Adult hippocampal neurogenesis (ahNG) is a peculiar form of neural plasticity involved in crucial... more Adult hippocampal neurogenesis (ahNG) is a peculiar form of neural plasticity involved in crucial brain functions including cognition, mood and stress response. Adult hippocampal neural progenitor cells (ahNPC) differentiation is modulated positively or negatively by several factors. Understanding the mechanisms regulating ahNG will shed light on its role in brain physiopathology. Astrocytes, one of the major component of the neurogenic niche, might regulate ahNPC fate specification. Little is known about the identity of astrocytes-secreted proteins and the subcellular mechanisms mediating their modulatory effect. Interestingly ahNG is deregulated in neuropsychiatric disorders such as major depression. The specific involvement of serotonin (5-HT) receptors family in mediating antidepressants (AD) effect add more complication into serotonin role in depression and is still not extensively described. Several studies documented a role of NF-?B signaling in ahNPC response to proneurogeni...
In the brain, glucose homeostasis of extracellular fluid is crucial to the point that systems spe... more In the brain, glucose homeostasis of extracellular fluid is crucial to the point that systems specifically dedicated to glucose sensing are found in areas involved in energy regulation and feeding behavior. Olfaction is a major sensory modality regulating food consumption. Nutritional status in turn modulates olfactory detection. Recently it has been proposed that some olfactory bulb (OB) neurons respond to glucose similarly to hypothalamic neurons. However, the precise molecular cues governing glucose sensing in the OB are largely unknown. To decrypt these molecular mechanisms, we first used immunostaining to demonstrate a strong expression of two neuronal markers of glucose-sensitivity, insulin-dependent glucose transporter type 4 (GLUT4), and sodium glucose co-transporter type 1 (SGLT1) in specific OB layers. We showed that expression and mapping of GLUT4 but not SGLT1 were feeding state-dependent. In order to investigate the impact of metabolic status on the delivery of blood-bo...
Several antidepressants increase adult hippocampal Neurogenesis (ahNG) in rodents, primates and, ... more Several antidepressants increase adult hippocampal Neurogenesis (ahNG) in rodents, primates and, potentially, in humans. This effect may at least partially account for their therapeutic activity. The availability of antidepressants whose mechanism of action involves different neurotransmitter receptors represents an opportunity for increasing our knowledge on their distinctive peculiarities and for dissecting the contribution of receptor subtypes in ahNG modulation. The aim of this study was to evaluate, in vitro, the effects of the antidepressant trazodone (TZD) on ahNG by using primary cultures of adult hippocampal Neural Progenitor Cells (ahNPC) and human iPSC-derived NPC. We demonstrated that TZD enhances neuronal differentiation of murine as well as human NPC. TZD is a multimodal antidepressant which binds with high affinity 5-HT2a, α1, 5-HT1a and with lower affinity 5-HT2c and 5-HTT. We demonstrated that TZD proneurogenic effects were mediated by 5-HT2a antagonism both in muri...
In previous work, we demonstrated that NF-κB p50 acts as crucial regulator of adult hippocampal n... more In previous work, we demonstrated that NF-κB p50 acts as crucial regulator of adult hippocampal neural progenitor cells (ahNPC). Indeed, NF-κB p50 knockout (KO) mice are characterized by remarkably reduced hippocampal neurogenesis. As a follow up to that work, herein we show that when cultured in vitro, ahNPC from wild type (WT) and p50KO mice are not significantly different in their neurogenic potential. This observation prompted us to investigate cell-autonomous and noncell-autonomous consequences of p50 absence on neuronal fate specification of ahNPC. In particular, we focused our attention on astrocytes, known to provide soluble proneurogenic signals, and investigated the influence of WT and p50KO astrocyte conditioned media (ACM) on WT and p50KO ahNPC differentiation. Interestingly, while WT ACM promoted both neuronal and astroglial differentiations, p50KO ACM only supported astroglial differentiation of WT ahNPC. By using a LC-MS/MS approach, we identified some proteins, which...
