The many different faces of major depression: It is time for personalized medicine

Korte, S. Mechiel; Prins, Jolanda; Krajnc, Anne M.; Hendriksen, Erik; Oosting, Ronald S.; Westphal, Koen G.C.; Korte-Bouws, G.A.H.; Olivier, Berend

doi:10.1016/j.ejphar.2014.11.045

Cited by 46 publications

(27 citation statements)

References 207 publications

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“…The observed hippocampal reduction in GluA2 expression within long-thin and mushroom spines, along with a concomitant increase in TH and DAT represents potential dysfunction associated with mood-related illnesses, such as depression (Korte et al., 2015, Lodge and Grace, 2011). Antidepressants have been found to rescue AMPA dysfunction in chronically stressed animals (Kallarackal et al., 2013) and further increase AMPA phosphorylation and surface expression (Martinez-Turrillas et al., 2002, Svenningsson et al., 2002).…”

Section: Discussionmentioning

confidence: 99%

Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

Iñiguez

Aubry

Riggs

et al. 2016

Neurobiology of Stress

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Social stress, including bullying during adolescence, is a risk factor for common psychopathologies such as depression. To investigate the neural mechanisms associated with juvenile social stress-induced mood-related endophenotypes, we examined the behavioral, morphological, and biochemical effects of the social defeat stress model of depression on hippocampal dendritic spines within the CA1 stratum radiatum. Adolescent (postnatal day 35) male C57BL/6 mice were subjected to defeat episodes for 10 consecutive days. Twenty-four h later, separate groups of mice were tested on the social interaction and tail suspension tests.Hippocampi were then dissected and Western blots were conducted to quantify protein levels for various markers important for synaptic plasticity including protein kinase M zeta (PKMζ), protein kinase C zeta (PKCζ), the dopamine-1 (D1) receptor, tyrosine hydroxylase (TH), and the dopamine transporter (DAT). Furthermore, we examined the presence of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-receptor subunit GluA2 as well as colocalization with the post-synaptic density 95 (PSD95) protein, within different spine subtypes (filopodia, stubby, long-thin, mushroom) using an immunohistochemistry and Golgi-Cox staining technique. The results revealed that social defeat induced a depression-like behavioral profile, as inferred from decreased social interaction levels, increased immobility on the tail suspension test, and decreases in body weight. Whole hippocampal immunoblots revealed decreases in GluA2, with a concomitant increase in DAT and TH levels in the stressed group. Spine morphology analyses further showed that defeated mice displayed a significant decrease in stubby spines, and an increase in long-thin spines within the CA1 stratum radiatum. Further evaluation of GluA2/PSD95 containing-spines demonstrated a decrease of these markers within long-thin and mushroom spine types. Together, these results indicate that juvenile social stress induces GluA2- and dopamine-associated dysregulation in the hippocampus – a neurobiological mechanism potentially underlying the development of mood-related syndromes as a consequence of adolescent bullying.

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Section: Discussionmentioning

confidence: 99%

Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

Iñiguez

Aubry

Riggs

et al. 2016

Neurobiology of Stress

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“…Following the introduction of the selective serotonin reuptake inhibitors (SSRI), hypotheses emerged that altering serotonergic neurotransmission, via the transmitter and/or its receptors, made them more “selective” for MDD or specific MDD subtypes [10]. With the advent of serotonin-norepinephrine reuptake inhibitors and triple (serotonin, norepinephrine, dopamine) reuptake inhibitors [11], manufacturers speculated that such “broad-spectrum” actions made these antidepressants preferable for certain depressed patients [12]. …”

Section: What Is the Therapeutic Action Of Antidepressants?mentioning

confidence: 99%

What Is New about New Antidepressants?

Dubovsky¹

2018

Psychother Psychosom

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“…This neurobiology forms the basis for the action of important pharmaceuticals, including synthetic PAA derivatives such as the antidepressant bupropion (e.g. Wellbutrin) (2) and amphetamine-containing attention deficit disorder treatments (e.g. Adderall and Dexedrine) (3).…”

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confidence: 99%

An N-methyltransferase from Ephedra sinica catalyzing the formation of ephedrine and pseudoephedrine enables microbial phenylalkylamine production

Morris

Groves

Hagel

et al. 2018

Journal of Biological Chemistry

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Phenylalkylamines, such as the plant compounds ephedrine and pseudoephedrine and the animal neurotransmitters dopamine and adrenaline, compose a large class of natural and synthetic molecules with important physiological functions and pharmaceutically valuable bioactivities. The final steps of ephedrine and pseudoephedrine biosynthesis in members of the plant genus involve-methylation of norephedrine and norpseudoephedrine, respectively. Here, using a plant transcriptome screen, we report the isolation and characterization of an -methyltransferase (NMT) from able to catalyze the formation of (pseudo)ephedrine and other naturally occurring phenylalkylamines, including -methylcathinone and-methyl(pseudo)ephedrine. Phenylalkylamine -methyltransferase (PaNMT) shares substantial amino acid sequence identity with enzymes of the NMT family involved in benzylisoquinoline alkaloid (BIA) metabolism in members of the higher plant order Ranunculales, which includes opium poppy (). PaNMT accepted a broad range of substrates with phenylalkylamine, tryptamine, β-carboline, tetrahydroisoquinoline, and BIA structural scaffolds, which is in contrast to the specificity for BIA substrates of NMT enzymes within the Ranunculales. PaNMT transcript levels were highest in young shoots of , which corresponded to the location of NMT activity yielding (pseudo)ephedrine,-methylcathinone, and -methyl(pseudo)ephedrine, and with accumulation of phenylalkylamines. Co-expression of recombinant genes encoding PaNMT and an ω-transaminase (PP2799) from in enabled the conversion of exogenous ()-phenylacetylcarbinol (PAC) and ()-PAC to ephedrine and pseudoephedrine, respectively. Our work further demonstrates the utility of plant biochemical genomics for the isolation of key enzymes that facilitate microbial engineering for the production of medicinally important metabolites.

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The many different faces of major depression: It is time for personalized medicine

Cited by 46 publications

References 207 publications

Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

Social defeat stress induces depression-like behavior and alters spine morphology in the hippocampus of adolescent male C57BL/6 mice

What Is New about New Antidepressants?

An N-methyltransferase from Ephedra sinica catalyzing the formation of ephedrine and pseudoephedrine enables microbial phenylalkylamine production

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