Pharmacological modulations of adrenergic phenotype in medullary C2 and C3 cell groups of adult rat

Garcia, Christine; Denoroy, Luc; Cavorsin, Marion Le; Pujol, J.F.; Weissmann, Dinah

doi:10.1016/0891-0618(96)00152-4

Cited by 6 publications

(3 citation statements)

References 53 publications

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“…We observed that in the LC, vindeburnol promotes noradrenaline levels and its metabolism (DOPAC and DA levels) (Figures and ) as well as the level of TH (Figure ), the rate-limiting enzyme in NA biosynthesis, as supported by recent works. Thus, in the rat and mouse LCs, VIND induces a dose-dependent long-term effect on the concentration of TH, − but the stimulation of TH protein expression was independent of the initial activation of noradrenergic neurons as observed by Pujol and co-workers. , To further establish the influence of vindeburnol on TH levels, Weissmann and co-workers determined that treatment with the drug led to an increase in TH protein levels in the rat LC, either through the emergence of new TH-expressing neurons (called “sleeping cells”) or by modulating TH gene expression. , Similar pathways for increasing the TH protein content were observed in the anterior region of the rat nucleus tractus solitarii. − Thus, vindeburnol might improve neuronal plasticity, which contributes to its neuroprotective effects.…”

Section: Resultsmentioning

confidence: 97%

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Antidepressant-like Effect of the Eburnamine-Type Molecule Vindeburnol in Rat and Mouse Models of Ultrasound-Induced Depression

Zubkov,

Riabova,

Zorkina

et al. 2024

ACS Chem. Neurosci.

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Vindeburnol (VIND, RU24722, BC19), a synthetic molecule derived from the eburnamine-vincamine alkaloid group, has many neuropsychopharmacological effects, but its antidepressant-like effects are poorly understood and have only been described in a few patents. To reliably estimate this effect, vindeburnol was studied in a model of long-term variable-frequency ultrasound (US) exposure at 20–45 kHz in male Wistar rats and BALB/c mice. Vindeburnol was administered chronically for 21 days against a background of simultaneous ultrasound exposure at a dose of 20 mg/kg intraperitoneally (IP). Using four behavioral tests, the sucrose preference test (SPT), the social interaction test (SIT), the open field test (OFT), and the forced swimming test (FST), we found that the treatment with the compound diminished depression-like symptoms in mice and rats. The compound restored the ultrasound-related reduced sucrose consumption to control levels and increased social interaction time in mice and rats compared with those in ultrasound-exposed animals. Vindeburnol showed contraversive results of horizontal and vertical activity in both species and generally did not increase locomotor activity. At the same time, the compound showed a specific effect in the FST, significantly reducing the immobility time. Moreover, we found an increase in norepinephrine, dopamine, and its metabolite levels in the brainstem, as well as an increase in dopamine, 3-methoxytyramine, and 3,4-dihydroxyphenylacetic acid levels in the striatum. We also observed a statistically significant increase in tyrosine hydroxylase (TH) levels in the region containing the locus coeruleus (LC). We suggest that using its distinct chemical structure and pharmacological activity as a starting point could boost antidepressant drug discovery.

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Section: Resultsmentioning

confidence: 97%

“…The role of vindeburnol in TH induction is well-documented in the literature. − TH is a key enzyme involved in monoamine metabolism, it may be associated with various neuropsychiatric disorders. We next examined TH protein levels using Western blot analysis in the brain regions of interest: the striatum and LC of BALB/c mice (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Antidepressant-like Effect of the Eburnamine-Type Molecule Vindeburnol in Rat and Mouse Models of Ultrasound-Induced Depression

Zubkov,

Riabova,

Zorkina

et al. 2024

ACS Chem. Neurosci.

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“…Absorption of this antibody with purified bovine PNMT has previously been shown to abolish staining in the medulla (Carlton, Honda, Denoroy, & Willis Jr, ). This antibody has also been used extensively to identify adrenergic neurons in the brains of a variety of species, including rat and human (Carlton, Honda, & Denoroy, ; Garcia, Denoroy, Le Cavorsin, Pujol, & Weissmann, ; Kitahama et al, ; Kitahama, Denoroy, Berod, & Jouvet, ; Mittendorf, Denoroy, & Flugge, ; Siaud, Denoroy, Assenmacher, & Alonso, ). In this study, we found that the antibody showed the expected distribution of PNMT‐immunoreactive cell bodies in the rat medulla.…”

Section: Methodsmentioning

confidence: 99%

Insulin‐responsive autonomic neurons in rat medulla oblongata

Senthilkumaran

Bobrovskaya

Verberne

et al. 2018

J of Comparative Neurology

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Low blood glucose activates brainstem adrenergic and cholinergic neurons, driving adrenaline secretion from the adrenal medulla and glucagon release from the pancreas. Despite their roles in maintaining glucose homeostasis, the distributions of insulin-responsive adrenergic and cholinergic neurons in the medulla are unknown. We fasted rats overnight and gave them insulin (10 U/kg i.p.) or saline after 2 weeks of handling. Blood samples were collected before injection and before perfusion at 90 min. We immunoperoxidase-stained transverse sections of perfused medulla to show Fos plus either phenylethanolamine N-methyltransferase (PNMT) or choline acetyltransferase (ChAT). Insulin injection lowered blood glucose from 4.9 ± 0.3 mmol/L to 1.7 ± 0.2 mmol/L (mean ± SEM; n = 6); saline injection had no effect. In insulin-treated rats, many PNMT-immunoreactive C1 neurons had Fos-immunoreactive nuclei, with the proportion of activated neurons being highest in the caudal part of the C1 column. In the rostral ventrolateral medulla, 33.3% ± 1.4% (n = 8) of C1 neurons were Fos-positive. Insulin also induced Fos in 47.2% ± 2.0% (n = 5) of dorsal medullary C3 neurons and in some C2 neurons. In the dorsal motor nucleus of the vagus (DMV), insulin evoked Fos in many ChAT-positive neurons. Activated neurons were concentrated in the medial and middle regions of the DMV beneath and just rostral to the area postrema. In control rats, very few C1, C2, or C3 neurons and no DMV neurons were Fos-positive. The high numbers of PNMT-immunoreactive and ChAT-immunoreactive neurons that express Fos after insulin treatment reinforce the importance of these neurons in the central response to a decrease in glucose bioavailability.

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Enhanced tail pinch-induced activation of catecholamine metabolism in the pericerulean area of RU 24722-treated rats

Bezin¹,

Ortemann²,

Ogier³

et al. 2004

Brain Research

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Pharmacological modulations of adrenergic phenotype in medullary C2 and C3 cell groups of adult rat

Cited by 6 publications

References 53 publications

Antidepressant-like Effect of the Eburnamine-Type Molecule Vindeburnol in Rat and Mouse Models of Ultrasound-Induced Depression

Antidepressant-like Effect of the Eburnamine-Type Molecule Vindeburnol in Rat and Mouse Models of Ultrasound-Induced Depression

Insulin‐responsive autonomic neurons in rat medulla oblongata

Enhanced tail pinch-induced activation of catecholamine metabolism in the pericerulean area of RU 24722-treated rats

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