scholarly journals Cellular resilience and baboon aging

Aging ◽  
2021 ◽  
Author(s):  
Daniel A. Adekunbi ◽  
Peter W. Nathanielsz ◽  
Adam B. Salmon
Keyword(s):  
Cellular Resilience

scholarly journals Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts

2020 ◽  
Author(s):  
Kerstin Kuffner ◽  
Julian Triebelhorn ◽  
Katrin Meindl ◽  
Christoph Benner ◽  
André Manook ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Oxygen Consumption ◽  
Depressive Disorder ◽  
Mitochondrial Function ◽  
Skin Fibroblasts ◽  
Major Depressive ◽  
Molecular Pathophysiology ◽  
Molecular Pathomechanisms ◽  
Adult Human Skin ◽  
Cellular Resilience

Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial disfunction in adult human skin fibroblasts which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and ATP-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance which is associated with the molecular pathophysiology of MDD. The observed alterations in OXPHOS and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways.

scholarly journals Nrf2 dysfunction and impaired cellular resilience to oxidative stressors in the aged vasculature: from increased cellular senescence to the pathogenesis of age-related vascular diseases

GeroScience ◽  
2019 ◽  
Vol 41 (6) ◽  
pp. 727-738 ◽  
Author(s):  
Zoltan Ungvari ◽  
Stefano Tarantini ◽  
Ádám Nyúl-Tóth ◽  
Tamas Kiss ◽  
Andriy Yabluchanskiy ◽  
...  
Keyword(s):  
Cellular Senescence ◽  
Vascular Diseases ◽  
Age Related ◽  
Cellular Resilience

scholarly journals Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for Difficult-to-Treat depression

2003 ◽  
Vol 53 (8) ◽  
pp. 707-742 ◽  
Author(s):  
Husseini K Manji ◽  
Jorge A Quiroz ◽  
Jonathan Sporn ◽  
Jennifer L Payne ◽  
Kirk Denicoff ◽  
...  
Keyword(s):  
Neuronal Plasticity ◽  
Cellular Resilience

scholarly journals A LUHMES 3D dopaminergic neuronal model for neurotoxicity testing allowing long-term exposure and cellular resilience analysis

2015 ◽  
Vol 90 (11) ◽  
pp. 2725-2743 ◽  
Author(s):  
L. Smirnova ◽  
G. Harris ◽  
J. Delp ◽  
M. Valadares ◽  
D. Pamies ◽  
...  
Keyword(s):  
Neuronal Model ◽  
Cellular Resilience

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 Major Depressive Disorder is Associated with Impaired Mitochondrial Function in Skin Fibroblasts

Cells ◽  
2020 ◽  
Vol 9 (4) ◽  
pp. 884
Author(s):  
Kerstin Kuffner ◽  
Julian Triebelhorn ◽  
Katrin Meindl ◽  
Christoph Benner ◽  
André Manook ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Oxygen Consumption ◽  
Depressive Disorder ◽  
Mitochondrial Function ◽  
Skin Fibroblasts ◽  
Major Depressive ◽  
Molecular Pathophysiology ◽  
Molecular Pathomechanisms ◽  
Adult Human Skin ◽  
Cellular Resilience

Mitochondrial malfunction is supposed to be involved in the etiology and pathology of major depressive disorder (MDD). Here, we aimed to identify and characterize the molecular pathomechanisms related to mitochondrial dysfunction in adult human skin fibroblasts, which were derived from MDD patients or non-depressive control subjects. We found that MDD fibroblasts showed significantly impaired mitochondrial functioning: basal and maximal respiration, spare respiratory capacity, non-mitochondrial respiration and adenosine triphosphate (ATP)-related oxygen consumption was lower. Moreover, MDD fibroblasts harbor lower ATP levels and showed hyperpolarized mitochondrial membrane potential. To investigate cellular resilience, we challenged both groups of fibroblasts with hormonal (dexamethasone) or metabolic (galactose) stress for one week, and found that both stressors increased oxygen consumption but lowered ATP content in MDD as well as in non-depressive control fibroblasts. Interestingly, the bioenergetic differences between fibroblasts from MDD or non-depressed subjects, which were observed under non-treated conditions, could not be detected after stress. Our findings support the hypothesis that altered mitochondrial function causes a bioenergetic imbalance, which is associated with the molecular pathophysiology of MDD. The observed alterations in the oxidative phosphorylation system (OXPHOS) and other mitochondria-related properties represent a basis for further investigations of pathophysiological mechanisms and might open new ways to gain insight into antidepressant signaling pathways.

Cellular resilience: 5-HT neurons in Tph2−/− mice retain normal firing behavior despite the lack of brain 5-HT

2015 ◽  
Vol 25 (11) ◽  
pp. 2022-2035 ◽  
Author(s):  
Alberto Montalbano ◽  
Jonas Waider ◽  
Mario Barbieri ◽  
Ozan Baytas ◽  
Klaus-Peter Lesch ◽  
...  
Keyword(s):  
Firing Behavior ◽  
Cellular Resilience

scholarly journals Neuroplasticity and cellular resilience in mood disorders

2000 ◽  
Vol 5 (6) ◽  
pp. 578-593 ◽  
Author(s):  
H K Manji ◽  
G J Moore ◽  
G Rajkowska ◽  
G Chen
Keyword(s):  
Mood Disorders ◽  
Cellular Resilience

scholarly journals Biological Pathways Associated with Neuroprogression in Bipolar Disorder

2021 ◽  
Vol 11 (2) ◽  
pp. 228
Author(s):  
Bianca Wollenhaupt-Aguiar ◽  
Flavio Kapczinski ◽  
Bianca Pfaffenseller
Keyword(s):  
Bipolar Disorder ◽  
Clinical Outcomes ◽  
Biological Pathways ◽  
Molecular Pathways ◽  
Clinical Progression ◽  
Biological Basis ◽  
And Biological Markers ◽  
Illness Progression ◽  
Novel Therapeutic ◽  
Cellular Resilience

There is evidence suggesting clinical progression in a subset of patients with bipolar disorder (BD). This progression is associated with worse clinical outcomes and biological changes. Molecular pathways and biological markers of clinical progression have been identified and may explain the progressive changes associated with this disorder. The biological basis for clinical progression in BD is called neuroprogression. We propose that the following intertwined pathways provide the biological basis of neuroprogression: inflammation, oxidative stress, impaired calcium signaling, endoplasmic reticulum and mitochondrial dysfunction, and impaired neuroplasticity and cellular resilience. The nonlinear interaction of these pathways may worsen clinical outcomes, cognition, and functioning. Understanding neuroprogression in BD is crucial for identifying novel therapeutic targets, preventing illness progression, and ultimately promoting better outcomes.

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.

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