Molecular and Cellular Pathogenesis of Depression and Mechanisms for Treatment Response

2013 ◽  
pp. 425-437
Author(s):  
Ronald S. Duman
Keyword(s):  
Amino Acid ◽  
Neurotrophic Factors ◽  
Limbic Structures ◽  
Brain Circuits ◽  
Antidepressant Agent ◽  
Treatment Of Depression ◽  
Cellular Pathogenesis ◽  
Gaba Transmission ◽  
Stress Models ◽  
New Generation

Early theories of depression were centered on the monoamines, but more recent work has focused on the amino acid neurotransmitters, glutamate and GABA. Imbalances of glutamate and GABA transmission in key cortical and limbic structures are thought to contribute to disruption of brain circuits that control emotion and mood. These imbalances, together with stress activated pathways that regulate neurotrophic factors and inflammatory cytokines could contribute to atrophy and loss of neurons observed in depressed patients and rodent stress models. The significance of synaptic connections in depression is highlighted by new studies demonstrating that a rapid acting, highly efficacious antidepressant agent increases synaptogenesis, paving the way for a new generation of medications for the treatment of depression.

Neurotrophic Mechanisms of Depression

2017 ◽  
Author(s):  
Ronald S. Duman
Keyword(s):  
Growth Factor ◽  
Neurotrophic Factors ◽  
Synapse Formation ◽  
Chronic Administration ◽  
Adaptive Plasticity ◽  
Treatment Of Depression ◽  
Cortical Regions ◽  
Stress Models ◽  
New Generation ◽  
Endothelial Growth Factor

Early theories of depression and treatment response were centered on the monoamine neurotransmitters, but more recent work has focused on functional and structural synaptic plasticity and the role of neurotrophic factors, particularly brain derived neurotrophic factor (BDNF). Neurotrophic factors regulate all aspects of neuronal function, including adaptive plasticity, synapse formation, and neuronal survival. Chronic stress and depression cause reductions in levels of BDNF and other key factors, including vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF2), in cortical regions that contribute to atrophy and loss of neurons observed in depressed patients and rodent stress models. In contrast, these neurotrophic factors are upregulated by chronic administration of typical antidepressants and are required for antidepressant responses. Moreover, fast acting, highly efficacious antidepressant agents such as ketamine rapidly increase BDNF release and synapse formation, paving the way for a new generation of medications for the treatment of depression.

scholarly journals Exchange of a single amino acid interconverts the specific activity and gel mobility of human and rat ciliary neurotrophic factors.

1993 ◽  
Vol 268 (25) ◽  
pp. 19000-19003
Author(s):  
N. Panayotatos ◽  
E. Radziejewska ◽  
A. Acheson ◽  
D. Pearsall ◽  
A. Thadani ◽  
...  
Keyword(s):  
Amino Acid ◽  
Neurotrophic Factors ◽  
Specific Activity ◽  
Single Amino Acid

scholarly journals Tetraconatan phylogeny with special focus on Malacostraca and Branchiopoda: highlighting the strength of taxon-specific matrices in phylogenomics

2018 ◽  
Vol 285 (1885) ◽  
pp. 20181524 ◽  
Author(s):  
Martin Schwentner ◽  
Stefan Richter ◽  
D. Christopher Rogers ◽  
Gonzalo Giribet
Keyword(s):  
Amino Acid ◽  
Analytical Methods ◽  
Special Focus ◽  
Evolutionary Models ◽  
Phylogenomic Analyses ◽  
New Generation ◽  
Analytical Approaches ◽  
Internal Relationships ◽  
Complete Matrix ◽  
Phylogenomic Study

