Demonstration of decreased activity of dorsal raphe nucleus neurons in depressed suicidal patients by the AgNOR staining method

Gos, Tomasz; Krell, Dieter; Brisch, Ralf; Bielau, Hendrik; Trübner, Kurt; Steiner, Johann; Bernstein, Hans‐Gert; Bogerts, Bernhard

doi:10.1016/j.jad.2008.03.002

Cited by 29 publications

(35 citation statements)

References 63 publications

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“…Our previous studies suggested the decreased rDNA transcriptional activity in DRN neurons in depressed suicidal compared to non-suicidal individuals [4, 24]. These results seem to be complementary to our current findings, as the increased microglia activity observed in the DRN of depressed suicides versus non-suicides may result in the decreased rDNA transcription in the former subgroup.…”

Section: Discussionsupporting

confidence: 89%

“…The observed effect was neither confounded by other variables, among them postmortem interval, nor related to psychotropic medication, which partially counteracted this effect. The significance was shown in the cumulative analysis of all DRN subnuclei, i.e., similarly as in our previous AgNOR studies [4, 5, 24, 39]. This phenomenon could be related to the functional characteristics of DRN subregions, as their connections overlap in target structures [7–9] in spite of the accentuated distinctiveness [48, 49].…”

Section: Discussionsupporting

confidence: 85%

“…The tissue preparation was performed as previously described [4, 24, 39]. Briefly, brains were fixed in toto in 8% phosphate-buffered formaldehyde for at least 2 months (pH = 7.0; temperature 15–20 °C).…”

Section: Introductionmentioning

confidence: 99%

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Microglia in the dorsal raphe nucleus plays a potential role in both suicide facilitation and prevention in affective disorders

Brisch

Steiner

Mawrin

et al. 2017

Eur Arch Psychiatry Clin Neurosci

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An involvement of the central serotonergic system has constantly been reported in the pathogenesis of suicide. The dorsal raphe nucleus (DRN) is the main source of serotonergic innervation of forebrain limbic structures disturbed in suicidal behaviour, in which an abnormal microglia reaction seems to play a role. In our present study, the density of microglia immunostained for the HLA-DR antigen was evaluated in the DRN. These analyses were carried out on paraffin-embedded brains from 24 suicidal and 21 non-suicidal patients; among them, 27 depressed (15 major depressive disorder and 12 bipolar disorder) and 18 schizophrenia (9 residual and 9 paranoid) patients and 22 matched controls without mental disorders. Only the non-suicidal depressed subgroup revealed significantly lower microglial reaction, i.e., a decreased density of HLA-DR positive microglia versus both depressed suicide victims and controls. The effect was not related to antidepressant or antipsychotic medication, as the former correlated positively with microglial density in non-suicidal depressed patients, and the latter had no effect. Moreover, the comparison of these results with previously published data from our workgroup in the same cohort (Krzyżanowska et al. in Psychiatry Res 241:43–46, 4) suggested a positive impact of microglia on ribosomal DNA transcription in DRN neurons in the non-suicidal depressed subgroup, but not in depressed suicidal cases. Therefore, the interaction between microglia and neurons in the DRN may be potentially involved in opposite ways regarding suicide facilitation and prevention in the tested subgroups of depressed patients.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 85%

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Microglia in the dorsal raphe nucleus plays a potential role in both suicide facilitation and prevention in affective disorders

Brisch

Steiner

Mawrin

et al. 2017

Eur Arch Psychiatry Clin Neurosci

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“…Increased floating behavior in the FST upon decreasing r1 5-HTergic activity is in line with decreased floating behavior after increasing DR 5-HT activity (Veerakumar et al, 2014; Warden et al, 2012) and supports a causal relationship of low DR 5-HTergic neuronal activity with depression-like behavior (Bambico et al, 2009; Gos et al, 2008; Jacobsen et al, 2012; Lira et al, 2003). In addition, decreased floating behavior upon decreasing r2 5-HTergic activity also confirms a direct causal relationship that was previously only suggested (Almeida et al, 2013).…”

