Biology Reference
In-Depth Information
neurons was unaffected by 5-HT (
Haydon, McCobb, & Kater, 1984
). Fur-
thermore, despite such inhibitory effects on actively growing neurites,
5-HT elicited reinitiation of neurite elongation in a subpopulation of sta-
tionary neurites from embryonic but not adult
Helisoma
neurons. Under
no circumstances, however, did 5-HT increase the growth rate of neurites
that were already in an active growth state (
Goldberg, Mills, & Kater, 1991
).
Similarly, in
Lymnaea stagnalis
cerebral giant cells, 5-HT inhibited elongat-
ing neurites' growth and collapsed the growth cone—an effect that was blocked
by 5-HT receptor antagonist methysergide (
Koertetal.,2001
). In goldfish
retinal explants, 5-HT decreased neurite outgrowth (
Lima,Matu ,&
Urbina, 1994
). Also in goldfish, intraocular injection of 5-HT after optic
nerve crush
in vivo
resulted in decreased neurite outgrowth after the retina
was explanted and neurite outgrowth measured in culture (
Lima, Urbina,
Matus, & Drujan, 1996
). Together, these data suggested that 5-HT may
play an inhibitory role in axon growth or regeneration of mature CNS
neurons, and that identifying and decreasing the activity of 5-HT
receptors subtypes mediating this effect could promote regeneration.
2.2. Mammals
How does 5-HT affect neurite growth of mammalian neurons? 5-HT
inhibited neurite growth of embryonic rat serotonergic neurons dissected from
raphe nuclei (
Liu&Lauder, 1991
). 5-HT also inhibited total neurite length and
branching, but not primary (two longest neurites) neurites' length, in cultured
embryonic rat cortical neurons (
Sikich, Hickok, &Todd, 1990
). The selective
serotonin reuptake inhibitor fluoxetine suppressed neurite growth of cultured
rat primary cortical neurons (
Xu et al., 2010
). From these data, 5-HTappears to
have an exclusively inhibitory role. However, 5-HT increased total neurite
length and branching in cultured embryonic (E15.5) mouse thalamic neurons,
starting at 0.1
m
M and peaking at 30
m
M(
Persico, Di Pino, & Levitt, 2006
). In
organotypic postnatal day 7 (P7) rats anterior lobe cerebellar slice cultures,
5-HT increased or decreased Purkinje cell dendrite growth after 4 days
in vitro
(DIV), depending on concentration, 2 or 20
m
M, respectively; whereas in pos-
terior lobe cerebellar slice cultures, 5-HT increased purkinje cell dendrites
growth even at 200
m
M(
Kondoh, Shiga, & Okado, 2004
). In PC12 cells,
5-HT stimulated neurite outgrowth at concentrations ranging from 5 to
0.5 mM (
Severin & Kondratyev, 1988
) and acted synergistically with nerve
growth factor to increase neurite outgrowth (
Homma, Kitamura, Ogawa, &
Oka, 2006; Severin & Kondratyev, 1988
). Similarly, 5-HT increased
neurites outgrowth from Neuro 2A cell-line cells but did not promote
existing neurite growth unless
the cells were transfected with Htr1A
