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Cellular consequences of stress and depression.

Fuchs E, Flügge G - Dialogues Clin Neurosci (2004)

Bottom Line: Stress is known to activate distinct neuronal circuits in the brain and induce multiple changes on the cellular level, including alterations in neuronal structures.Antidepressants are presently believed to exert their primary biochemical effects by readjusting aberrant intrasynaptic concentrations of neurotransmitters, such as serotonin or noradrenaline, suggesting that imbalances viihin the monoaminergic systems contribute to the disorder (monoaminergic hypothesis of depression).Here, we reviev the results that comprise our understanding of stressful experience on cellular processes, with particular focus on the monoaminergic systems and structural changes within brain target areas of monoaminergic neurons.

View Article: PubMed Central - PubMed

Affiliation: Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany.

ABSTRACT
Stress is known to activate distinct neuronal circuits in the brain and induce multiple changes on the cellular level, including alterations in neuronal structures. On the basis of clinical observations that stress often precipitates a depressive disease, chronic psychosocial stress serves as an experimental model to evaluate the cellular and molecular alterations associated with the consequences of major depression. Antidepressants are presently believed to exert their primary biochemical effects by readjusting aberrant intrasynaptic concentrations of neurotransmitters, such as serotonin or noradrenaline, suggesting that imbalances viihin the monoaminergic systems contribute to the disorder (monoaminergic hypothesis of depression). Here, we reviev the results that comprise our understanding of stressful experience on cellular processes, with particular focus on the monoaminergic systems and structural changes within brain target areas of monoaminergic neurons.

No MeSH data available.


Related in: MedlinePlus

Neurotransmission via a G protein-coupled receptor (GPCR): binding of the neurotransmitter to the receptor initiates a cascade of intracellular events that drive the activity of the neuron or cell. The G-protein complex, consisting of subunits α, β, and γ, serves as the machinery that transduces the extracellular signal to various effectors at the intracellular side of the plasma membrane, to the enzymes adenylyl cyclase or phospholipase. These enzymes catalyze the synthesis of second messengers, such as cyclic adenosine monophosphate (cAMP) and diacylglycerol, which regulate gene transcription in the nucleus. Transcripts (mRNA) are later translated into protein. Calcium ions released from intracellular stores and other second messengers activate protein kinases and phosphatases. This leads to phosphorylation and/or dephosphorylation of many intracellular proteins as well as ion channels that are located in the plasma membrane of the cell. Phosphorylation/dephosphorylation induces opening and closing of these channels and this modulates the electrical activity of the neuron. These dynamic cellular processes are accelerated during stress when neurotransmitter concentrations are elevated.
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DialoguesClinNeurosci-6-171-g002: Neurotransmission via a G protein-coupled receptor (GPCR): binding of the neurotransmitter to the receptor initiates a cascade of intracellular events that drive the activity of the neuron or cell. The G-protein complex, consisting of subunits α, β, and γ, serves as the machinery that transduces the extracellular signal to various effectors at the intracellular side of the plasma membrane, to the enzymes adenylyl cyclase or phospholipase. These enzymes catalyze the synthesis of second messengers, such as cyclic adenosine monophosphate (cAMP) and diacylglycerol, which regulate gene transcription in the nucleus. Transcripts (mRNA) are later translated into protein. Calcium ions released from intracellular stores and other second messengers activate protein kinases and phosphatases. This leads to phosphorylation and/or dephosphorylation of many intracellular proteins as well as ion channels that are located in the plasma membrane of the cell. Phosphorylation/dephosphorylation induces opening and closing of these channels and this modulates the electrical activity of the neuron. These dynamic cellular processes are accelerated during stress when neurotransmitter concentrations are elevated.

Mentions: The noradrenergic and adrenergic neurons are located in the brain stem, where they form groups of cells that project axons to many parts of the brain. The beststudied group of noradrenergic neurons, located in the pontine locus ceruleus (LC), innervate several brain regions including the neocortex and the limbic system. The limbic system is a collection of regions that appear to regulate emotional processes (Figure 1). The noradrenergic LC neurons play an important role in the regulation of mood and emotions as well as of attention span. When stimulated through stressful challenge, for example, noradrenaline is released from the nerve terminals in the target brain region and is bound to adrenergic receptors belonging to the group of G protein-coupled receptors (GPCRs). These membrane-bound proteins convey signals from the extracellular to the intracellular compartment of a cell (Figure 2). GPCR signaling requires several steps for transmission of the signal, lasting from milliseconds to many minutes. The binding of a natural agonist such as noradrenaline or adrenaline to the receptor initiates a cascade of intracellular events that drive the activity of the cell and involve effectors such as enzymes (eg, adenylyl cyclase, phospholipasc, kinases, and phosphatases), second messengers (eg, cyclic adenosine monophosphate f[cAMP], cyclic guanosine monophosphate [cGMP], calcium ions, and arachidonic acid), as well as ion channels, which modulate the electrical activity of the neuron. A long-term effect occurring minutes after binding GPCR is the regulation of gene transcription and subsequent protein synthesis (Figure 2).5 There are different types of adrenergic receptors in the brain whose activation either stimulates or inhibits the respective target neurons. Noradrenaline and adrenaline bind to the same types of adrenergic receptors, although with slightly different affinities.6


Cellular consequences of stress and depression.

