Serotonin in Space: Understanding Single Fibers

Janušonis, Skirmantas

doi:10.1021/acschemneuro.6b00417

Cited by 9 publications

(7 citation statements)

References 6 publications

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“…If fibers are not static and continue to grow in the adult brain, it raises a natural question: What processes allow achieving a steady equilibrium of densities? We have previously suggested that in the healthy brain serotonergic fibers may be routinely interrupted and that these interruptions may be associated with microglia . By using super-resolution microscopy (STED), we now have obtained evidence consistent with this hypothesis (Figure C).…”

supporting

confidence: 75%

“…We have previously suggested that in the healthy brain serotonergic fibers may be routinely interrupted and that these interruptions may be associated with microglia. 2 By using super-resolution microscopy (STED), we now have obtained evidence consistent with this hypothesis (Figure 2C). We note that this finding should not be generalized without more extensive studies.…”

Section: Acs Chemical Neurosciencesupporting

confidence: 65%

“…These models will be important for fundamental neuroscience and may also lead to new insights in biomedical research. For example, an increase in fiber density may be caused by more individual fibers invading the tissue volume or by a stronger tortuosity of individual fibers, with no change in the fiber number. , Also, it is not known whether individual fibers walk through large areas, freely mixing with other fibers, or whether they establish local territories that other fibers cannot invade. This level of description will play a progressively important role in the identification and characterization of mental disorders.…”

mentioning

confidence: 99%

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Serotonergic Axons as 3D-Walks

Janušonis

Mays

Hingorani

2019

ACS Chem. Neurosci.

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supporting

confidence: 75%

Section: Acs Chemical Neurosciencesupporting

confidence: 65%

mentioning

confidence: 99%

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Serotonergic Axons as 3D-Walks

Janušonis

Mays

Hingorani

2019

ACS Chem. Neurosci.

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“…In this study, 5-HT-immunoreactive fibers are most concentrated in the area within the NTS defined as the dorsomedial region (Phifer and Berthoud, 1998; Pool et al, 2007; Zheng et al, 1999). In serotonergic fibers, 5-HT is concentrated in specialized varicosities with variable dimensions (Bjarkam et al, 2003; Janušonis, 2017; Ruda et al, 1982). In the current study, a 15-min exposure to FPL64176 resulted in a moderate enhancement of 5-HT immunoreactivity within the dorsomedial subdivision of the NTS, marked by numerous varicosities of varying sizes, suggesting subdivision-specific response to administration of FPL64176.…”

Section: Discussionmentioning

confidence: 99%

Intracellular emetic signaling evoked by the L-type Ca2+ channel agonist FPL64176 in the least shrew (Cryptotis parva)

Zhong

Chebolu

Darmani

2018

European Journal of Pharmacology

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Ca2+ plays a major role in maintaining cellular homeostasis and regulates processes including apoptotic cell death and side-effects of cancer chemotherapy including vomiting. Currently we explored the emetic mechanisms of FPL64176, an L-type Ca2+ channel (LTCC) agonist with maximal emetogenic effect at its 10 mg/kg dose. FPL64176 evoked c-Fos immunoreactivity in shrew brainstem sections containing the vomit-associated nuclei, nucleus tractus solitarius (NTS) and dorsal motor nucleus of the vagus. FPL64176 also increased phosphorylation of proteins ERK1/2, PKCα/βII and Akt in the brainstem. Moreover, their corresponding inhibitors (PD98059, GF 109203X and LY294002, respectively) reduced FPL64176-evoked vomiting. A 30 min subcutaneous (s.c.) pretreatment with the LTCC antagonist nifedipine (10 mg/kg) abolished FPL64176-elicited vomiting, c-Fos expression, and emetic effector phosphorylation. Ryanodine receptors (RyRs) and inositol trisphosphate receptors (IP3Rs) mediate intracellular Ca2+ release from the sarcoplasmic/endoplasmic reticulum. The RyR antagonist dantrolene (i.p.), or a combination of low doses of nifedipine and dantrolene, but not the IP3R antagonist 2-APB, significantly attenuated FPL64176-induced vomiting. The serotonin type 3 receptor (5-HT3R) antagonist palonosetron (s.c.), the neurokinin 1 receptor (NK1R) antagonist netupitant (i.p.) or a combination of non-effective doses of netupitant and palonosetron showed antiemetic potential against FPL64176-evoked vomiting. Serotonin (5-HT) and substance P immunostaining revealed FPL64176-induced emesis was accompanied by an increase in 5-HT but not SP-immunoreactivity in the dorsomedial subdivision of the NTS. These findings demonstrate that Ca2+ mobilization through LTCCs and RyRs, and subsequent emetic effector phosphorylation and 5-HT release play important roles in FPL64176-induced emesis which can be prevented by 5-HT3R and NK1R antagonists.

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“…It has been estimated that there are around 6 × 10 6 varicosities/mm 3 in the rat cortex. In addition, each cortical neuron may receive around 200 varicosities ( 94 , 95 ). However, there is evidence of some non-5-HT producing neurons that transiently express 5-HTT during development in the thalamus identified by 5-HT uptake and in situ hybridization for 5-HTT RNA ( 96 ).…”

Section: Visualizing Serotonin Axonsmentioning

confidence: 99%

Rewiring of the Serotonin System in Major Depression

Vahid-Ansari

Albert

2021

Front. Psychiatry

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Serotonin is a key neurotransmitter that is implicated in a wide variety of behavioral and cognitive phenotypes. Originating in the raphe nuclei, 5-HT neurons project widely to innervate many brain regions implicated in the functions. During the development of the brain, as serotonin axons project and innervate brain regions, there is evidence that 5-HT plays key roles in wiring the developing brain, both by modulating 5-HT innervation and by influencing synaptic organization within corticolimbic structures. These actions are mediated by 14 different 5-HT receptors, with region- and cell-specific patterns of expression. More recently, the role of the 5-HT system in synaptic re-organization during adulthood has been suggested. The 5-HT neurons have the unusual capacity to regrow and reinnervate brain regions following insults such as brain injury, chronic stress, or altered development that result in disconnection of the 5-HT system and often cause depression, anxiety, and cognitive impairment. Chronic treatment with antidepressants that amplify 5-HT action, such as selective serotonin reuptake inhibitors (SSRIs), appears to accelerate the rewiring of the 5-HT system by mechanisms that may be critical to the behavioral and cognitive improvements induced in these models. In this review, we survey the possible 5-HT receptor mechanisms that could mediate 5-HT rewiring and assess the evidence that 5-HT-mediated brain rewiring is impacting recovery from mental illness. By amplifying 5-HT-induced rewiring processes using SSRIs and selective 5-HT agonists, more rapid and effective treatments for injury-induced mental illness or cognitive impairment may be achieved.

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Serotonin in Space: Understanding Single Fibers

Cited by 9 publications

References 6 publications

Serotonergic Axons as 3D-Walks

Serotonergic Axons as 3D-Walks

Intracellular emetic signaling evoked by the L-type Ca2+ channel agonist FPL64176 in the least shrew (Cryptotis parva)

Rewiring of the Serotonin System in Major Depression

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