Section: Discussionsupporting

confidence: 64%

“…This finding is surprising considering decreased DR 5-HTergic activity in mouse models of depressive-like behavior (Bambico et al, 2009; Lira et al, 2003; Veerakumar et al, 2014) and suggestive evidence for decreased 5-HT signaling in depressed patients (Blier et al, 1990; Gos et al, 2008). Furthermore, genetic models with a life-long decrease in 5-HT levels display increased depression-like behaviors and decreased anxiety (Kim et al, 2009; Kiyasova et al, 2011; Mosienko et al, 2012; Narboux-Nême et al, 2011).…”

Section: Discussionmentioning

confidence: 95%

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors

Teissier

Chemiakine

Inbar³

et al. 2015

Cell Reports

166

140

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SUMMARY Despite the well-established role of serotonin signaling in mood regulation, causal relationships between serotonergic neuronal activity and behavior remain poorly understood. Using a pharmacogenetic approach, we find that selectively increasing serotonergic neuronal activity in wild-type mice is anxiogenic and reduces floating in the forced-swim-test, while inhibition has no effect on the same measures. In a developmental mouse model of altered emotional behavior, increased anxiety and depression-like behaviors correlate with reduced dorsal raphe and increased median raphe serotonergic activity. These mice display blunted responses to serotonergic stimulation and behavioral rescues through serotonergic inhibition. We furthermore identify opposing consequences of dorsal versus median raphe serotonergic neuron inhibition on floating behavior, together suggesting that median raphe hyperactivity increases anxiety, while a low dorsal/median raphe serotonergic activity ratio increases depression-like behavior. Thus we find a critical role of serotonergic neuronal activity in emotional regulation and uncover opposing roles of median and dorsal raphe function.

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Effect of buscopan, a compound that alleviates cramps, on the developing nervous system of the chick embryo

Ertekin

Atay

Bozkurt

et al. 2021

Birth Defects Research

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Background Buscopan is used to treat stomach cramps including those resulting from irritable bowel syndrome, bladder cramps, and pain related to menstruation. Its pregnancy category is determined as C. It has been shown in experimental animal studies that the drug has a negative effect on the embryo, but sufficient and well‐controlled studies have not been conducted in humans. The aim of this study is to investigate effects of buscopan on the development of the neural tube (NT) in chick embryos. Methods Sixty specific pathogen‐free (SPF) fertilized eggs were used. SPF eggs were placed in an incubator and divided into six groups at 28 hr of incubation. Five different doses (low to high) of buscopan were injected sub‐blastodermally. At the end of 48 hr, the embryos were evaluated morphologically and histopathologically. The argyrophilic nucleolar‐organizing region (AgNOR) method was used in this study to determine the proliferation activity of cells in NT development in chick embryos. AgNOR number and total AgNOR area/nuclear area (TAA/NA) were detected for each embryo. Results Depending on the dose, the embryo's crown‐rump length and somite number decreased (p < .05). Significant differences were detected among all groups for mean AgNOR number (p < .05) and TAA/NA ratio (p < .05). Conclusions Considering the average count of AgNOR cells and TAA/NA ratio, it was found that there was a decrease in cell division depending on the dose. It was determined that buscopan treatment on chick embryos adversely affected early nervous system and NT development.

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Demonstration of decreased activity of dorsal raphe nucleus neurons in depressed suicidal patients by the AgNOR staining method

Cited by 29 publications

References 63 publications

Microglia in the dorsal raphe nucleus plays a potential role in both suicide facilitation and prevention in affective disorders

Microglia in the dorsal raphe nucleus plays a potential role in both suicide facilitation and prevention in affective disorders

Activity of Raphé Serotonergic Neurons Controls Emotional Behaviors

Effect of buscopan, a compound that alleviates cramps, on the developing nervous system of the chick embryo

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