Understanding the evolution of Tetraconata or Pancrustacea—the clade that includes crustaceans and insects—requires a well-resolved hypothesis regarding the relationships within and among its constituent taxa. Here, we assembled a taxon-rich phylogenomic dataset focusing on crustacean lineages based solely on genomes and new-generation Illumina-generated transcriptomes, including 89 representatives of Tetraconata. This constitutes, to our knowledge, the first phylogenomic study specifically addressing internal relationships of Malacostraca (with 26 species included) and Branchiopoda (36 species). Seven matrices comprising 81–684 orthogroups and 17 690–242 530 amino acid positions were assembled and analysed under five different analytical approaches. To maximize gene occupancy and to improve resolution, taxon-specific matrices were designed for Malacostraca and Branchiopoda. Key tetraconatan taxa (i.e. Oligostraca, Multicrustacea, Branchiopoda, Malacostraca, Thecostraca, Copepoda and Hexapoda) were monophyletic and well supported. Within Branchiopoda, Phyllopoda, Diplostraca, Cladoceromorpha and Cladocera were monophyletic. Within Malacostraca, the clades Eumalacostraca, Decapoda and Reptantia were well supported. Recovery of Caridoida or Peracarida was highly dependent on the analysis for the complete matrix, but it was consistently monophyletic in the malacostracan-specific matrices. From such examples, we demonstrate that taxon-specific matrices and particular evolutionary models and analytical methods, namely CAT-GTR and Dayhoff recoding, outperform other approaches in resolving certain recalcitrant nodes in phylogenomic analyses.

Pincer ligands based on α-amino acids: V. New generation chiral receptors for the recognition of amino acid enantiomers in aqueous environment

2011 ◽  
Vol 47 (2) ◽  
pp. 193-201
Author(s):  
N. E. Borisova ◽  
F. E. Zhurkin ◽  
T. G. Gulevich ◽  
K. K. Babievskii ◽  
M. D. Reshetova ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Pincer Ligands ◽  
Aqueous Environment ◽  
Amino Acid Enantiomers ◽  
New Generation ◽  
Chiral Receptors

Targeting histidine for developing a new generation of covalent enzyme inhibitors

2021 ◽  
Vol 17 ◽  
Author(s):  
Donald Poirier
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Drug Development ◽  
Chemical Bond ◽  
Amino Acid Residue ◽  
Enzyme Inhibitors ◽  
Irreversible Inhibitors ◽  
Covalent Inhibitors ◽  
Targeted Inhibitors ◽  
New Generation

: Despite the significant number of irreversible inhibitors developed over the years, strong prejudices remain for this type of therapeutic molecule, particularly in the area of drug development. New generations of covalent targeted inhibitors are, however, in development, and interest is increasingly growing. In fact, the new generation of covalent inhibitors has a weakly reactive species (warhead) that is able, in a particular context, to selectively form a chemical bond with a given amino acid residue, which can be irreversible or reversible. In addition to new selective warheads, new amino acids are also targeted. In the following text, we will focus on covalent targeted inhibitors that selectively alkylate histidine.

scholarly journals Metal self-assembly mimosine peptides with enhanced antimicrobial activity: towards a new generation of multitasking chelating agents

2020 ◽  
Vol 49 (9) ◽  
pp. 2862-2879 ◽  
Author(s):  
Joanna Izabela Lachowicz ◽  
Gabriele Dalla Torre ◽  
Rosita Cappai ◽  
Enrico Randaccio ◽  
Valeria M. Nurchi ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Amino Acid ◽  
Self Assembly ◽  
Building Block ◽  
Chelating Agents ◽  
Metal Coordination ◽  
Protein Amino Acid ◽  
Coordination Ability ◽  
New Generation

Mimosine is a non-protein amino acid that can be used as a building block in peptides with metal coordination ability.

