Biology Reference
In-Depth Information
1. INTRODUCTION
Adult mammalian central nervous system (CNS) neurons do not
regenerate their axons after injury or in degenerative disease, as covered
elsewhere in this volume. Although progress had been made in deciphering
mechanisms of axon growth, regenerative failure remains amajor clinical prob-
lem (see Volume 106 Chapter 7). Serotonin (5-hydroxytryptamine, 5-HT)
was shown to regulate neurite growth of invertebrates through mammalian
CNS neurons. 5-HT regulates multiple biological processes, including neu-
rological, behavioral, endocrine, cardiovascular, gastrointestinal, urological,
and immunological (
Berger, Gray, & Roth, 2009; O'Connell et al.,
2006
). Classically, 5-HT operates as a transsynaptic messenger, although
5-HT also acts extrasynaptically (
De-Miguel & Trueta, 2005
), by
diffusion through tissues (
Vaney, 1986
), and through the circulation
(
Brenner et al., 2007; Maurer-Spurej, 2005
), and plays neuromodulatory
(
Dieudonn´ &Dumou in,2000
) and developmental (
Gaspar, Cases, &
Maroteaux, 2003; Lauder, Wallace, & Krebs, 1981; Sodhi & Sanders-
Bush, 2004
) roles. Within the CNS, 5-HT can regulate differentiation of
neural progenitors (
Lauder, Wallace, Krebs, Petrusz, & McCarthy, 1982
),
alter brain development (
Janusonis, Gluncic, & Rakic, 2004
), hone
formation of neuronal circuitry (
Daubert & Condron, 2010
), promote
neuronal survival (
Dooley, Pappas, & Parnavelas, 1997; Liu & Lauder,
1991
), stimulate astrocytes to secrete trophic factors like S100 (
Whitaker-
Azmitia, Murphy, & Azmitia, 1990
), modulate axon guidance (
Bonnin,
Torii, Wang, Rakic, & Levitt, 2007
), and act as a neuromodulator of
synapses and circuits (
Monckton & McCormick, 2002
). Here, we review
the role of 5-HT as a modulator of neurite growth (
Kater & Lipton,
1995; Lipton & Kater, 1989
).
2. 5-HT AFFECTS NEURITE GROWTH
2.1. Invertebrates and lower vertebrates
Studies in the
Helisoma
snail in ganglia neurons were the first to reveal that
5-HT plays a role in neurite growth. Application of 5-HT to Helisoma neu-
rons inhibits growth cone motility and growth rate of elongating neurites.
The effect was mediated locally, as focal application of 5-HT to the soma or
neurite did not affect the growth cone, whereas focal application of 5-HT to
the growth cone caused filopodial and lamellipodial retraction and a decrease
in the surface area of the growth cone. A small subpopulation of
Helisoma
