TY - JOUR
T1 - Adult neurogenesis in serotonin transporter deficient mice
AU - Schmitt, A.
AU - Benninghoff, J.
AU - Moessner, R.
AU - Rizzi, M.
AU - Paizanis, E.
AU - Doenitz, C.
AU - Gross, S.
AU - Hermann, M.
AU - Gritti, A.
AU - Lanfumey, L.
AU - Fritzen, S.
AU - Reif, A.
AU - Hamon, M.
AU - Murphy, D. L.
AU - Vescovi, A.
AU - Lesch, K. P.
PY - 2007/9
Y1 - 2007/9
N2 - Serotonin (5-HT) is a regulator of morphogenetic activities during early brain development and neurogenesis, including cell proliferation, migration, differentiation, and synaptogenesis. The 5-HT transporter (5-HTT, SLC6A4) mediates high-affinity reuptake of 5-HT into presynaptic terminals and thereby fine-tunes serotonergic neurotransmission. Inactivation of the 5-HTT gene in mice reduces 5-HT clearance resulting in persistently increased concentrations of synaptic 5-HT. In the present study, we investigated the effects of elevated 5-HT levels on adult neurogenesis in the hippocampus of 5-HTT deficient mice, including stem cell proliferation, survival, and differentiation. Using an in vivo approach, we showed an increase in proliferative capacity of hippocampal adult neural stem cells in aged 5-HTT knockout mice (∼14.5 months) compared to wildtype controls. In contrast, in vivo and additional in vitro analyses of younger adult 5-HTT knockout mice (∼7 weeks and ∼3.0 months) did not reveal significant changes in proliferation of neural stem cells or survival of newborn cells. We showed that the cellular fate of newly generated cells in 5-HTT knockout mice is not different with respect to the total number and percentage of neurons or glial cells from wildtype controls. Our findings indicate that elevated synaptic 5-HT concentration throughout early development and later life of 5-HTT deficient mice does not induce adult neurogenesis in adult mice, but that elevated 5-HT levels in aged mice influence stem cell proliferation.
AB - Serotonin (5-HT) is a regulator of morphogenetic activities during early brain development and neurogenesis, including cell proliferation, migration, differentiation, and synaptogenesis. The 5-HT transporter (5-HTT, SLC6A4) mediates high-affinity reuptake of 5-HT into presynaptic terminals and thereby fine-tunes serotonergic neurotransmission. Inactivation of the 5-HTT gene in mice reduces 5-HT clearance resulting in persistently increased concentrations of synaptic 5-HT. In the present study, we investigated the effects of elevated 5-HT levels on adult neurogenesis in the hippocampus of 5-HTT deficient mice, including stem cell proliferation, survival, and differentiation. Using an in vivo approach, we showed an increase in proliferative capacity of hippocampal adult neural stem cells in aged 5-HTT knockout mice (∼14.5 months) compared to wildtype controls. In contrast, in vivo and additional in vitro analyses of younger adult 5-HTT knockout mice (∼7 weeks and ∼3.0 months) did not reveal significant changes in proliferation of neural stem cells or survival of newborn cells. We showed that the cellular fate of newly generated cells in 5-HTT knockout mice is not different with respect to the total number and percentage of neurons or glial cells from wildtype controls. Our findings indicate that elevated synaptic 5-HT concentration throughout early development and later life of 5-HTT deficient mice does not induce adult neurogenesis in adult mice, but that elevated 5-HT levels in aged mice influence stem cell proliferation.
KW - Adult neurogenesis
KW - Aging
KW - Anxiety
KW - Depression
KW - Knockout
KW - Serotonin transporter
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U2 - 10.1007/s00702-007-0724-6
DO - 10.1007/s00702-007-0724-6
M3 - Article
C2 - 17510734
AN - SCOPUS:34548179797
SN - 0300-9564
VL - 114
SP - 1107
EP - 1119
JO - Journal of Neural Transmission
JF - Journal of Neural Transmission
IS - 9
ER -