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The G Protein-Coupled Serotonin 1A Receptor Augments Protein Kinase Cε-Mediated Neurogenesis in Neonatal Mouse Hippocampus—PKCε-Mediated Signaling in the Early Hippocampus
by
Purkayastha, Sudarshana
, Schroder, Ryan
, Chanthrakumar, Pranavan
, Diallo, Souleymane
, Tantry, Subramanyam J.
, Flory, Michael J.
, Samaddar, Sreyashi
, Banerjee, Probal
in
8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology
/ Animals
/ Animals, Newborn
/ Anxiety
/ Apoptosis - drug effects
/ Autism
/ Brain research
/ Bromodeoxyuridine - pharmacology
/ Dentate Gyrus - drug effects
/ Dentate Gyrus - metabolism
/ Dentate Gyrus - physiology
/ Female
/ Hippocampus - drug effects
/ Hippocampus - metabolism
/ Hippocampus - physiology
/ Kinases
/ Male
/ Mental depression
/ Mice
/ Mice, Inbred C57BL
/ Neurogenesis
/ Neurogenesis - drug effects
/ Neurogenesis - physiology
/ Neurons
/ Neurons - drug effects
/ Neurons - metabolism
/ Neurons - physiology
/ Protein Kinase C-epsilon - metabolism
/ Proteins
/ Receptor, Serotonin, 5-HT1A - metabolism
/ Receptors, G-Protein-Coupled - metabolism
/ Serotonin - metabolism
/ Serotonin Receptor Agonists - pharmacology
/ Signal Transduction - drug effects
/ Signal Transduction - physiology
2022
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The G Protein-Coupled Serotonin 1A Receptor Augments Protein Kinase Cε-Mediated Neurogenesis in Neonatal Mouse Hippocampus—PKCε-Mediated Signaling in the Early Hippocampus
by
Purkayastha, Sudarshana
, Schroder, Ryan
, Chanthrakumar, Pranavan
, Diallo, Souleymane
, Tantry, Subramanyam J.
, Flory, Michael J.
, Samaddar, Sreyashi
, Banerjee, Probal
in
8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology
/ Animals
/ Animals, Newborn
/ Anxiety
/ Apoptosis - drug effects
/ Autism
/ Brain research
/ Bromodeoxyuridine - pharmacology
/ Dentate Gyrus - drug effects
/ Dentate Gyrus - metabolism
/ Dentate Gyrus - physiology
/ Female
/ Hippocampus - drug effects
/ Hippocampus - metabolism
/ Hippocampus - physiology
/ Kinases
/ Male
/ Mental depression
/ Mice
/ Mice, Inbred C57BL
/ Neurogenesis
/ Neurogenesis - drug effects
/ Neurogenesis - physiology
/ Neurons
/ Neurons - drug effects
/ Neurons - metabolism
/ Neurons - physiology
/ Protein Kinase C-epsilon - metabolism
/ Proteins
/ Receptor, Serotonin, 5-HT1A - metabolism
/ Receptors, G-Protein-Coupled - metabolism
/ Serotonin - metabolism
/ Serotonin Receptor Agonists - pharmacology
/ Signal Transduction - drug effects
/ Signal Transduction - physiology
2022
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The G Protein-Coupled Serotonin 1A Receptor Augments Protein Kinase Cε-Mediated Neurogenesis in Neonatal Mouse Hippocampus—PKCε-Mediated Signaling in the Early Hippocampus
by
Purkayastha, Sudarshana
, Schroder, Ryan
, Chanthrakumar, Pranavan
, Diallo, Souleymane
, Tantry, Subramanyam J.
, Flory, Michael J.
