Pregnenolone sulfate increases glutamate release at neonatal climbing fiber-to-Purkinje cell synapses

Zamudio-Bulcock, Paula A.; Valenzuela, C. Fernando

doi:10.1016/j.neuroscience.2010.11.063

Cited by 24 publications

(29 citation statements)

References 57 publications

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“…Progesterone, on the other hand, has been shown to have inhibitory effects, reducing the number of dendritic spines and excitatory synapses Increased glutamate levels in the MPFC in patients with PPD AM McEwen et al (Woolley and McEwen, 1993). Animal studies have also shown both that NASs can modulate glutamatergic neurons (Zamudio-Bulcock and Valenzuela, 2011) and that Glu impacts the production of NASs (Remage-Healey et al, 2008). Considering the known interactions between female hormones, NASs and glutamatergic activity, it is therefore possible that the fluctuations of female hormones and NASs in the postpartum contribute to the increased MPFC Glu fluctuations observed in PPD women.…”

Section: Discussionmentioning

confidence: 99%

Increased Glutamate Levels in the Medial Prefrontal Cortex in Patients with Postpartum Depression

McEwen

Burgess

Hanstock

et al. 2012

Neuropsychopharmacol

103

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The medial prefrontal cortex (MPFC) is a key brain area in depressive symptomatology; specifically, glutamate (Glu) has been reported to play a significant role in major depression (MD) in this area. MPFC Glu levels are sensitive to ovarian hormone fluctuations and pregnancy and the postpartum period are associated with the most substantial physiological alterations of female hormones. It is therefore logical to measure MPFC Glu levels in women with postpartum depression (PPD). Using in vivo magnetic resonance spectroscopy (MRS) at a field strength of 3 T, we acquired single-voxel spectra from the MPFC of 12 women with PPD and 12 healthy controls (HCs) matched for postpartum scan timing. Water-referenced MPFC Glu levels were measured using a MRS technique that allowed us to be specific for Glu with very little glutamine contamination. The concentrations of other water-quantified brain metabolites such as glycerophosphorylcholine plus phosphorylcholine, N-acetylaspartate (NAA), and creatine plus phosphocreatine were measured in the same MR spectra. MPFC Glu levels were higher in women with PPD (7.21±1.20) compared to matched HCs (6.04±1.21). There were no differences between groups for other brain metabolites measured. These findings suggest an association between Glu dysregulation in the MPFC and PPD. Whether the pathophysiology of PPD differs from the pathophysiology of MD remains to be determined. Further investigations are needed to determine the chronological associations between the occurrence of symptoms of PPD and the onset of changes in MPFC Glu levels.

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Section: Discussionmentioning

confidence: 99%

Increased Glutamate Levels in the Medial Prefrontal Cortex in Patients with Postpartum Depression

McEwen

Burgess

Hanstock

et al. 2012

Neuropsychopharmacol

103

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“…It is activated by intracellular adenosine diphosphoribose (ADPR), hydrogen peroxide, heat, and reactive oxygen species (ROS; Nilius et al, ; Wu et al, ). Abundantly expressed in neonatal cerebellar Purkinje cells, the steroid‐sensitive TRPM3 channel is required for pregnenolone sulfate‐induced glutamate release (Zamudio‐Bulcock and Valenzuela, ; Zamudio‐Bulcock et al, ). TRPM4 and TRPM5 channels are the only two members of the TRP superfamily that are Ca 2+ ‐impermeable monovalent channels (Nilius et al, ).…”

Section: Expression and Functions Of Trp Channels In The Brainmentioning

confidence: 99%

Brain transient receptor potential channels and stroke

Zhang

Liao

2014

J of Neuroscience Research

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Transient receptor potential (TRP) channels have been increasingly implicated in the pathological mechanisms of CNS disorders. TRP expression has been detected in neurons, astrocytes, oligodendrocytes, microglia, and ependymal cells as well as in the cerebral vascular endothelium and smooth muscle. In stroke, TRPC3/4/6, TRPM2/4/7, and TRPV1/3/4 channels have been found to participate in ischemia-induced cell death, whereas other TRP channels, in particular those expressed in nonneuronal cells, have been less well studied. This review summarizes the current knowledge on the expression and functions of the TRP channels in various cell types in the brain and our current understanding of TRP channels in stroke pathophysiology. In an aging society, the occurrence of stroke is expected to increase steadily, and there is an urgent requirement to improve the current stroke management strategy. Therefore, elucidating the roles of TRP channels in stroke could shed light on the development of novel therapeutic strategies and ultimately improve stroke outcome.

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“…In the developing cerebellum, PregS strongly and reversibly enhances glutamate release onto Purkinje cells (PCs) of neonatal rats, an effect that is independent of several PregS‐sensitive targets; namely, NMDA, glycine, α7 nicotinic acetylcholine, and σ1 receptors, as well as voltage‐gated Ca 2+ channels (Zamudio‐Bulcock and Valenzuela 2011). PregS increases glutamate release by enhancing Ca 2+ entrance into pre‐synaptic terminals via a target that is sensitive to La 3+ , a non‐selective agent that modulates a number of TRP channel subtypes and is known to block TRPM3 (Zholos 2010; Zamudio‐Bulcock and Valenzuela 2011). Based on this finding, we hypothesized that TRPM3 channels are expressed at developing glutamatergic synapses on PCs and that they mediate the PregS‐induced enhancement of glutamatergic transmission.…”

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confidence: 99%

Activation of steroid‐sensitive TRPM3 channels potentiates glutamatergic transmission at cerebellar Purkinje neurons from developing rats

Zamudio-Bulcock

Everett

Harteneck

et al. 2011

Journal of Neurochemistry

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The functional implications of transient receptor potential melastatin 3 (TRPM3) activation, the most recently described member of the melastatin subfamily of cation permeable TRP channels, have begun to be elucidated in recent years. The discovery of TRPM3 activation by the steroid pregnenolone sulfate (PregS) has shed new light on the physiological role of this channel. For example, TRPM3 activation enhances insulin secretion from β pancreatic cells, induces contraction of vascular smooth muscle, and is also involved in the detection of noxious heat. Although TRPM3 expression has been detected in several regions of the developing and mature brain, little is known about the roles of TRPM3 in brain physiology. Here, we demonstrate the abundant expression of TRPM3 steroid-sensitive channels in the developing cerebellar cortex. We also show that TRPM3-like channels are expressed at glutamatergic synapses in neonatal Purkinje cells (PCs). We recently showed that PregS potentiates spontaneous glutamate release onto neonatal PCs during a period of active glutamatergic synapse formation; we now show that this effect of PregS is mediated by TRPM3-like channels. Mefenamic acid, a recently discovered TRPM3 antagonist, blocked the effect of PregS on glutamate release. The PregS effect on glutamate release was mimicked by other TRPM3 agonists (nifedipine and epipregnanolone sulfate) but not by a TRMP3-inactive steroid (progesterone). Our findings identify TRPM3 channels as novel modulators of glutamatergic transmission in the developing brain.

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Pregnenolone sulfate increases glutamate release at neonatal climbing fiber-to-Purkinje cell synapses

Cited by 24 publications

References 57 publications

Increased Glutamate Levels in the Medial Prefrontal Cortex in Patients with Postpartum Depression

Increased Glutamate Levels in the Medial Prefrontal Cortex in Patients with Postpartum Depression

Brain transient receptor potential channels and stroke

Activation of steroid‐sensitive TRPM3 channels potentiates glutamatergic transmission at cerebellar Purkinje neurons from developing rats

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