Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis

Azmitia, Efrain C.

doi:10.1016/s0361-9230(01)00614-1

Cited by 459 publications

(340 citation statements)

References 111 publications

Supporting

Mentioning

311

Contrasting

Unclassified

Order By: Relevance

“…6I). Importantly, the concentration of 5-HT detected (approximately 12 nM) is well within the concentration range (10 −9 M) required for the activation of 5-HT 1A receptors (35,41). The involvement of 5-HT 1A receptors is confirmed by the direct modulation induced by 8-OH-DPAT in the presence of the 5-HT 7 receptor antagonist SB269970 (Fig.…”

Section: Discussionsupporting

confidence: 59%

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

Cotel

Exley

Cragg

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

133

141

View full text Add to dashboard Cite

Motor fatigue induced by physical activity is an everyday experience characterized by a decreased capacity to generate motor force. Factors in both muscles and the central nervous system are involved. The central component of fatigue modulates the ability of motoneurons to activate muscle adequately independently of the muscle physiology. Indirect evidence indicates that central fatigue is caused by serotonin (5-HT), but the cellular mechanisms are unknown. In a slice preparation from the spinal cord of the adult turtle, we found that prolonged stimulation of the raphespinal pathway-as during motor exercise-activated 5-HT 1A receptors that decreased motoneuronal excitability. Electrophysiological tests combined with pharmacology showed that focal activation of 5-HT 1A receptors at the axon initial segment (AIS), but not on other motoneuronal compartments, inhibited the action potential initiation by modulating a Na + current. Immunohistochemical staining against 5-HT revealed a high-density innervation of 5-HT terminals on the somatodendritic membrane and a complete absence on the AIS. This observation raised the hypothesis that a 5-HT spillover activates receptors at this latter compartment. We tested it by measuring the level of extracellular 5-HT with cyclic voltammetry and found that prolonged stimulations of the raphe-spinal pathway increased the level of 5-HT to a concentration sufficient to activate 5-HT 1A receptors. Together our results demonstrate that prolonged release of 5-HT during motor activity spills over from its release sites to the AIS of motoneurons. Here, activated 5-HT 1A receptors inhibit firing and, thereby, muscle contraction. Hence, this is a cellular mechanism for central fatigue.movement | spike genesis | input-output gain | movement control P rolonged physical activity leads to motor fatigue (1, 2). The force produced by muscles decreases in part because of the lack of glycogen (3) in the muscle and/or failures at the neuromuscular junctions (4). In addition to this well-described muscle fatigue, motor fatigue also involves an element originating in the CNS (5-8). This "central fatigue" is characterized by a decreased ability to contract the muscle fibers adequately during a motor activity and is observed independently of the muscle fatigue (6). It is often studied during maximal voluntary contractions (5, 6, 9). Nevertheless, it is also present during weak physical contraction (1,2,8,(10)(11)(12). Central fatigue secures rotation of motor units (13) and prevents hyperactivity of muscles (6). Elements of central fatigue involve the cortex (6), and the spinal cord at the level of motoneurons (MNs) (5).The cellular mechanisms responsible for a decrease of the activity of MNs remain unknown. However, evidence suggests that central fatigue correlates with increased levels of serotonin (5-HT) in the CNS. Human subjects that perform an intense motor task are faster exhausted after intake of a 5-HT 1A receptor agonist (14) or a selective serotonin reuptake inhibitor (15). In animals, inject...

show abstract

Section: Discussionsupporting

confidence: 59%

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

Cotel

Exley

Cragg

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

133

141

View full text Add to dashboard Cite

show abstract

“…6,7 Studies have linked exposure to antidepressants in utero to persistent pulmonary hypertension of the newborn and pulmonary diseases. 8,9 Exposure to antidepressants in utero may also increase the possibility of fetal growth restriction, 10 a risk factor for the development of asthma.…”

Section: What This Study Addsmentioning

confidence: 99%

Antidepressant Use During Pregnancy and Asthma in the Offspring

et al. 2015

View full text Add to dashboard Cite

show abstract

“…For example, serotonin induces growth cone collapse and neurite retraction in neurons of chick dorsal root ganglion (Igarashi et al, 1995). The several serotonin receptors, including 5-HT 1A , 5-HT 2A , and 5-HT 2B , have been proposed to be involved in the modulation of such neurotrophic events produced by 5-HT in mammals (Yan et al, 1997;Fiorica-Howells et al, 2000;Azmitia, 2001).…”

Section: -Ht 7 R/g12 Signaling and Neuronal Morphologymentioning

confidence: 99%

5-HT₇Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology

Kvachnina¹,

Liu²,

Dityatev³

et al. 2005

J. Neurosci.

180

220

View full text Add to dashboard Cite

The neurotransmitter serotonin (5-HT) plays an important role in the regulation of multiple events in the CNS. We demonstrated recently a coupling between the 5-HT 4 receptor and the heterotrimeric G13-protein resulting in RhoA-dependent neurite retraction and cell rounding (Ponimaskin et al., 2002). In the present study, we identified G12 as an additional G-protein that can be activated by another member of serotonin receptors, the 5-HT 7 receptor. Expression of 5-HT 7 receptor induced constitutive and agonist-dependent activation of a serum response element-mediated gene transcription through G12-mediated activation of small GTPases. In NIH3T3 cells, activation of the 5-HT 7 receptor induced filopodia formation via a Cdc42-mediated pathway correlating with RhoA-dependent cell rounding. In mouse hippocampal neurons, activation of the endogenous 5-HT 7 receptors significantly increased neurite length, whereas stimulation of 5-HT 4 receptors led to a decrease in the length and number of neurites. These data demonstrate distinct roles for 5-HT 7 R/G12 and 5-HT 4 R/G13 signaling pathways in neurite outgrowth and retraction, suggesting that serotonin plays a prominent role in regulating the neuronal cytoarchitecture in addition to its classical role as neurotransmitter.

show abstract

Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis

Cited by 459 publications

References 111 publications

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

Antidepressant Use During Pregnancy and Asthma in the Offspring

5-HT₇Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology

Contact Info

Product

Resources

About

Modern views on an ancient chemical: serotonin effects on cell proliferation, maturation, and apoptosis

Cited by 459 publications

References 111 publications

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

Serotonin spillover onto the axon initial segment of motoneurons induces central fatigue by inhibiting action potential initiation

Antidepressant Use During Pregnancy and Asthma in the Offspring

5-HT7Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology

Contact Info

Product

Resources

About

5-HT₇Receptor Is Coupled to Gα Subunits of Heterotrimeric G12-Protein to Regulate Gene Transcription and Neuronal Morphology