Fuchs E, Flügge G - Dialogues Clin Neurosci (2004)

Neurotransmission via a G protein-coupled receptor (GPCR): binding of the neurotransmitter to the receptor initiates a cascade of intracellular events that drive the activity of the neuron or cell. The G-protein complex, consisting of subunits α, β, and γ, serves as the machinery that transduces the extracellular signal to various effectors at the intracellular side of the plasma membrane, to the enzymes adenylyl cyclase or phospholipase. These enzymes catalyze the synthesis of second messengers, such as cyclic adenosine monophosphate (cAMP) and diacylglycerol, which regulate gene transcription in the nucleus. Transcripts (mRNA) are later translated into protein. Calcium ions released from intracellular stores and other second messengers activate protein kinases and phosphatases. This leads to phosphorylation and/or dephosphorylation of many intracellular proteins as well as ion channels that are located in the plasma membrane of the cell. Phosphorylation/dephosphorylation induces opening and closing of these channels and this modulates the electrical activity of the neuron. These dynamic cellular processes are accelerated during stress when neurotransmitter concentrations are elevated.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3181796&req=5

DialoguesClinNeurosci-6-171-g002: Neurotransmission via a G protein-coupled receptor (GPCR): binding of the neurotransmitter to the receptor initiates a cascade of intracellular events that drive the activity of the neuron or cell. The G-protein complex, consisting of subunits α, β, and γ, serves as the machinery that transduces the extracellular signal to various effectors at the intracellular side of the plasma membrane, to the enzymes adenylyl cyclase or phospholipase. These enzymes catalyze the synthesis of second messengers, such as cyclic adenosine monophosphate (cAMP) and diacylglycerol, which regulate gene transcription in the nucleus. Transcripts (mRNA) are later translated into protein. Calcium ions released from intracellular stores and other second messengers activate protein kinases and phosphatases. This leads to phosphorylation and/or dephosphorylation of many intracellular proteins as well as ion channels that are located in the plasma membrane of the cell. Phosphorylation/dephosphorylation induces opening and closing of these channels and this modulates the electrical activity of the neuron. These dynamic cellular processes are accelerated during stress when neurotransmitter concentrations are elevated.
Mentions: The noradrenergic and adrenergic neurons are located in the brain stem, where they form groups of cells that project axons to many parts of the brain. The beststudied group of noradrenergic neurons, located in the pontine locus ceruleus (LC), innervate several brain regions including the neocortex and the limbic system. The limbic system is a collection of regions that appear to regulate emotional processes (Figure 1). The noradrenergic LC neurons play an important role in the regulation of mood and emotions as well as of attention span. When stimulated through stressful challenge, for example, noradrenaline is released from the nerve terminals in the target brain region and is bound to adrenergic receptors belonging to the group of G protein-coupled receptors (GPCRs). These membrane-bound proteins convey signals from the extracellular to the intracellular compartment of a cell (Figure 2). GPCR signaling requires several steps for transmission of the signal, lasting from milliseconds to many minutes. The binding of a natural agonist such as noradrenaline or adrenaline to the receptor initiates a cascade of intracellular events that drive the activity of the cell and involve effectors such as enzymes (eg, adenylyl cyclase, phospholipasc, kinases, and phosphatases), second messengers (eg, cyclic adenosine monophosphate f[cAMP], cyclic guanosine monophosphate [cGMP], calcium ions, and arachidonic acid), as well as ion channels, which modulate the electrical activity of the neuron. A long-term effect occurring minutes after binding GPCR is the regulation of gene transcription and subsequent protein synthesis (Figure 2).5 There are different types of adrenergic receptors in the brain whose activation either stimulates or inhibits the respective target neurons. Noradrenaline and adrenaline bind to the same types of adrenergic receptors, although with slightly different affinities.6

Bottom Line: Stress is known to activate distinct neuronal circuits in the brain and induce multiple changes on the cellular level, including alterations in neuronal structures.Antidepressants are presently believed to exert their primary biochemical effects by readjusting aberrant intrasynaptic concentrations of neurotransmitters, such as serotonin or noradrenaline, suggesting that imbalances viihin the monoaminergic systems contribute to the disorder (monoaminergic hypothesis of depression).Here, we reviev the results that comprise our understanding of stressful experience on cellular processes, with particular focus on the monoaminergic systems and structural changes within brain target areas of monoaminergic neurons.

View Article: PubMed Central - PubMed

Affiliation: Clinical Neurobiology Laboratory, German Primate Center, Göttingen, Germany.

ABSTRACT
Stress is known to activate distinct neuronal circuits in the brain and induce multiple changes on the cellular level, including alterations in neuronal structures. On the basis of clinical observations that stress often precipitates a depressive disease, chronic psychosocial stress serves as an experimental model to evaluate the cellular and molecular alterations associated with the consequences of major depression. Antidepressants are presently believed to exert their primary biochemical effects by readjusting aberrant intrasynaptic concentrations of neurotransmitters, such as serotonin or noradrenaline, suggesting that imbalances viihin the monoaminergic systems contribute to the disorder (monoaminergic hypothesis of depression). Here, we reviev the results that comprise our understanding of stressful experience on cellular processes, with particular focus on the monoaminergic systems and structural changes within brain target areas of monoaminergic neurons.

No MeSH data available.


Related in: MedlinePlus