Antidepressant-like actions of minocycline combined with several glutamate antagonists

Molina-Hernández, Miguel; Téllez-Alcántara, N. Patricia; Pérez-García, Julián; Olivera-López, Jorge I.; Jaramillo-Jaimes, M. Teresa

doi:10.1016/j.pnpbp.2007.09.004

Cited by 111 publications

(85 citation statements)

References 59 publications

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“…Therefore, our study provides insight into why immune-and glutamate-modulating therapies may be helpful for acutely ill suicidal patients suffering from depression. Potential candidate drugs include the tetracycline antibiotic minocycline, which inhibits microglial activation by blocking NF-kappa B nuclear translocation [39][40][41][42] or antiinflammatory inhibitors of cyclooxygenase-2 [43,44]. Furthermore, severely depressed suicidal patients may Figure 3 Illustration of QUIN-immunopositive cell densities.…”

Section: Discussionmentioning

confidence: 99%

Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?

Steiner

Walter

Gos

et al. 2012

Neurology, Psychiatry and Brain Research

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Background: Immune dysfunction, including monocytosis and increased blood levels of interleukin-1, interleukin-6 and tumour necrosis factor α has been observed during acute episodes of major depression. These peripheral immune processes may be accompanied by microglial activation in subregions of the anterior cingulate cortex where depression-associated alterations of glutamatergic neurotransmission have been described. Methods: Microglial immunoreactivity of the N-methyl-D-aspartate (NMDA) glutamate receptor agonist quinolinic acid (QUIN) in the subgenual anterior cingulate cortex (sACC), anterior midcingulate cortex (aMCC) and pregenual anterior cingulate cortex (pACC) of 12 acutely depressed suicidal patients (major depressive disorder/MDD, n = 7; bipolar disorder/BD, n = 5) was analyzed using immunohistochemistry and compared with its expression in 10 healthy control subjects. Results: Depressed patients had a significantly increased density of QUIN-positive cells in the sACC (P = 0.003) and the aMCC (P = 0.015) compared to controls. In contrast, counts of QUIN-positive cells in the pACC did not differ between the groups (P = 0.558). Post-hoc tests showed that significant findings were attributed to MDD and were absent in BD.

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Section: Discussionmentioning

confidence: 99%

Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?

Steiner

Walter

Gos

et al. 2012

Neurology, Psychiatry and Brain Research

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“…Of note, minocycline, a tetracycline derivative, which inhibits the activation of microglia as well as the microglial production of IL-1 and NO, has been shown to inhibit p38 MAPK as well as poly(ADP-ribose) polymerase-1, which along with inhibition of NF-kB (see below), may serve as the basis for its anti-inflammatory efficacy Si et al, 2004;Alano et al, 2006). Interestingly minocycline has also been found to show antidepressant properties in laboratory animals by using the FST both alone and in combination with sub-threshold doses of the tricyclic antidepressant, desipramine, and several glutamate antagonists (Molina-Hernandez et al, 2008). Minocycline has also been shown to inhibit the development of neuroinflammation and behavioral changes after LPS administration (Henry et al, 2008), and has been found to attenuate the development of opioid tolerance, which may in part be related to the capacity of opioids to induce an inflammatory response (Hutchinson et al, 2008a, b;Habibi-Asl et al, 2009).…”

Section: Immunological Targetsmentioning

confidence: 99%

Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior

Haroon

Raison

Miller

2011

Neuropsychopharmacol

837

596

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The potential contribution of chronic inflammation to the development of neuropsychiatric disorders such as major depression has received increasing attention. Elevated biomarkers of inflammation, including inflammatory cytokines and acute-phase proteins, have been found in depressed patients, and administration of inflammatory stimuli has been associated with the development of depressive symptoms. Data also have demonstrated that inflammatory cytokines can interact with multiple pathways known to be involved in the development of depression, including monoamine metabolism, neuroendocrine function, synaptic plasticity, and neurocircuits relevant to mood regulation. Further understanding of mechanisms by which cytokines alter behavior have revealed a host of pharmacologic targets that may be unique to the impact of inflammation on behavior and may be especially relevant to the treatment and prevention of depression in patients with evidence of increased inflammation. Such targets include the inflammatory signaling pathways cyclooxygenase, p38 mitogen-activated protein kinase, and nuclear factor-kB, as well as the metabolic enzyme, indoleamine-2,3-dioxygenase, which breaks down tryptophan into kynurenine. Other targets include the cytokines themselves in addition to chemokines, which attract inflammatory cells from the periphery to the brain. Psychosocial stress, diet, obesity, a leaky gut, and an imbalance between regulatory and pro-inflammatory T cells also contribute to inflammation and may serve as a focus for preventative strategies relevant to both the development of depression and its recurrence. Taken together, identification of mechanisms by which cytokines influence behavior may reveal a panoply of personalized treatment options that target the unique contributions of the immune system to depression.

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“…TNF-α elevation in the microglial cells will subsequently lead to NFκB nuclear translocation which leads to microglial activation by functioning as transcription factor (Figure 7). Minocycline has been previously reported to inhibit the nuclear translocation of NFκB [35,36] in microglia which is one of the rationale for choosing this drug for our study.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide Modified Liposomes for Amyotropic Lateral Sclerosis Therapy: Efficacy in SOD1 Mouse Model

Wiley¹,

Madhankumar²,

Mitchell³

et al. 2012

ANP

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Activation of microglia is a histological feature observed in neurodegenerative diseases like ALS. The oral administration of minocycline has been demonstrated to have minimal neuroprotection ability in the animal models and is also associated with inadvertent toxicity due to non-specific oral absorption of the drug. Nonetheless, the drug itself shows promise in a number of disease models suggesting it could be effective if delivered optimally. Thus, we utilized LPS modified liposomes to target TLR4 receptor on the microglia in SOD1 G93A mice and compared its efficacy with nontargeted nanoliposomes. The in vitro results indicate that targeting the TLR4 receptor on microglia significantly increases (p < 0.01) the uptake of drug by 29% compared to non-targeted liposomes. In the SOD1 G93A mouse model of ALS, targeted and non-targeted minocycline treatment significantly increased (p < 0.05) latency to endpoint stages compared to control mice. Targeting liposomes to microglia significantly delayed disease progression. Both targeted and non-targeted liposomes administration in SOD1 mice resulted in decreased TNF-α secretion in activated BV-2 microglial cells as compared to activated cells receiving no treatment. The non-targeted liposomes had a greater effect than the targeted liposomes in reducing the levels of TNF-α released by the BV-2 cells. In SOD1 G93A mice, the nontargeted nanovesicles significantly increased the latency to rotarod failure and both targeted and non-targeted nanovesicles significantly delayed disease endpoints.

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Antidepressant-like actions of minocycline combined with several glutamate antagonists

Cited by 111 publications

References 59 publications

Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?

Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: Evidence for an immune-modulated glutamatergic neurotransmission?

Psychoneuroimmunology Meets Neuropsychopharmacology: Translational Implications of the Impact of Inflammation on Behavior

Lipopolysaccharide Modified Liposomes for Amyotropic Lateral Sclerosis Therapy: Efficacy in SOD1 Mouse Model

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