scholarly journals Regulation of cellular plasticity and resilience by mood stabilizers: the role of AMPA receptor trafficking

2004 ◽  
Vol 6 (2) ◽  
pp. 143-155
Keyword(s):  
Mood Disorders ◽  
Neural Plasticity ◽  
Neuronal Plasticity ◽  
Brain Volume ◽  
Critical Role ◽  
Receptor Trafficking ◽  
Mood Stabilizers ◽  
Brain Areas ◽  
Cellular Resilience

There is increasing evidence from a variety of sources that severe mood disorders are associated with regional reductions in brain volume, as well as reductions in the number, size, and density of glia and neurons in discrete brain areas. Although the precise pathophysiology underlying these morphometric changes remains to be fully elucidated, the data suggest that severe mood disorders are associated with impairments of structural plasticity and cellular resilience. In this context, it is noteworthy that a growing body of data suggests that the glutamaiergic system (which is known to play a major role in neuronal plasticity and cellular resilience) may be involved in the pathophysiology and treatment of mood disorders. Glutamate α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) GluR1 receptor trafficking plays a critical role in regulating various forms of neural plasticity. It is thus noteworthy that recent studies have shown that structurally dissimilar mood stabilizers lithium and valproate regulate GluR1 receptor subunit trafficking and localization at synapses. These studies suggest that regulation of glutamatergically mediated synaptic plasticity may play a role in the treatment of mood disorders, and raises the possibility that agents more directly affecting synaptic GluR1 represent novel therapies for these devastating illnesses.

scholarly journals Bipolar disorder: involvement of signaling cascades and AMPA receptor trafficking at synapses

2004 ◽  
Vol 1 (3) ◽  
pp. 231-243 ◽  
Author(s):  
JING DU ◽  
JORGE QUIROZ ◽  
PEIXIONG YUAN ◽  
CARLOS ZARATE ◽  
HUSSEINI K. MANJI
Keyword(s):  
Synaptic Plasticity ◽  
Mood Disorders ◽  
Ampa Receptor ◽  
Glycogen Synthase ◽  
Receptor Trafficking ◽  
Mood Stabilizers ◽  
Signaling Cascades ◽  
Glutamatergic System ◽  
Ample Evidence ◽  
Cellular Resilience

There is increasing evidence that severe mood disorders are associated with impairment of structural plasticity and cellular resilience. Cumulative data demonstrate that mood stabilizers regulate intracellular signaling cascades, including protein kinase C (PKC), PKA, mitogen-activated protein (MAP) kinase, glycogen synthase kinase 3-β (GSK3-β) and intracellular calcium, which are signaling pathways that regulate synaptic plasticity. In this context, it is noteworthy that a growing body of data indicates that the glutamatergic system, has a major role in neuronal plasticity and cellular resilience, might be involved in the pathophysiology and treatment of mood disorders. AMPA glutamate-receptor trafficking is important in synaptic plasticity and might play crucial roles in maintaining critical neuronal circuits associated with mood. Two clinically effective, structurally dissimilar, antimanic agents, lithium and valproate (VPA), down-regulate synaptic expression of AMPA receptor subunit GluR1 in hippocampus in chronically treated rats. This reduction in synaptic GluR1 by lithium and VPA is due to attenuated phosphorylation of GluR1 at a specific PKA site (residue 845 of GluR1), which is crucial for AMPA receptor insertion. By contrast, imipramine, which can provoke mania, increases synaptic expression of GluR1 in the hippocampus in vivo. Furthermore, there is ample evidence from preclinical and clinical research that the glutamatergic system is involved in the pathophysiology of mood disorders and that many of the somatic treatments used for mood disorders including antidepressants, mood stabilizers, atypical antipsychotic drugs and electroconvulsive therapy have both direct and indirect effects on the glutamatergic system. Given these findings, further research with medications that specifically affect the glutamatergic system is warranted. Recent studies in our lab have shown that riluzole, a FDA approved medicine that regulates the glutamatergic system, shows antidepressant efficacy in unipolar and bipolar depression. These studies indicate that regulation of glutamate-mediated synaptic plasticity might play a role in the treatment of mood disorders, and raise new avenues for novel therapies for this devastating illness.

scholarly journals Neural Plasticity Associated with Hippocampal PKA-CREB and NMDA Signaling Is Involved in the Antidepressant Effect of Repeated Low Dose of Yueju Pill on Chronic Mouse Model of Learned Helplessness

