Biology Reference
In-Depth Information
neurons cultures, selective Htr3 agonist m-CPBG promoted neurite exten-
sion and branching (
Persico et al., 2006
). However, in cultured embryonic
(E16) rat cortical neurons, Htr3 receptor agonist SR57227 decreased axon
and dendrite length of non-GABAergic neurons, and the effect was reversed
by incubation with Htr3 antagonist ondansetron, although the same agonist
did not affect neurite growth of GABAergic neurons (
Hayashi et al.,
2010
). No gross brain abnormalities were reported in Htr3A knockout mice
(
Walstab, Rappold, & Niesler, 2010; Zeitz et al., 2002
), but an increase in
apical dendrite complexity of maturing postnatal mouse cortical neurons
(
Chameau et al., 2009; Smit-Rigter, Wadman, & van Hooft, 2011; van der
Velden, van Hooft, & Chameau, 2012
) was demonstrated. As the
in vitro
evidence for Htr3A's role in neurite growth is primarily pharmacological,
Htr3A knockdown and overexpression should be investigated, and tested in
axon regeneration model, as above. Furthermore, because the effect appears
to be opposite depending on the cell type, Htr3A needs to be tested under
the same experimental conditions in different neuronal types and ages.
3.5. Htr4/5/7
These three receptors have received less attention in studies of neurite
growth.
In vitro
, in 1-2 days postnatal dissociated mouse hippocampal cul-
tures, Htr4-selective agonist BIMU8 decreased the number of neurites per
cell, and this effect was blocked by a selective Htr4 antagonist GR113808
(
Kvachnina et al., 2005
). In the same study and in similar
in vitro
culture con-
ditions, 100 nM Htr7-specific agonist 5-CT increased neurite length,
although the number of neurites was not affected, and Htr7 antagonist
SB269970 blocked this effect. Overexpression of Htr7 in these hippocampal
cultures increased neurite length when incubated with 1
m
M 5-HT,
although in control transfected cultures, 1
m
M 5-HT reduced neurite length
(
Kvachnina et al., 2005
). This effect appears to be restricted to early devel-
opmental stages, as 5-CT did not significantly affect neuronal morphology in
the adult mouse hippocampal cultures (
Kobe et al., 2012
).
In vivo
, Htr7
expression transiently increased during early postnatal stages in mouse hip-
pocampus and potentiates formation of dendritic spines and promotes syn-
aptogenesis as shown in hippocampal explants (
Kobe et al., 2012
). However,
knockouts of Htr4 (
Compan et al., 2004
), Htr5A (
Grailhe et al., 1999
), or
Htr7 (
Guscott et al., 2005; Hedlund, 2009; Hedlund et al., 2003; Witkin,
Baez, Yu, Barton, & Shannon, 2007
)
in mice result
in no overt
abnormities in axonal growth or brain development.