, Samaddar, Sreyashi
, Banerjee, Probal
in
8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology
/ Animals
/ Animals, Newborn
/ Anxiety
/ Apoptosis - drug effects
/ Autism
/ Brain research
/ Bromodeoxyuridine - pharmacology
/ Dentate Gyrus - drug effects
/ Dentate Gyrus - metabolism
/ Dentate Gyrus - physiology
/ Female
/ Hippocampus - drug effects
/ Hippocampus - metabolism
/ Hippocampus - physiology
/ Kinases
/ Male
/ Mental depression
/ Mice
/ Mice, Inbred C57BL
/ Neurogenesis
/ Neurogenesis - drug effects
/ Neurogenesis - physiology
/ Neurons
/ Neurons - drug effects
/ Neurons - metabolism
/ Neurons - physiology
/ Protein Kinase C-epsilon - metabolism
/ Proteins
/ Receptor, Serotonin, 5-HT1A - metabolism
/ Receptors, G-Protein-Coupled - metabolism
/ Serotonin - metabolism
/ Serotonin Receptor Agonists - pharmacology
/ Signal Transduction - drug effects
/ Signal Transduction - physiology
2022
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The G Protein-Coupled Serotonin 1A Receptor Augments Protein Kinase Cε-Mediated Neurogenesis in Neonatal Mouse Hippocampus—PKCε-Mediated Signaling in the Early Hippocampus
Journal Article
The G Protein-Coupled Serotonin 1A Receptor Augments Protein Kinase Cε-Mediated Neurogenesis in Neonatal Mouse Hippocampus—PKCε-Mediated Signaling in the Early Hippocampus
2022
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Overview
The neurotransmitter serotonin (5-HT) plays an important role in mood disorders. It has been demonstrated that 5-HT signaling through 5-HT1A receptors (5-HT1A-R) is crucial for early postnatal hippocampal development and later-life behavior. Although this suggests that 5-HT1A-R signaling regulates early brain development, the mechanistic underpinnings of this process have remained unclear. Here we show that stimulation of the 5-HT1A-R at postnatal day 6 (P6) by intrahippocampal infusion of the agonist 8-OH-DPAT (D) causes signaling through protein kinase Cε (PKCε) and extracellular receptor activated kinase ½ (ERK1/2) to boost neuroblast proliferation in the dentate gyrus (DG), as displayed by an increase in bromodeoxy-uridine (BrdU), doublecortin (DCX) double-positive cells. This boost in neuroproliferation was eliminated in mice treated with D in the presence of a 5-HT1A-R antagonist (WAY100635), a selective PKCε inhibitor, or an ERK1/2-kinase (MEK) inhibitor (U0126). It is believed that hippocampal neuro-progenitors undergoing neonatal proliferation subsequently become postmitotic and enter the synaptogenesis phase. Double-staining with antibodies against bromodeoxyuridine (BrdU) and neuronal nuclear protein (NeuN) confirmed that 5-HT1A-R → PKCε → ERK1/2-mediated boosted neuroproliferation at P6 also leads to an increase in BrdU-labeled granular neurons at P36. This 5-HT1A-R-mediated increase in mature neurons was unlikely due to suppressed apoptosis, because terminal deoxynucleotidyl transferase dUTP nick-end labeling analysis showed no difference in DNA terminal labeling between vehicle and 8-OH-DPAT-infused mice. Therefore, 5-HT1A-R signaling through PKCε may play an important role in micro-neurogenesis in the DG at P6, following which many of these new-born neuroprogenitors develop into mature neurons.
Publisher
MDPI AG,MDPI
Subject
8-Hydroxy-2-(di-n-propylamino)tetralin - pharmacology
/ Animals
/ Anxiety
/ Autism
/ Bromodeoxyuridine - pharmacology
/ Dentate Gyrus - drug effects
/ Female
/ Kinases
/ Male
/ Mice
/ Neurons
/ Protein Kinase C-epsilon - metabolism
/ Proteins
/ Receptor, Serotonin, 5-HT1A - metabolism
/ Receptors, G-Protein-Coupled - metabolism
/ Serotonin Receptor Agonists - pharmacology
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