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Zhilu Zou ◽  
Yin Chen ◽  
Qinqin Shen ◽  
Xiaoyan Guo ◽  
Yuxuan Zhang ◽  
...  
Keyword(s):  
Neural Plasticity ◽  
Learned Helplessness ◽  
Low Dose ◽  
Critical Role ◽  
Repeated Administration ◽  
Camp Response Element Binding ◽  
Antidepressant Effect ◽  
Long Term Depression

Yueju pill is a traditional Chinese medicine formulated to treat syndromes of mood disorders. Here, we investigated the therapeutic effect of repeated low dose of Yueju in the animal model mimicking clinical long-term depression condition and the role of neural plasticity associated with PKA- (protein kinase A-) CREB (cAMP response element binding protein) and NMDA (N-methyl-D-aspartate) signaling. We showed that a single low dose of Yueju demonstrated antidepressant effects in tests of tail suspension, forced swim, and novelty-suppressed feeding. A chronic learned helplessness (LH) protocol resulted in a long-term depressive-like condition. Repeated administration of Yueju following chronic LH remarkably alleviated all of depressive-like symptoms measured, whereas conventional antidepressant fluoxetine only showed a minor improvement. In the hippocampus, Yueju and fluoxetine both normalized brain-derived neurotrophic factor (BDNF) and PKA level. Only Yueju, not fluoxetine, rescued the deficits in CREB signaling. The chronic LH upregulated the expression of NMDA receptor subunits NR1, NR2A, and NR2B, which were all attenuated by Yueju. Furthermore, intracerebraventricular administration of NMDA blunted the antidepressant effect of Yueju. These findings supported the antidepressant efficacy of repeated routine low dose of Yueju in a long-term depression model and the critical role of CREB and NMDA signaling.

scholarly journals Chronobiology and mood disorders

2003 ◽  
Vol 5 (4) ◽  
pp. 315-325 ◽  
Keyword(s):  
Circadian Rhythms ◽  
Sleep Deprivation ◽  
Mood Disorders ◽  
Seasonal Affective Disorder ◽  
Bright Light ◽  
Mood Stabilizers ◽  
Phase Advance ◽  
Diagnostic Systems ◽  
Recovery Sleep

The clinical observations of diurnal variation of mood and early morning awakening in depression have been incorporated into established diagnostic systems, as has the seasonal modifier defining winter depression (seasonal affective disorder, SAD). Many circadian rhythms measured in depressive patients are abnormal: earlier in timing, diminished in amplitude, or of greater variability. Whether these disturbances are of etiological significance for the role of circadian rhythms in mood disorders, or a consequence of altered behavior can only be dissected out with stringent protocols (eg, constant routine or forced desynchrony). These protocols quantify contributions of the circadian pacemaker and a homeostatic sleep process impacting on mood, energy, appetite, and sleep. Future studies will elucidate any allelic mutations in "circadian clock" -related or "sleep"-related genes in depression. With respect to treatment, antidepressants and mood stabilizers have no consistent effect on circadian rhythmicity. The most rapid antidepressant modality known so far is nonpharmacological: total or partial sleep deprivation in the second half of the night. The disadvantage of sleep deprivation, that most patients relapse after recovery sleep, can be prevented by coadministration of lithium, pindolol, serotonin (5-HT) reuptake inhibitors, bright light, or a subsequent phase-advance procedure. Phase advance of the sleep-wake cycle alone also has rapid effects on depressed mood, which lasts longer than sleep deprivation. Light is the treatment of choice for SAD and may prove to be useful for nonseasonal depression, alone or as an adjunct to medication. Chronobiological concepts emphasize the important role of zeitgebers to stabilize phase, light being the most important, but dark (and rest) periods, regularity of social schedules and meal times, and use of melatonin or its analogues should also be considered. Advances in chronobiology continue to contribute novel treatments for affective disorders.

Role of glial cell line-derived neurotrophic factor in the pathogenesis and treatment of mood disorders

2017 ◽  
Vol 28 (3) ◽  
pp. 219-233 ◽  
Author(s):  
Anton S. Tsybko ◽  
Tatiana V. Ilchibaeva ◽  
Nina K. Popova
Keyword(s):  
Cell Line ◽  
Mood Disorders ◽  
Glial Cell ◽  
Neurotrophic Factor ◽  
Depressive Disorders ◽  
Bipolar Affective Disorder ◽  
Antidepressant Drugs ◽  
Feedback System ◽  
Mood Stabilizers

