Dopamine Regulates Adult Neurogenesis in the Ventricular-Subventricular Zone via Dopamine D3 Angiotensin Type 2 Receptor Interactions

Abstract

Adult neurogenesis is a dynamic and highly regulated process, and different studies suggest that dopamine modulates ventricular-subventricular zone (V-SVZ) neurogenesis. However, the specific role of dopamine and the mechanisms/factors underlying its effects on physiological and pathological conditions such as Parkinson's disease (PD) are not fully understood. Recent studies have described counter-regulatory interactions between renin-angiotensin system (RAS) and dopamine in peripheral tissues and in the nigrostriatal system. We have previously demonstrated that angiotensin receptors regulate proliferation and generation of neuroblasts in the rodent V-SVZ. However, possible interactions between dopamine receptors and RAS in the V-SVZ and their role in alterations of neurogenesis in animal models of PD have not been investigated. In V-SVZ cultures, activation of dopamine receptors induced changes in the expression of angiotensin receptors. Moreover, dopamine, via D2-like receptors and particularly D3 receptors, increased generation of neurospheres derived from the V-SVZ and this effect was mediated by angiotensin type-2 (AT2) receptors. In rats, we observed a marked reduction in proliferation and generation of neuroblasts in the V-SVZ of dopamine-depleted animals, and inhibition of AT1 receptors or activation of AT2 receptors restored proliferation and generation of neuroblasts to control levels. Moreover, intrastriatal mesencephalic grafts partially restored proliferation and generation of neuroblasts observed in the V-SVZ of dopamine-depleted rats. Our data revealed that dopamine and angiotensin receptor interactions play a major role in the regulation of V-SVZ and suggest potential beneficial effects of RAS modulators on the regulation of adult V-SVZ neurogenesis.

Effect of Haloperidol and Olanzapine on Hippocampal Cells’ Proliferation in Animal Model of Schizophrenia

“…We showed that HAL was able to suppress the inhibitory effect of MK-801 on DCX . Previous studies have shown that dopamine positively regulates cell proliferation, and proliferation decreases after dopamine depletion can be reversed by dopamine stimulation in vivo [ 40 ]. Dopamine is able to modulate NMDA receptor activity, and D2 receptors have been shown to reduce NMDA receptor activity and neuronal calcium influx [ 41 ].…”

Dopaminergic neurons are not a major Sonic hedgehog ligand source for striatal cholinergic or PV interneurons

“…We have recently reported that the deletion of the Shh receptor Smoothened (SMO) in Glial fibrillary acidic protein (GFAP) positive NSCs at the perinatal stage leads to premature aging-related decline of adult neurogenesis ( Wang et al., 2022 ). DA neuron projections have been described at the SVZ region where the adult neural stem cells reside and have been suggested to regulate SVZ neurogenesis through the release of factors such as dopamine ( Garcia-Garrote et al., 2021 ; Hoglinger et al., 2004 ). Therefore, we decided to examine whether DA neuron projections from the midbrain to the STR/SVZ region could be a critical source of SHH ligand for maintaining Shh signaling in NSCs.…”

“…We and others have reported that abolishing Shh signaling in the mGFAPcre mouse line results in decreased adult neurogenesis in both the SVZ and SGZ, and our recent study shows that Shh KO further accelerates the age-related decline in adult neurogenesis and contributes to increased anxiety in mGFAP-smo cKO mice ( Wang et al., 2022 ). As SN DA neuron projections have been previously reported to regulate SVZ NSCs at least partially through the release of dopamine ( Garcia-Garrote et al., 2021 ; Hoglinger et al., 2004 ), we examined whether midbrain DA neuron projections could potentially provide SHH ligand to the SVZ NSCs in order to maintain their homeostasis. However, our data show that at 3 months of age, there is no difference in either the population of proliferating cells (Ki67+) or newly differentiated neuroblasts (DCX+) in the SVZ, suggesting midbrain DA neuron projections are not a critical source for maintaining Shh signaling in SVZ NSCs.…”

An integrated microfluidic chip for studying the effects of neurotransmitters on neurospheroids

“…[4][5][6][7] The neurotransmitters dopamine and serotonin have been found to have positive effects on neurogenesis and proliferation within the CNS. [8][9][10][11][12][13][14] For instance, some research groups reported that the neurotransmitter dopamine plays a role in regulating endogenous neurogenesis in the adult mammalian brain such as in the ventricular-subventricular zone (V-SVZ). 9,15 The counter-regulatory interactions between the renin-angiotensin system and dopamine in peripheral tissues and in the nigrostriatal system have been reported.…”

“…[8][9][10][11][12][13][14] For instance, some research groups reported that the neurotransmitter dopamine plays a role in regulating endogenous neurogenesis in the adult mammalian brain such as in the ventricular-subventricular zone (V-SVZ). 9,15 The counter-regulatory interactions between the renin-angiotensin system and dopamine in peripheral tissues and in the nigrostriatal system have been reported. However, the specific role of dopamine and the mechanisms underlying its effects on physiological and pathological conditions such as neurodegenerative diseases remain unclear.…”