Behavioral and molecular effects of prenatal continuous light exposure in the adult rat

Voiculescu, Suzana Elena; Duc, Diana Le; Roşca, Adrian Eugen; Zeca, Vlad; Chiţimuș, Diana Maria; Arsene, Andreea Letiția; Drăgoi, Cristina Manuela; Nicolae, Alina; Zăgrean, Leon; Schöneberg, Torsten; Zăgrean, Ana‐Maria

doi:10.1016/j.brainres.2016.08.031

Cited by 40 publications

(43 citation statements)

References 58 publications

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“…Hippocampus has a high density of melatonin receptors (Lacoste et al, 2015; Musshoff et al, 2002). Voiculescu et al (2016) demonstrated that prenatal continuous light exposure causes anxiety‐like behavior, impairment of short‐term memory, decreased levels of melatonin and serotonin, and melatonin signaling dysregulation, as well as, increased chronic oxidative stress in prenatal continuous light exposure offspring. Vilches et al (2014) demonstrated that hippocampus of fetuses gestated under light: dark photoperiod (12:12) displayed daily oscillatory expression of the clock genes Bmal1 and Per2, clock‐controlled genes Mtnr1b, Slc2a4, Nr3c1 and NMDA receptor subunits 1B‐3A‐3B.…”

Section: Discussionmentioning

confidence: 99%

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The neuroprotective role of melatonin in a gestational hypermethioninemia model

Figueiró¹,

Moreira²,

Santos³

et al. 2019

Intl J of Devlp Neuroscience

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Elevated levels of methionine in blood characterize the hypermethioninemia, which may have genetic or non‐genetic origin, as for example from high protein diet. Born rats from hypermethioninemic mothers presented cerebral oxidative stress, inhibition of Na+,K+‐ATPase, memory deficit and ultrastructure cerebral changes. Melatonin is a hormone involved in circadian rhythm and has antioxidant effects. The aim of this study was to verify the possible neuroprotective effects of melatonin administration in hypermethioninemic pregnant rats on damage to biomolecules (Na+,K+‐ATPase, sulfhydryl content and DNA damage index) and behavior (open field, novel object recognition and water maze tasks), as well as its effect on cells morphology by electron microscopy in offspring. Wistar female rats received methionine (2.68 μmol/g body weight) and/or melatonin (10 mg/kg body weight) by subcutaneous injections during entire pregnancy. Control rats received saline. Biochemical analyzes were performed at 21 and 30 days of life of offspring and behavioral analyzes were performed only at 30 days of age in male pups. Results showed that gestational hypermethioninemia diminished Na+,K+‐ATPase activity and sulfhydryl content and increased DNA damage at 21 and 30 days of life. Melatonin was able to totally prevent Na+,K+‐ATPase activity alteration at 21 days and partially prevent its alteration at 30 days of rats life. Melatonin was unable in to prevent sulfhydryl and DNA damage at two ages. It also improved DNA damage, but not at level of saline animals (controls). Regarding to behavioral tests, data showed that pups exposed to gestational hypermethioninemia decreased reference memory in water maze, spent more time to the center of the open field and did not differentiate the objects in the recognition test. Melatonin was able to prevent the deficit in novel object recognition task. Electron microscopy revealed ultrastructure alterations in neurons of hypermethioninemic at both ages of offspring, whose were prevented by melatonin. These findings suggest that melatonin may be a good neuroprotective to minimize the harmful effects of gestational hypermethioninemia on offspring.

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Section: Discussionmentioning

confidence: 99%

“…Hippocampus has a high density of melatonin receptors (Lacoste et al, 2015;Musshof et al, 2002). Voiculescu et al (2016) demonstrated that prenatal continuous light exposure causes anxiety-like Fig. 8.…”

Section: Figmentioning

confidence: 99%

The neuroprotective role of melatonin in a gestational hypermethioninemia model

Figueiró¹,

Moreira²,

Santos³

et al. 2019

Intl J of Devlp Neuroscience

View full text Add to dashboard Cite

show abstract

“…In support of this, it has been reported that offspring of animals were exposed to altered light/dark cycles at the last stage of gestation and thus had their pineal melatonin synthesis abolished, present several molecular, and behavioral alterations in the adulthood. In particular, expression of molecules related to neurotransmitter signaling, such as NMDA receptor subunits Grin1b/Grin3a as well as the serotonin reuptaker Slc6a4 , is reduced in the adult offspring of rats that were exposed to constant light during pregnancy. These animals also displayed anxiety‐ and depressive‐like behavior in the adulthood …”