AbstractGlial cell line-derived neurotrophic factor (GDNF) is widely recognized as a survival factor for dopaminergic neurons, but GDNF has also been shown to promote development, differentiation, and protection of other central nervous system neurons and was thought to play an important role in various neuropsychiatric disorders. Severe mood disorders, such as primarily major depressive disorder and bipolar affective disorder, attract particular attention. These psychopathologies are characterized by structural alterations accompanied by the dysregulation of neuroprotective and neurotrophic signaling mechanisms required for the maturation, growth, and survival of neurons and glia. The main objective of this review is to summarize the recent findings and evaluate the potential role of GDNF in the pathogenesis and treatment of mood disorders. Specifically, it describes (1) the implication of GDNF in the mechanism of depression and in the effect of antidepressant drugs and mood stabilizers and (2) the interrelation between GDNF and brain neurotransmitters, playing a key role in the pathogenesis of depression. This review provides converging lines of evidence that (1) brain GDNF contributes to the mechanism underlying depressive disorders and the effect of antidepressants and mood stabilizers and (2) there is a cross-talk between GDNF and neurotransmitters representing a feedback system: GDNF-neurotransmitters and neurotransmitters-GDNF.

scholarly journals Dependence of Working Memory on Coordinated Activity Across Brain Areas

2022 ◽  
Vol 15 ◽  
Author(s):  
Ehsan Rezayat ◽  
Kelsey Clark ◽  
Mohammad-Reza A. Dehaqani ◽  
Behrad Noudoost
Keyword(s):  
Working Memory ◽  
Brain Area ◽  
Critical Role ◽  
Brain Disorders ◽  
Brain Areas ◽  
Neural Substrate ◽  
Oscillatory Power ◽  
Experimental Findings ◽  
Neural Signatures

Neural signatures of working memory (WM) have been reported in numerous brain areas, suggesting a distributed neural substrate for memory maintenance. In the current manuscript we provide an updated review of the literature focusing on intracranial neurophysiological recordings during WM in primates. Such signatures of WM include changes in firing rate or local oscillatory power within an area, along with measures of coordinated activity between areas based on synchronization between oscillations. In comparing the ability of various neural signatures in any brain area to predict behavioral performance, we observe that synchrony between areas is more frequently and robustly correlated with WM performance than any of the within-area neural signatures. We further review the evidence for alteration of inter-areal synchrony in brain disorders, consistent with an important role for such synchrony during behavior. Additionally, results of causal studies indicate that manipulating synchrony across areas is especially effective at influencing WM task performance. Each of these lines of research supports the critical role of inter-areal synchrony in WM. Finally, we propose a framework for interactions between prefrontal and sensory areas during WM, incorporating a range of experimental findings and offering an explanation for the observed link between intra-areal measures and WM performance.

The Dysregulation of microRNAs and the Role of Stress in the Pathogenesis of Mental Disorders

2019 ◽  
Vol 18 (21) ◽  
pp. 1893-1907 ◽  
Author(s):  
Elena Ivanova ◽  
Radosveta Bozhilova ◽  
Radka Kaneva ◽  
Vihra Milanova
Keyword(s):  
Gene Expression ◽  
Psychiatric Disorders ◽  
Neural Plasticity ◽  
Target Genes ◽  
Morphological Changes ◽  
Critical Role ◽  
Autism Spectrum ◽  
Current State ◽  
Neuronal Gene

MicroRNAs are endogenous small non-coding RNAs that regulate gene expression by means of partial complementarity to microRNA binding sites at their target genes. These molecules have emerged as key regulators of almost every biological process including accurate control of neuronal gene expression. The authors discuss the current state of microRNA research, including studies of psychiatric disorders (schizophrenia, autism spectrum disorder and affective disorders). Stress has also been shown to have a critical role in the development of psychiatric disorders, at least partially, through mechanisms related to neural plasticity. Synaptic connections in the brain undergo experience-dependent functional or morphological changes through complex pathways that are not yet fully understood, but for which microRNAs might have a critical role. The focus is on the role that microRNAs play in the development of psychiatric disorders and their potential to serve as biomarkers of disease as well as targets for pharmacological treatment.

scholarly journals The role of astrocyte‐mediated plasticity in neural circuit development and function

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Nelson A. Perez-Catalan ◽  
Chris Q. Doe ◽  
Sarah D. Ackerman
Keyword(s):  
Nervous System ◽  
Neural Plasticity ◽  
Neural Circuit ◽  
System Development ◽  
Critical Role ◽  
Nervous System Development ◽  
Functional Changes ◽  
Sensory Evoked ◽  
And Function

