Dopamine: a focus on Parkinson, Huntington and Addiction diseases.

Dopamine (DA) plays a major role in motor and cognitive functions as well as in reward processing by regulating glutamatergic inputs. In particular in the striatum the release of DA rapidly influences synaptic transmission modulating both AMPA and NMDA receptors. Several neurodegenerative and neuropsychiatric disorders, including Parkinson, Huntington and addiction-related diseases, manifest a dysregulation of glutamate and DA signaling. Here, we will focus our attention on the mechanisms underlying the modulation of the glutamatergic transmission by DA in striatal circuits

Time-Dependent Probability of Exceeding a Target Level of Recovery

The resilience of a system is generally defined in terms of its ability to withstand external perturbations, adapt, and rapidly recover. This paper introduces a probabilistic formulation to predict the recovery process of a system given past recovery data and to estimate the probability of reaching or exceeding a target value of functionality at any time. A Bayesian inference is used to capture the changes over time of model parameters as recovery data become available during the work progress. The proposed formulation is general and can be applied to continuous recovery processes such as those of economic or natural systems, as well as to discrete recovery processes typical of engineering systems. As an illustration of the proposed formulation, two examples are provided. The paper models the recovery of a reinforced concrete bridge following seismic damage, as well as the population relocation after the occurrence of a seismic event when no data on the duration of the recovery are available a priori

From cell lines to pluripotent Stem Cells for Modelling Parkinson's Disease

Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by loss of dopaminergic (DAergic) neurons in the substantia nigra that contributes to the main motor symptoms of the disease. At present, even if several advancements have been done in the last decades, the molecular and cellular mechanisms involved in the pathogenesis are far to be fully understood. Accordingly, the establishment of reliable in vitro experimental models to investigate the early events of the pathogenesis represents a key issue in the field. However, to mimic and reproduce in vitro the complex neuronal circuitry involved in PD-associated degeneration of DAergic neurons still remains a highly challenging issue. Here we will review the in vitro PD models used in the last 25 years of research, ranging from cell lines, primary rat or mice neuronal cultures to the more recent use of human induced pluripotent stem cells (hiPSCs) and, finally, the development of 3D midbrain organoids

ANALISIS FAKTOR-FAKTOR YANG MEMPENGARUHI PRODUKSI IKAN BANDENG DI KOTA BANDA ACEH

ABSTRAKPenelitian ini bertujuan untuk mengetahui faktor-faktor yang mempengaruhi produksi ikan bandeng di Kota Banda Aceh. Penelitian ini dilakukan menggunakan metode survey dan pengambilan sampelnya dengan teknik sampel acak sederhana Simple Random Sampling.Lokasi penelitian dilakukan di Kota Banda Aceh, yaitu Kecamatan Syiah Kuala, Meuraxa, Kuta Alam, dan Kuta Raja. Waktu Penelitian dilaksanakan pada bulan Oktober 2013 sampai dengan Juli 2014. Model yang digunakan dalam penelitian ini adalah menggunakan model analisis kuantitatif untuk mengetahui Faktor-faktor yang mempengaruhi produksi ikan bandeng di Kota Banda Aceh yaitu tenaga kerja, luas tambak, jumlah nener, dan penggunaan pupuk..Untuk menguji hubungan antara variabel faktor-faktor yang mempengaruhi produksi ikan bandeng di Kota Banda Aceh, digunakan uji statistik dengan menggunakan uji T, F, dan R2.Hasil penelitian ini dapat disimpulkan bahwa secara serempak faktor , tenaga kerja, luas tambak, jumlah nener, dan jumlah pupuk berpengaruh nyata terhadap produksi ikan bandeng di Kota Banda Aceh. Secara parsial faktor jumlah nener berpengaruh nyata terhadap produksi ikan bandeng di Kota Banda Aceh. Sedangkan faktor tenaga kerja, luas tambak dan jumlah pupuk tidak berpengaruh nyata terhadap produksi ikan bandeng di Kota Banda Aceh.Kata Kunci: Ikan bandeng, analisis produksiABSTRACTThis research aims to determine the factors that affect fish production in the city of Banda Aceh. This research was conducted using a survey method and sampling with simple random sampling techniques.Location of the research conducted in the city of Banda Aceh , the District Syiah KuaLa, Meuraxa, Kuta Alam, and Kuta Raja. Time research conducted in October 2013 to July 2014 model used in this research was to use quantitative analysis model to determine the factors that affect milkfish production in Banda Aceh, namely labor, large farms, the amount of milkfish, and use of fertilizers.For Examine the relationship between the variable factors that affect milkfish production in Banda Aceh, used statistical tests using T test, F, and R2.The results of this research it can be concluded that the factors simultaneously, labor, large ponds, milkfish amount, and the amount of fertilizer significantly affect milkfish production in the city of Banda Aceh. Partially factors significantly affect the amount of milkfish fry production of milkfish in Banda Aceh. While the labor factor, vast farms and the amount of fertilizer had no significant effect on the production of milkfish in Banda Aceh .Keywords: Milkfish, production analysisBanda Ace

Elongation factor-2 phosphorylation in dendrites and the regulation of dendritic mRNA translation in neurons

