Old neurochemical markers, new functional directions?

Deurwaerdère, Philippe De; Gaetani, Silvana; Vaughan, Roxanne A.

doi:10.1111/jnc.14929

Cited by 9 publications

(3 citation statements)

References 13 publications

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“…The study with the correlations of neurotransmitter content between pairs of brain regions can inform about modified relationships of the content of neurotransmitters at terminals in brain regions (Fitoussi et al, 2013;Dellu-Hagedorn et al, 2017;Puginier et al, 2019;De Deurwaerdere et al, 2020b). Tissue content mostly represents the content of neurotransmitters contained in vesicles of exocytosis while the cytoplasmic content and the extrasynaptic levels would poorly contribute to the total tissue content (Eisenhofer et al, 2004), representing for DA in the striatum 3% and negligible content of total DA, respectively (Pregeljc et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Lorcaserin Alters Serotonin and Noradrenaline Tissue Content and Their Interaction With Dopamine in the Rat Brain

et al. 2020

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Lorcaserin is a preferential serotonin2C receptor (5-HT 2C R) agonist effective to treat obesity that has also recently been proposed to treat addiction and epilepsy. Central dopamine (DA) mechanisms are likely involved in the lorcaserin mechanism of action, but other monoamines 5-HT and noradrenaline (NA) contents or their interaction with DA might account for its effects. Here we showed that lorcaserin at 3, but not 0.3 mg/kg enhanced 5-HT content in the insular cortex, the core of the nucleus accumbens, and ventral hypothalamus. Without affecting the metabolite 5-hydroxy indole acetic acid, lorcaserin reduced the indirect index of 5-HT turnover in the hippocampus, substantia nigra, and habenula. Lorcaserin at 3 mg/kg increased NA content in the orbitofrontal cortex, the central amygdala (also at 0.3 mg/kg), the ventral hypothalamus, and the shell of the nucleus accumbens. A correlative analysis of the tissue contents between pairs of brain regions revealed that 0.3 mg/kg lorcaserin enhanced the number of correlations for 5-HT, its metabolism, and NA to a lower extent. The correlation profiles were very different between saline, 0.3 and 3 mg/kg lorcaserin. Lorcaserin enhanced the correlations established between NA or 5-HT at 0.3 and 3 mg/kg and reduced the number of correlations established between the index of the turnover for DA and 5-HT. These results show that lorcaserin modulates the biochemistry of NA and 5-HT systems in a subset of brain regions. Qualitatively, they reveal, oppositely to the DA changes, that lorcaserin at 0.3, but not 3 mg/kg, enhanced the number of correlations of 5-HT content between brain regions.

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Section: Discussionmentioning

confidence: 99%

Lorcaserin Alters Serotonin and Noradrenaline Tissue Content and Their Interaction With Dopamine in the Rat Brain

et al. 2020

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“…Neurochemical measurements for 5-HT, DA, and NE, as well as select metabolites (5-HIAA, DOPAC, HVA, SAL) were corrected for the weight of each sample (i.e., µg of neurochemical/gram of tissue) ± standard error of mean. The ratio of metabolite to neurotransmitter (5-HIAA/5-HT; DOPAC + HVA/DA) was calculated as a measure of neurotransmitter turnover ( NJ et al, 1986 ; Peneder et al, 2011 ; Deurwaerdere et al, 2020 ; Bauer et al, 2021 ).…”

Section: Methodsmentioning

confidence: 99%

An evaluation of the rat intestinal monoamine biogeography days following exposure to acute stress