AbstractNeuronal networks are capable of undergoing rapid structural and functional changes called plasticity, which are essential for shaping circuit function during nervous system development. These changes range from short-term modifications on the order of milliseconds, to long-term rearrangement of neural architecture that could last for the lifetime of the organism. Neural plasticity is most prominent during development, yet also plays a critical role during memory formation, behavior, and disease. Therefore, it is essential to define and characterize the mechanisms underlying the onset, duration, and form of plasticity. Astrocytes, the most numerous glial cell type in the human nervous system, are integral elements of synapses and are components of a glial network that can coordinate neural activity at a circuit-wide level. Moreover, their arrival to the CNS during late embryogenesis correlates to the onset of sensory-evoked activity, making them an interesting target for circuit plasticity studies. Technological advancements in the last decade have uncovered astrocytes as prominent regulators of circuit assembly and function. Here, we provide a brief historical perspective on our understanding of astrocytes in the nervous system, and review the latest advances on the role of astroglia in regulating circuit plasticity and function during nervous system development and homeostasis.

scholarly journals Enhancing synaptic plasticity and cellular resilience to develop novel, improved treatments for mood disorders

2002 ◽  
Vol 4 (1) ◽  
pp. 73-92
Keyword(s):  
Synaptic Plasticity ◽  
Cell Survival ◽  
Signaling Pathways ◽  
Mood Disorders ◽  
Map Kinases ◽  
Adenosine Monophosphate ◽  
Mood Stabilizers ◽  
Cellular Mechanisms ◽  
Cellular Resilience

There is mounting evidence that recurrent mood disorders - once considered "good prognosis diseases"- are, in fact, often very severe and life-threatening illnesses. Furthermore, although mood disorders have traditionally been conceptualized as neurochemical disorders, there is now evidence from a variety of sources demonstrating regional reductions in central nervous system (CNS) volume, as well as reductions in the numbers and/or sizes ofglia and neurons in discrete brain areas. Although the precise cellular mechanisms underlying these morphometric changes remain to be fully elucidated, the data suggest that mood disorders are associated with impairments of synaptic plasticity and cellular resilience. In this context, it is noteworthy that there is increasing preclinical evidence that antidepressants regulate the function of the glutamatergic system. Moreover, although clearly preliminary, the available clinical data suggest that attenuation of N-methyl-D-aspartate (NMDA) function has antidepressant effects. Recent preclinical and clinical studies have shown that signaling pathways involved in regulating cell survival and cell death are long-term targets for the actions of antidepressant agents. Antidepressants and mood stabilizers indirectly regulate a number of factors involved in cell survival pathways, including cyclic adenosine monophosphate (cAMP) response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), the antiapoptotic protein bcl-2, and mitogen-activated protein (MAP) kinases, and may thus bring about some of their delayed long-term beneficial effects via underappreciated neurotrophic effects. There is much promise for the future development of treatments that more directly target molecules in critical CNS signaling pathways regulating synaptic plasticity and cellular resilience. These will represent improved long-term treatments for mood disorders.

scholarly journals Common Brain Substrates Underlying Auditory Speech Priming and Perceived Spatial Separation

2021 ◽  
Vol 15 ◽  
Author(s):  
Junxian Wang ◽  
Jing Chen ◽  
Xiaodong Yang ◽  
Lei Liu ◽  
Chao Wu ◽  
...  
Keyword(s):  
Inferior Frontal Gyrus ◽  
Critical Role ◽  
Spatial Separation ◽  
Anterior Cingulate ◽  
Cocktail Party ◽  
Brain Areas ◽  
Motor Representation ◽  
Auditory Speech ◽  
Perceived Spatial Separation

Under a “cocktail party” environment, listeners can utilize prior knowledge of the content and voice of the target speech [i.e., auditory speech priming (ASP)] and perceived spatial separation to improve recognition of the target speech among masking speech. Previous studies suggest that these two unmasking cues are not processed independently. However, it is unclear whether the unmasking effects of these two cues are supported by common neural bases. In the current study, we aimed to first confirm that ASP and perceived spatial separation contribute to the improvement of speech recognition interactively in a multitalker condition and further investigate whether there exist intersectant brain substrates underlying both unmasking effects, by introducing these two unmasking cues in a unified paradigm and using functional magnetic resonance imaging. The results showed that neural activations by the unmasking effects of ASP and perceived separation partly overlapped in brain areas: the left pars triangularis (TriIFG) and orbitalis of the inferior frontal gyrus, left inferior parietal lobule, left supramarginal gyrus, and bilateral putamen, all of which are involved in the sensorimotor integration and the speech production. The activations of the left TriIFG were correlated with behavioral improvements caused by ASP and perceived separation. Meanwhile, ASP and perceived separation also enhanced the functional connectivity between the left IFG and brain areas related to the suppression of distractive speech signals: the anterior cingulate cortex and the left middle frontal gyrus, respectively. Therefore, these findings suggest that the motor representation of speech is important for both the unmasking effects of ASP and perceived separation and highlight the critical role of the left IFG in these unmasking effects in “cocktail party” environments.

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