Altered serotonin innervation in the rat epileptic brain

Maia, Gisela H.; Soares, Joana I.; Almeida, Sérgio G.; Leite, Jose O; Baptista, Helena X.; Lukoyanova, Alisa N.; Brazete, Cátia; Lukoyanov, Nikolay

doi:10.1016/j.brainresbull.2019.07.009

Cited by 20 publications

(13 citation statements)

References 81 publications

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“…For instance, the fine 5-HT axon terminals are supposed to be extremely vulnerable to psychotropic drugs like amphetamine (O'Hearn, Battaglia, De Souza, Kuhar, & Molliver, 1988). Similarly, change in the ratio of these fiber types has been observed in epilepsy where fibers with small-sized varicosities were decreased in the dentate gyrus of hippocampus, infralimbic cortex, and MS while that of the fibers with larger-sized varicosities were increased (Maia et al, 2019). Moreover, changes in the morphology of serotonergic fibers associated with aging have been reported (Nishimura et al, 1998).…”

Section: Discussionmentioning

confidence: 94%

Comprehensive topographical map of the serotonergic fibers in the male mouse brain

Awasthi

Tamada

Overton

et al. 2020

J of Comparative Neurology

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It is well established that serotonergic fibers distribute throughout the brain. Abnormal densities or patterns of serotonergic fibers have been implicated in neuropsychiatric disorders. Although many classical studies have examined the distribution pattern of serotonergic fibers, most of them were either limited to specific brain areas or had limitations in demonstrating the fine axonal morphology. In this study, we utilize male mice expressing green fluorescence protein under the serotonin transporter (SERT) promoter to map the topography of serotonergic fibers across the rostro-caudal extent of each brain area. We demonstrate previously unreported regional density and fine-grained anatomy of serotonergic fibers. Our findings include: (a) SERT fibers distribute abundantly in the thalamic nuclei close to the midline and dorsolateral areas, in most of the hypothalamic nuclei with few exceptions such as the median eminence and arcuate nuclei, and within the basal amygdaloid complex and lateral septal nuclei, (b) the source fibers of innervation of the hippocampus traverse through the septal nuclei before reaching its destination, (c) unique, filamentous type of straight terminal fibers within the nucleus accumbens, (d) laminar pattern of innervation in the hippocampus, olfactory bulb and cortex with heterogenicity in innervation density among the layers, (e) cortical labeling density gradually decreases rostro-caudally, (f) fibers traverse and distribute mostly within the gray matter, leaving the white fiber bundles uninnervated, and (g) most of the highly labeled nuclei and cortical areas have predominant anatomical connection to limbic structures. In conclusion, we provide novel, regionally specific insights on the distribution map of serotonergic fibers using transgenic mouse.

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Section: Discussionmentioning

confidence: 94%

Comprehensive topographical map of the serotonergic fibers in the male mouse brain

Awasthi

Tamada

Overton

et al. 2020

J of Comparative Neurology

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“…For a long time, the link between epilepsy and mental disorders has been attributed exclusively to the serotonergic system. Several studies, in fact, have shown how an epilepsy animal model displayed alterations in serotonergic system both in terms of release of serotonin and of deficit in pre/post synaptic transmission of serotonergic neurons (89)(90)(91). The connection between noradrenaline and serotonin deficiencies and epilepsy have been found also in humans.…”

Section: Discussionmentioning

confidence: 99%

Polyamines: The possible missing link between mental disorders and epilepsy (Review)

et al. 2019

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Polyamines are small positively charged alkylamines that are essential in a number of crucial eukaryotic processes, like normal cell growth and development. In normal physiological conditions, intracellular polyamine content is tightly regulated through a fine regulated network of biosynthetic and catabolic enzymes and a transport system. The dysregulation of this network is frequently associated to different tumors, where high levels of polyamines has been detected. Polyamines also modulate ion channels and ionotropic glutamate receptors and altered levels of polyamines have been observed in different brain diseases, including mental disorders and epilepsy. The goal of this article is to review the role of polyamines in mental disorders and epilepsy within a frame of the possible link between these two brain pathologies. The high comorbidity between these two neurological illnesses is strongly suggestive that they share a common background in the central nervous system. This review proposes an additional association between the noradrenalin/serotonin and glutamatergic neuronal circuits with polyamines. Polyamines can be considered supplementary defensive shielding molecules, important to protect the brain from the development of epilepsy and mental illnesses that are caused by different types of neurons. In this contest, the modulation of polyamine metabolism may be a novel important target for the prevention and therapeutic treatment of these diseases that have a high impact on the costs of public health and considerably affect quality of life. Contents

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“…Presently the self-organization and dynamics of this matrix are not understood beyond neuroanatomical descriptions. Altered densities of serotonergic (serotonin-releasing) fibers have been associated with many mental disorders and conditions, including Autism Spectrum Disorder (Azmitia et al, 2011 ), Major Depressive Disorder (Numasawa et al, 2017 ), epilepsy (Maia et al, 2019 ), and exposure to 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) (Adori et al, 2011 ). Predictive computational models can significantly advance this research and support its biomedical applications.…”

Section: Introductionmentioning

confidence: 99%

Serotonergic Axons as Fractional Brownian Motion Paths: Insights Into the Self-Organization of Regional Densities

Janušonis

Detering

Metzler

et al. 2020

Front. Comput. Neurosci.

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All vertebrate brains contain a dense matrix of thin fibers that release serotonin (5-hydroxytryptamine), a neurotransmitter that modulates a wide range of neural, glial, and vascular processes. Perturbations in the density of this matrix have been associated with a number of mental disorders, including autism and depression, but its self-organization and plasticity remain poorly understood. We introduce a model based on reflected Fractional Brownian Motion (FBM), a rigorously defined stochastic process, and show that it recapitulates some key features of regional serotonergic fiber densities. Specifically, we use supercomputing simulations to model fibers as FBM-paths in two-dimensional brain-like domains and demonstrate that the resultant steady state distributions approximate the fiber distributions in physical brain sections immunostained for the serotonin transporter (a marker for serotonergic axons in the adult brain). We suggest that this framework can support predictive descriptions and manipulations of the serotonergic matrix and that it can be further extended to incorporate the detailed physical properties of the fibers and their environment.

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Altered serotonin innervation in the rat epileptic brain

Cited by 20 publications

References 81 publications

Comprehensive topographical map of the serotonergic fibers in the male mouse brain

Comprehensive topographical map of the serotonergic fibers in the male mouse brain

Polyamines: The possible missing link between mental disorders and epilepsy (Review)

Serotonergic Axons as Fractional Brownian Motion Paths: Insights Into the Self-Organization of Regional Densities

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