Perinatal reduction of functional serotonin transporters results in developmental delay

Kroeze, Yvet; Dirven, Bart; Janssen, Stefan; Kröhnke, Marijke; Barte, Ramona M.; Middelman, Anthonieke; Bokhoven, Hans van; Zhou, Huiqing; Homberg, Judith R.

doi:10.1016/j.neuropharm.2016.05.012

Cited by 28 publications

(32 citation statements)

References 128 publications

(145 reference statements)

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“…The present study demonstrates that reduction of SERT during early development, either by blocking 5-HTT using an SSRI (fluoxetine) or by genetic deletion of SERT, have long-term effects on sensorimotor computation and impairs emergence of adaptive whisking, in agreement with the observations on the serotonergic contributions to motor development (Kroeze et al, 2016). As a result, whisker contacts transmit less mechanical information to whisker follicle.…”

Section: Discussionsupporting

confidence: 90%

“…Changes in the serotonergic drive early in life might have long-term behavioral consequences including depression and anxiety (McAllister et al, 2012;Francis-Oliveira et al, 2013;Kiryanova et al, 2013;Kroeze et al, 2016), deficit in circadian rhythmicity (Kiryanova et al, 2013), reduction in body weight (McAllister et al, 2012;Kroeze et al, 2016), decreased social behavior (Kiryanova et al, 2013), reduced sexual motivation (Kiryanova et al, 2013;Vieira et al, 2013;Rayen et al, 2014), (Kiryanova et al, 2013;Kroeze et al, 2016), and might alter reward processing and learning & memory (Kiryanova et al, 2013). Impaired sensorimotor integration, upon serotonergic dysregulation, might contribute to the expression of many of these phenotypes (Francis-Oliveira et al, 2013;Kroeze et al, 2016). Altered serotonergic drive might also result in miswiring of sensorimotor circuits, and thus cause sensorimotor deficits.…”

Section: Altered Excitation/inhibition Balance Might Explain Serotonementioning

confidence: 99%

“…Emerging evidence suggests that neuromodulator neurotransmitters, in particular serotonin (Schubert et al, 2015), powerfully regulate the development of sensorimotor circuits. Altered serotonergic signaling during early postnatal development impairs the structure and function of neural circuits throughout the brain (Shemer et al, 1991;Whitaker-Azmitia, 1991;Moses-Kolko et al, 2005;Deiró et al, 2006;Pang et al, 2011;Kiryanova et al, 2013;Kroeze et al, 2016), results in anxiety-and depression-like behavior (Olivier et al, 2008;Kiryanova et al, 2013;Kroeze et al, 2016), hinders goal-directed navigation, and impairs object recognition (Kiryanova et al, 2013;Kroeze et al, 2016). Increasing extracellular serotonin availability during development impairs exploration well into adolescence (Kiryanova et al, 2013) while administration of select SSRIs (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Serotonergic development of active sensing

Azarfar

Zhang

Alishbayli

et al. 2019

Preprint

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Active sensing requires adaptive motor (positional) control of sensory organs based on contextual, sensory and task requirements, and develops postnatally after the maturation of intracortical circuits.Alterations in sensorimotor network connectivity during this period are likely to impact sensorimotor computation also in adulthood. Serotonin is among the cardinal developmental regulators of network formation, thus changing the serotonergic drive might have consequences for the emergence and maturation of sensorimotor control. Here we tested this hypothesis on an object localization task by quantifying the motor control dynamics of whiskers during tactile navigation. The results showed that sustained alterations in serotonergic signaling in serotonin transporter knockout rats, or the transient pharmacological inactivation of the transporter during early postnatal development, impairs the emergence of adaptive motor control of whisker position based on recent sensory information. A direct outcome of this altered motor control is that the mechanical force transmitted to whisker follicles upon contact is reduced, suggesting that increased excitability observed upon altered serotonergic signaling is not due to increased synaptic drive originating from the periphery upon whisker contact. These results argue that postnatal development of adaptive motor control requires intact serotonergic signaling and that even its transient dysregulation during early postnatal development causes lasting sensorimotor impairments in adulthood.