Adult hippocampal neurogenesis (ahNG) is a peculiar form of neural plasticity involved in crucial... more Adult hippocampal neurogenesis (ahNG) is a peculiar form of neural plasticity involved in crucial brain functions including cognition, mood and stress response. Adult hippocampal neural progenitor cells (ahNPC) differentiation is modulated positively or negatively by several factors. Understanding the mechanisms regulating ahNG will shed light on its role in brain physiopathology. Astrocytes, one of the major component of the neurogenic niche, might regulate ahNPC fate specification. Little is known about the identity of astrocytes-secreted proteins and the subcellular mechanisms mediating their modulatory effect. Interestingly ahNG is deregulated in neuropsychiatric disorders such as major depression. The specific involvement of serotonin (5-HT) receptors family in mediating antidepressants (AD) effect add more complication into serotonin role in depression and is still not extensively described. Several studies documented a role of NF-?B signaling in ahNPC response to proneurogeni...
In the brain, glucose homeostasis of extracellular fluid is crucial to the point that systems spe... more In the brain, glucose homeostasis of extracellular fluid is crucial to the point that systems specifically dedicated to glucose sensing are found in areas involved in energy regulation and feeding behavior. Olfaction is a major sensory modality regulating food consumption. Nutritional status in turn modulates olfactory detection. Recently it has been proposed that some olfactory bulb (OB) neurons respond to glucose similarly to hypothalamic neurons. However, the precise molecular cues governing glucose sensing in the OB are largely unknown. To decrypt these molecular mechanisms, we first used immunostaining to demonstrate a strong expression of two neuronal markers of glucose-sensitivity, insulin-dependent glucose transporter type 4 (GLUT4), and sodium glucose co-transporter type 1 (SGLT1) in specific OB layers. We showed that expression and mapping of GLUT4 but not SGLT1 were feeding state-dependent. In order to investigate the impact of metabolic status on the delivery of blood-bo...
Several antidepressants increase adult hippocampal Neurogenesis (ahNG) in rodents, primates and, ... more Several antidepressants increase adult hippocampal Neurogenesis (ahNG) in rodents, primates and, potentially, in humans. This effect may at least partially account for their therapeutic activity. The availability of antidepressants whose mechanism of action involves different neurotransmitter receptors represents an opportunity for increasing our knowledge on their distinctive peculiarities and for dissecting the contribution of receptor subtypes in ahNG modulation. The aim of this study was to evaluate, in vitro, the effects of the antidepressant trazodone (TZD) on ahNG by using primary cultures of adult hippocampal Neural Progenitor Cells (ahNPC) and human iPSC-derived NPC. We demonstrated that TZD enhances neuronal differentiation of murine as well as human NPC. TZD is a multimodal antidepressant which binds with high affinity 5-HT2a, α1, 5-HT1a and with lower affinity 5-HT2c and 5-HTT. We demonstrated that TZD proneurogenic effects were mediated by 5-HT2a antagonism both in muri...
In previous work, we demonstrated that NF-κB p50 acts as crucial regulator of adult hippocampal n... more In previous work, we demonstrated that NF-κB p50 acts as crucial regulator of adult hippocampal neural progenitor cells (ahNPC). Indeed, NF-κB p50 knockout (KO) mice are characterized by remarkably reduced hippocampal neurogenesis. As a follow up to that work, herein we show that when cultured in vitro, ahNPC from wild type (WT) and p50KO mice are not significantly different in their neurogenic potential. This observation prompted us to investigate cell-autonomous and noncell-autonomous consequences of p50 absence on neuronal fate specification of ahNPC. In particular, we focused our attention on astrocytes, known to provide soluble proneurogenic signals, and investigated the influence of WT and p50KO astrocyte conditioned media (ACM) on WT and p50KO ahNPC differentiation. Interestingly, while WT ACM promoted both neuronal and astroglial differentiations, p50KO ACM only supported astroglial differentiation of WT ahNPC. By using a LC-MS/MS approach, we identified some proteins, which...
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Papers by Rita Salem