Neuronal activity results in long lasting changes in synaptic structure and function by regulating mRNA translation in dendrites. These activity dependent events yield the synthesis of proteins known to be important for synaptic modifications and diverse forms of synaptic plasticity. Worthy of note, there is accumulating evidence that the eukaryotic Elongation Factor 2 Kinase (eEF2K)/eukaryotic Elongation Factor 2 (eEF2) pathway may be strongly involved in this process. Upon activation, eEF2K phosphorylates and thereby inhibits eEF2, resulting in a dramatic reduction of mRNA translation. eEF2K is activated by elevated levels of calcium and binding of Calmodulin (CaM), hence its alternative name calcium/CaM-dependent protein kinase III (CaMKIII). In dendrites, this process depends on glutamate signaling and N-methyl-D-aspartate receptor (NMDAR) activation. Interestingly, it has been shown that eEF2K can be activated in dendrites by metabotropic glutamate receptor (mGluR) 1/5 signaling, as well. Therefore, neuronal activity can induce local proteomic changes at the postsynapse by altering eEF2K activity. Well-established targets of eEF2K in dendrites include brain-derived neurotrophic factor (BDNF), activity-regulated cytoskeletal-associated protein (Arc), the alpha subunit of calcium/CaM-dependent protein kinase II (\u3b1CaMKII), and microtubule-associated protein 1B (MAP1B), all of which have well-known functions in different forms of synaptic plasticity. In this review we will give an overview of the involvement of the eEF2K/eEF2 pathway at dendrites in regulating the translation of dendritic mRNA in the context of altered NMDAR- and neuronal activity, and diverse forms of synaptic plasticity, such as metabotropic glutamate receptor-dependent-long-term depression (mGluR-LTD). For this, we draw on studies carried out both in vitro and in vivo

SAP97-mediated local trafficking is altered in Alzheimer disease patients' hippocampus

Synapse-asssociated protein-97 (SAP97) is responsible for the trafficking of both glutamate receptor subunits, GluR1 and NR2A, and \u3b1-secretase ADAM10 to the synaptic membrane. Here we evaluate the trafficking capability of SAP97 in Alzheimer disease (AD) patients' brain. We analyzed autoptic hippocampus and superior frontal gyrus, respectively as an affected and a less affected area, from 6 AD patients (Braak 4) and 6 healthy controls. In hippocampus, but not in superior frontal gyrus, of AD patients, ADAM10 and GluR1 synaptic membrane levels are altered while NR2A localization is not affected. Both immunoprecipitation and pull-down assays demonstrated that SAP97 failed to correctly couple to ADAM10 and GluR1, but not to NR2A. These findings not only indicate SAP97 as a point of convergence between amyloid cascade and synaptic failure in AD, but also allow a different interpretation of AD which can be now perceived as synaptic trafficking defect patholog

Analysis of mRNA and Protein Levels of CAP2, DLG1 and ADAM10 Genes in Post‐Mortem Brain of Schizophrenia, Parkinson’s and Alzheimer’s Disease Patients

Schizophrenia (SCZ) is a mental illness characterized by aberrant synaptic plasticity and connectivity. A large bulk of evidence suggests genetic and functional links between postsynaptic abnormalities and SCZ. Here, we performed quantitative PCR and Western blotting analysis in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of SCZ patients to investigate the mRNA and protein expression of three key spine shapers: the actin‐binding protein cyclase‐associated protein 2 (CAP2), the sheddase a disintegrin and metalloproteinase 10 (ADAM10), and the synapse-associated protein 97 (SAP97). Our analysis of the SCZ post‐mortem brain indicated increased DLG1 mRNA in DLPFC and decreased CAP2 mRNA in the hippocampus of SCZ patients, compared to non‐psychiatric control subjects, while the ADAM10 transcript was unaffected. Conversely, no differences in CAP2, SAP97, and ADAM10 protein levels were detected between SCZ and control individuals in both brain regions. To assess whether DLG1 and CAP2 transcript alterations were selective for SCZ, we also measured their expression in the superior frontal gyrus of patients affected by neurodegenerative disorders, like Parkinson’s and Alzheimer’s disease. Interestingly, also in Parkinson’s disease patients, we found a selective reduction of CAP2 mRNA levels relative to controls but unaltered protein levels. Taken together, we reported for the first time altered CAP2 expression in the brain of patients with psychiatric and neurological disorders, thus suggesting that aberrant expression of this gene may contribute to synaptic dysfunction in these neuropathologies

Analysis of mRNA and Protein Levels of CAP2, DLG1 and ADAM10 Genes in Post‐Mortem Brain of Schizophrenia, Parkinson’s and Alzheimer’s Disease Patients

Schizophrenia (SCZ) is a mental illness characterized by aberrant synaptic plasticity and connectivity. A large bulk of evidence suggests genetic and functional links between postsynaptic abnormalities and SCZ. Here, we performed quantitative PCR and Western blotting analysis in the dorsolateral prefrontal cortex (DLPFC) and hippocampus of SCZ patients to investigate the mRNA and protein expression of three key spine shapers: the actin‐binding protein cyclase‐associated protein 2 (CAP2), the sheddase a disintegrin and metalloproteinase 10 (ADAM10), and the synapse-associated protein 97 (SAP97). Our analysis of the SCZ post‐mortem brain indicated increased DLG1 mRNA in DLPFC and decreased CAP2 mRNA in the hippocampus of SCZ patients, compared to non‐psychiatric control subjects, while the ADAM10 transcript was unaffected. Conversely, no differences in CAP2, SAP97, and ADAM10 protein levels were detected between SCZ and control individuals in both brain regions. To assess whether DLG1 and CAP2 transcript alterations were selective for SCZ, we also measured their expression in the superior frontal gyrus of patients affected by neurodegenerative disorders, like Parkinson’s and Alzheimer’s disease. Interestingly, also in Parkinson’s disease patients, we found a selective reduction of CAP2 mRNA levels relative to controls but unaltered protein levels. Taken together, we reported for the first time altered CAP2 expression in the brain of patients with psychiatric and neurological disorders, thus suggesting that aberrant expression of this gene may contribute to synaptic dysfunction in these neuropathologies