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Section: Discussionsupporting

confidence: 90%

Section: Altered Excitation/inhibition Balance Might Explain Serotonementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Serotonergic development of active sensing

Azarfar

Zhang

Alishbayli

et al. 2019

Preprint

Self Cite

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“…The gap crossing task embodies such a stimulus in that the detection of the presence of a platform does not require complex sensory discrimination abilities. This is in sharp contrast to a novel object discrimination task which would involve the ability to discriminate between intricate textures and topologies, which has recently been reported to be impaired in the Sert −/− rat (Kroeze et al 2016). Previous studies have implied impaired tactile performance in Sert −/− mice (Pang et al 2011) and postnatally fluoxetine (SERT inhibitor) exposed rats (Lee 2009).…”

Section: Discussionmentioning

confidence: 66%

Reduced Inhibition within Layer IV of Sert Knockout Rat Barrel Cortex is Associated with Faster Sensory Integration

et al. 2017

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Neural activity is essential for the maturation of sensory systems. In the rodent primary somatosensory cortex (S1), high extracellular serotonin (5-HT) levels during development impair neural transmission between the thalamus and cortical input layer IV (LIV). Rodent models of impaired 5-HT transporter (SERT) function show disruption in their topological organization of S1 and in the expression of activity-regulated genes essential for inhibitory cortical network formation. It remains unclear how such alterations affect the sensory information processing within cortical LIV. Using serotonin transporter knockout (Sert−/−) rats, we demonstrate that high extracellular serotonin levels are associated with impaired feedforward inhibition (FFI), fewer perisomatic inhibitory synapses, a depolarized GABA reversal potential and reduced expression of KCC2 transporters in juvenile animals. At the neural population level, reduced FFI increases the excitatory drive originating from LIV, facilitating evoked representations in the supragranular layers II/III. The behavioral consequence of these changes in network excitability is faster integration of the sensory information during whisker-based tactile navigation, as Sert−/− rats require fewer whisker contacts with tactile targets and perform object localization with faster reaction times. These results highlight the association of serotonergic homeostasis with formation and excitability of sensory cortical networks, and consequently with sensory perception.

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“…Anxiolytic and antidepressant effects of EHP in the F1 generation coming from mothers treated during pregnancy, as well as the absence of neuromotor and memory changes in neonatal rats were described by Campos and coworkers (unpublished data). The assessment of the effects of EHP in the F1 generation is important for verifying toxicity and aims to contribute to the safe use of this herbal medicine for pregnant women, because its physiological action through the activation of CNS receptors opioids (Schuurmans et al, 2015), serotonergic drugs (Kroeze et al, 2016), noradrenergic drugs (Murrin et al, 2007) and GABAergic drugs (Xia and Haddad, 1992), may interfere with neurodevelopment (Kroeze et al, 2016). This action can occur by different mechanisms and pathways, through the control of apoptosis, mitosis, cell differentiation, dendritogenesis and synaptogenesis in different stages of life and places, but especially in areas related to pain control and seizures (Brunton et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Effect of the extract of Hypericum perforatum on neurodevelopment of regions related to pain control and convulsion

Campos¹,

Guerra²,

Peters³

et al. 2017

J. Med. Plants Res.

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Hypericum perforatum (HP) is well-known by the population of the world as herb with antidepressant effect. Its various components, such as hypericin and hyperforin, provide many other effects for this plant, for example, antinociceptive and anticonvulsant. The aim of this work was to determine whether HP administration during pregnancy can cause changes in neurodevelopment related to pain control and seizures in rats (F1). For this, Wistar rats received oral doses of HP at 36, 72 and 144 mg/kg throughout pregnancy. Tests to evaluate the antinociceptive and anticonvulsant activity of HP were performed in adult F1 rats, which showed a decrease of both responses, suggesting therefore that HP exposition during pregnancy causes changes in neurodevelopment of brain regions related to pain control and seizures in rats.

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Perinatal reduction of functional serotonin transporters results in developmental delay

Cited by 28 publications

References 128 publications

Serotonergic development of active sensing

Serotonergic development of active sensing

Reduced Inhibition within Layer IV of Sert Knockout Rat Barrel Cortex is Associated with Faster Sensory Integration

Effect of the extract of Hypericum perforatum on neurodevelopment of regions related to pain control and convulsion

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