Inhibition of group I metabotropic glutamate receptor responses in vivo in rats by a new generation of carboxyphenylglycine-like amino acid antagonists

2002 ◽  
Vol 330 (2) ◽  
pp. 127-130 ◽  
Author(s):  
Ann E Kingston ◽  
Kelly Griffey ◽  
Michael P Johnson ◽  
Mary-Jo Chamberlain ◽  
Gerald Kelly ◽  
...  
Keyword(s):  
Amino Acid ◽  
Glutamate Receptor ◽  
Metabotropic Glutamate Receptor ◽  
Metabotropic Glutamate ◽  
Group I ◽  
Amino Acid Antagonists ◽  
New Generation

Drug Treatment of Depression

1990 ◽  
Vol 3 (4) ◽  
pp. 252-261
Author(s):  
Candace S. Brown ◽  
Stephen G. Bryant
Keyword(s):  
Side Effects ◽  
Major Depression ◽  
Drug Treatment ◽  
Depressed Patient ◽  
First Generation ◽  
Second Generation ◽  
Treatment Of Depression ◽  
New Generation

The major advantage of the new generation of antidepressants lies in their enhanced ability to avoid unwanted side effects, such as anticholinergic or cardiovascular toxicities, and in many cases, to reduce fatalities after overdose. Second-generation antidepressants are as effective as the first generation agents, but are more selective, enabling precise targeting of symptoms. Caution in recommending the newer antidepressants must be applied, however, because these agents possess differing side effects, and unforeseen toxicities may not appear until after several years of use. Conventional tricyclics should not be overlooked in managing the depressed patient. This article discusses the symptoms of major depression, followed by the latest information on second-generation antidepressants. It concludes by providing the pharmacist with guidelines for when to select a newer over an older agent.

scholarly journals Sequence learning in a single trial: a spiking neurons model based on hippocampal circuitry

2020 ◽  
Author(s):  
S. Coppolino ◽  
M. Migliore
Keyword(s):  
Cognitive Functions ◽  
Network Architecture ◽  
Single Trial ◽  
Additional Advantage ◽  
Brain Circuits ◽  
Correct Sequence ◽  
Long Time ◽  
New Generation ◽  
Learning Architectures ◽  
The Way

ABSTRACTIn contrast with our everyday experience using brain circuits, it can take a prohibitively long time to train a computational system to produce the correct sequence of outputs in the presence of a series of inputs. This suggests that something important is missing in the way in which models are trying to reproduce basic cognitive functions. In this work, we introduce a new neuronal network architecture that is able to learn, in a single trial, an arbitrary long sequence of any known objects. The key point of the model is the explicit use of mechanisms and circuitry observed in the hippocampus, which allow the model to reach a level of efficiency and accuracy that, to the best of our knowledge, is not possible with abstract network implementations. By directly following the natural system’s layout and circuitry, this type of implementation has the additional advantage that the results can be more easily compared to experimental data, allowing a deeper and more direct understanding of the mechanisms underlying cognitive functions and dysfunctions, and opening the way to a new generation of learning architectures.

The Use of Ketamine as Therapy for Depression

2021 ◽  
Vol 1 (2) ◽  
pp. 28-31
Author(s):  
Lovina Lovina
Keyword(s):  
Chronic Pain ◽  
Clinical Practice ◽  
Side Effects ◽  
Developed Countries ◽  
Rapid Onset ◽  
Systemic Arterial Pressure ◽  
Chronic Pain Management ◽  
Extracellular Glutamate ◽  
Treatment Of Depression ◽  
New Generation

Depressive disorder is still a significant problem in several developed countries and is morbidity caused by mental disorders. With the development of science, now discovered the unique pharmacodynamic properties of ketamine, which is used as an antidepressant. As we know in clinical practice, ketamine is used for anaesthesia, analgesia, sedation, and chronic pain management. Rapid-onset antidepressants resulted from increased levels of BDNF in the hippocampus. Extracellular glutamate agents are not new for the treatment of depression. According to the neurobiology view, depression is a monoaminergic phenomenon, so this is the impetus for discovering a new generation of antidepressants. Ketamine can be given intravenously in subanesthetic doses. Still, monitoring must be carrying in therapy administration because of the possible side effects such as hypersalivation, tachycardia, increased systemic arterial pressure, and intracranial pressure.

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