2022

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Stress-induced abnormalities in gut monoamine levels (e.g., serotonin, dopamine, norepinephrine) have been linked to gastrointestinal (GI) dysfunction, as well as the worsening of symptoms in GI disorders. However, the influence of stress on changes across the entire intestinal monoamine biogeography has not been well-characterized, especially in the days following stress exposure. Therefore, the aim of this study was to comprehensively assess changes to monoamine neurochemical signatures across the entire rat intestinal tract days after exposure to an acute stressor. To the end, adult male F344 rats were subjected to an episode of unpredictable tail shocks (acute stress) or left undisturbed. Forty-eight hours later rats were euthanized either following a 12 h period of fasting or 30 min of food access to evaluate neurochemical profiles during the peri- and early postprandial periods. Monoamine-related neurochemicals were measured via UHPLC in regions of the small intestine (duodenum, jejunum, ileum), large intestine (cecum, proximal colon, distal colon), cecal contents, fecal contents, and liver. The results suggest a relatively wide-spread increase in measures of serotonin activity across intestinal regions can be observed 48 h after exposure to acute stress, however some evidence was found supporting localized differences in serotonin metabolization. Moreover, acute stress exposure reduced catecholamine-related neurochemical concentrations most notably in the ileum, and to a lesser extent in the cecal contents. Next, stress-related fecal serotonin concentrations were consistent with intestinal profiles. However, fecal dopamine was elevated in association with stress, which did not parallel findings in any other intestinal area. Finally, stress exposure and the food access period together only had minor effects on intestinal monoamine profiles. Taken together, these data suggest nuanced differences in monoaminergic profiles exist across intestinal regions the days following exposure to an acute stressor, highlighting the importance of assessments that consider the entire intestinal tract biogeography when investigating stress-related biological outcomes that may be relevant to GI pathophysiology.

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“…It forms the origin of direct-indirect pathways, which are distinct basal ganglia circuits involved in motor control (37). The dorsal striatum handles the input -output of many functions, for example, motor activity (38). The plasticity of the striatum might be related to adaptive motor control and procedural memory (37).…”

Section: Figure 2 |mentioning

confidence: 99%

Metabolic Brain Network Analysis With 18F-FDG PET in a Rat Model of Neuropathic Pain

et al. 2021

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Neuropathic pain has been found to be related to profound reorganization in the function and structure of the brain. We previously demonstrated changes in local brain activity and functional/metabolic connectivity among selected brain regions by using neuroimaging methods. The present study further investigated large-scale metabolic brain network changes in 32 Sprague–Dawley rats with right brachial plexus avulsion injury (BPAI). Graph theory was applied in the analysis of 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG) PET images. Inter-subject metabolic networks were constructed by calculating correlation coefficients. Global and nodal network properties were calculated and comparisons between pre- and post-BPAI (7 days) status were conducted. The global network properties (including global efficiency, local efficiency and small-world index) and nodal betweenness centrality did not significantly change for all selected sparsity thresholds following BPAI (p > 0.05). As for nodal network properties, both nodal degree and nodal efficiency measures significantly increased in the left caudate putamen, left medial prefrontal cortex, and right caudate putamen (p < 0.001). The right entorhinal cortex showed a different nodal degree (p < 0.05) but not nodal efficiency. These four regions were selected for seed-based metabolic connectivity analysis. Strengthened connectivity was found among these seeds and distributed brain regions including sensorimotor area, cognitive area, and limbic system, etc. (p < 0.05). Our results indicated that the brain had the resilience to compensate for BPAI-induced neuropathic pain. However, the importance of bilateral caudate putamen, left medial prefrontal cortex, and right entorhinal cortex in the network was strengthened, as well as most of their connections with distributed brain regions.

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Old neurochemical markers, new functional directions?

Cited by 9 publications

References 13 publications

Lorcaserin Alters Serotonin and Noradrenaline Tissue Content and Their Interaction With Dopamine in the Rat Brain

Lorcaserin Alters Serotonin and Noradrenaline Tissue Content and Their Interaction With Dopamine in the Rat Brain

An evaluation of the rat intestinal monoamine biogeography days following exposure to acute stress

Metabolic Brain Network Analysis With 18F-FDG PET in a Rat Model of Neuropathic Pain

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