Reduced programmed cell death in brains of serotonin transporter knockout mice.
Serotonin (5-HT) is known to reduce apoptosis and in rodent models of brain ischemia. Modulation of programmed cell death during neural development was assessed in early postnatal brains of serotonin transporter (5-HTT) knockout mice, characterized by elevated extracellular 5-HT levels. The number of apoptotic cells visualized at postnatal day-1 (P1) by ISEL+ or TUNEL staining was significantly reduced in the striatum, thalamus/hypothalamus, cerebral cortex and hippocampus of 5-HTT knockout mice, compared to wild type and heterozygote mice, with differences displaying an increasing fronto-caudal gradient and regional specificity. These findings underscore 5-HT roles in the regulation of programmed cell death during brain development, and spur interest into pharmacological interventions aimed at relieving pathological apoptosis by potentiating serotoninergic neurotransmission.
Persico
Antonio M
AM
Laboratory of Molecular Psychiatry and Neurogenetics, University Campus Bio-Medico, Italy. a.persico@unicampus.it
Baldi
Alfonso
A
Dell'Acqua
Maria Luisa
ML
Moessner
Rainald
R
Murphy
Dennis L
DL
Lesch
Klaus-Peter
KP
Keller
Flavio
F
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D006579:Heterozygote; D008562:Membrane Glycoproteins / Q000502:physiology*; D026901:Membrane Transport Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D012016:Reference Values; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D012701:Serotonin