Section: Discussionmentioning

confidence: 99%

“…In particular, expression of molecules related to neurotransmitter signaling, such as NMDA receptor subunits Grin1b/Grin3a as well as the serotonin reuptaker Slc6a4 , is reduced in the adult offspring of rats that were exposed to constant light during pregnancy. These animals also displayed anxiety‐ and depressive‐like behavior in the adulthood …”

Section: Discussionmentioning

confidence: 99%

The role of melatonin in the neurodevelopmental etiology of schizophrenia: A study in human olfactory neuronal precursors

Galván-Arrieta

Trueta²,

Cercós³

et al. 2017

Journal of Pineal Research

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Dim light exposure of the mother during pregnancy has been proposed as one of the environmental factors that affect the fetal brain development in schizophrenia. Melatonin circulating levels are regulated by the environmental light/dark cycle. This hormone stimulates neuronal differentiation in the adult brain. However, little is known about its role in the fetal human brain development. Olfactory neuronal precursors (ONPs) are useful for studying the physiopathology of neuropsychiatric diseases because they mimic all the stages of neurodevelopment in culture. Here, we first characterized whether melatonin stimulates neuronal differentiation in cloned ONPs obtained from a healthy control subject (HCS). Then, melatonin effects were evaluated in primary cultures of ONPs derived from a patient diagnosed with schizophrenia (SZ) and an age- and gender-matched HCS. Axonal formation was evidenced morphologically by tau immunostaining and by GSK3β phosphorylated state. Potassium-evoked secretion was assessed as a functional feature of differentiated neurons. As well, we report the expression of MT1/2 receptors in human ONPs for the first time. Melatonin stimulated axonal formation and ramification in cloned ONPs through a receptor-mediated mechanism and enhanced the amount and velocity of axonal and somatic secretion. SZ ONPs displayed reduced axogenesis associated with lower levels of pGSK3β and less expression of melatonergic receptors regarding the HCS ONPs. Melatonin counteracted this reduction in SZ cells. Altogether, our results show that melatonin signaling is crucial for functional differentiation of human ONPs, strongly suggesting that a deficit of this indoleamine may lead to an impaired neurodevelopment which has been associated with the etiology of schizophrenia.

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“…Previous studies have indicated that melatonin may have oncostatic properties by altering the angiogenic mechanisms or metastatic and proliferative properties of a number of cancer types, including OSCC (10)(11)(12). Melatonin (N-acetyl-5methoxytryptamine) is an indolic compound primarily secreted by the pineal gland in response to darkness signals (13)(14)(15), although small amounts may be excreted by the retina, the gastrointestinal tract, the skin, the bone marrow (16) and the salivary glands (17). Isola and Lilliu (18) analyzed fragments of salivary glands obtained from male patients undergoing oral tumor resection surgery and demonstrated melatonin subcellular localization in the significant human salivary gland parenchyma (parotid, submandibular and sublingual).…”

Section: Introductionmentioning

confidence: 99%

Clinical significance of serum melatonin in predicting the severity of oral squamous cell carcinoma

et al. 2019

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Melatonin, the primary hormone produced by the pineal gland, is intensely assessed for its anticancer properties. This study aimed to reveal the clinical significance of serum melatonin levels in predicting the severity of oral squamous cell carcinoma (OSCC). For this purpose, 40 male patients with OSCC and 30 healthy subjects were enrolled in this study. The serum levels of melatonin were determined by ELISA. The results revealed that the melatonin concentrations were significantly lower in the patients with OSCC compared with the controls (18.2 vs. 47.6 pg/ml, P<0.001). In addition, the serum melatonin levels had a high predictive accuracy for discriminating patients with OSCC with T-depth of invasion (DOI) II from the healthy controls (89.1%), as well as in discriminating patients with OSCC with nodal metastasis from those without nodal metastasis (83.8%). On the whole, the findings of this study suggest that the serum melatonin concentrations are closely related to the severity of OSCC and may thus be used to assess the different stages of oral cancer objectively and accurately. The present study also supports the conclusion that melatonin may be a potential therapeutic agent for use in the treatment of patients with OSCC.

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Behavioral and molecular effects of prenatal continuous light exposure in the adult rat

Cited by 40 publications

References 58 publications

The neuroprotective role of melatonin in a gestational hypermethioninemia model

The neuroprotective role of melatonin in a gestational hypermethioninemia model

The role of melatonin in the neurodevelopmental etiology of schizophrenia: A study in human olfactory neuronal precursors

Clinical significance of serum melatonin in predicting the severity of oral squamous cell carcinoma

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