Neuroactive steroid pregnenolone sulphate inhibits long-term potentiation via activation of α2-adrenoreceptors at excitatory synapses in rat medial prefrontal cortex

Wang, Zemin; Qi, Yingjie; Wu, Pei‐Ying; Zhu, Yongping; Dong, Yan-Lian; Cheng, Zhengxiang; Zhu, Yanhua; Dong, Yi; Ma, Lan; Zheng, Ping

doi:10.1017/s1461145707008334

Cited by 11 publications

(7 citation statements)

References 52 publications

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“…Therefore, we first examined whether adenylyl cyclase (AC) and PKA were involved in the observed β 1 -adrenergic-dependent inward current. Extracellular application of the AC inhibitor MDL 12330A (20 μM, Wang et al, 2008 ; Zhang et al, 2009 ; Simons et al, 2012 ; Socodato et al, 2017 ) did not affect the amplitude of the dobutamine-dependent inward current. The dobutamine-dependent inward current amplitudes without and in the presence of the inhibitor in the bath were -32.11 ± 4.5 pA (n = 7) and -31.6 ± 2.5 pA (n = 9), respectively ( p = 0.9172, unpaired t-test, Figures 8Aa,b ).…”

Section: Resultsmentioning

confidence: 86%

Noradrenaline Modulates the Membrane Potential and Holding Current of Medial Prefrontal Cortex Pyramidal Neurons via β1-Adrenergic Receptors and HCN Channels

Grzelka

Kurowski

Gawlak

et al. 2017

Front. Cell. Neurosci.

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The medial prefrontal cortex (mPFC) receives dense noradrenergic projections from the locus coeruleus. Adrenergic innervation of mPFC pyramidal neurons plays an essential role in both physiology (control of memory formation, attention, working memory, and cognitive behavior) and pathophysiology (attention deficit hyperactivity disorder, posttraumatic stress disorder, cognitive deterioration after traumatic brain injury, behavioral changes related to addiction, Alzheimer’s disease and depression). The aim of this study was to elucidate the mechanism responsible for adrenergic receptor-mediated control of the resting membrane potential in layer V mPFC pyramidal neurons. The membrane potential or holding current of synaptically isolated layer V mPFC pyramidal neurons was recorded in perforated-patch and classical whole-cell configurations in slices from young rats. Application of noradrenaline (NA), a neurotransmitter with affinity for all types of adrenergic receptors, evoked depolarization or inward current in the tested neurons irrespective of whether the recordings were performed in the perforated-patch or classical whole-cell configuration. The effect of noradrenaline depended on β1- and not α1- or α2-adrenergic receptor stimulation. Activation of β1-adrenergic receptors led to an increase in inward Na+ current through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which carry a mixed Na+/K+ current. The protein kinase A- and C-, glycogen synthase kinase-3β- and tyrosine kinase-linked signaling pathways were not involved in the signal transduction between β1-adrenergic receptors and HCN channels. The transduction system operated in a membrane-delimited fashion and involved the βγ subunit of G-protein. Thus, noradrenaline controls the resting membrane potential and holding current in mPFC pyramidal neurons through β1-adrenergic receptors, which in turn activate HCN channels via a signaling pathway involving the βγ subunit.

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Section: Resultsmentioning

confidence: 86%

Noradrenaline Modulates the Membrane Potential and Holding Current of Medial Prefrontal Cortex Pyramidal Neurons via β1-Adrenergic Receptors and HCN Channels

Grzelka

Kurowski

Gawlak

et al. 2017

Front. Cell. Neurosci.

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“…Neurosteroids (PREGS) blocks LTP of excitatory synapses in rat medial prefrontal cortex (mPFC) via interaction with α 2 -adrenoreceptors secondary to enhancement of Gi proteins. After treatment of mPFC slices with the α 2 -adrenoreceptor inhibitor “yohimbine,” the blocking effect of PREGS on the induction of LTP was completely inhibited ( 72 ).…”

Section: Effect Of Nassmentioning

confidence: 99%

Neuroactive Steroids: Receptor Interactions and Responses

Tuem

Atey

2017

Front. Neurol.

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Neuroactive steroids (NASs) are naturally occurring steroids, which are synthesized centrally as de novo from cholesterol and are classified as pregnane, androstane, and sulfated neurosteroids (NSs). NASs modulate many processes via interacting with gamma-aminobutyric acid (GABA), N-methyl-d-aspartate, serotonin, voltage-gated calcium channels, voltage-dependent anion channels, α-adrenoreceptors, X-receptors of the liver, transient receptor potential channels, microtubule-associated protein 2, neurotrophin nerve growth factor, and σ1 receptors. Among these, NSs (especially allopregnanolone) have high potency and extensive GABA-A receptors and hence demonstrate anticonvulsant, anesthetic, central cytoprotectant, and baroreflex inhibitory effects. NSs are also involved in mood and learning via serotonin and anti-nociceptive activity via T-type voltage-gated Ca2+ channels. Moreover, they are modulators of mitochondrial function, synaptic plasticity, or regulators of apoptosis, which have a role in neuroprotective via voltage-dependent anion channels receptors. For proper functioning, NASs need to be in their normal level, whereas excess and deficiency may lead to abnormalities. When they are below the normal, NSs could have a part in development of depression, neuro-inflammation, multiple sclerosis, experimental autoimmune encephalitis, epilepsy, and schizophrenia. On the other hand, stress and attention deficit disorder could occur during excessive level. Overall, NASs are very important molecules with major neuropsychiatric activity.

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“…In accordance, blockade of these receptors prevents the induction of LTP (Kemp & Manahan‐Vaughan, 2008; Flores et al 2010). In contrast, the activation of adrenergic α1 and α2 receptors reduces LTP (Mondaca et al 2004; Takamatsu et al 2008; Wang et al 2008), and therefore counteracts the effects of β‐adrenergic receptors on plasticity. With regard to LTD, the effects of β‐adrenergic receptor activation are conflicting: Kemp & Manahan‐Vaughan (2008), as well as Lemon and colleagues (Lemon et al 2009) described an enhancement of LTD, whereas a diminution or prevention was found in other studies (Katsuki et al 1997; Lin et al 2008).…”

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confidence: 99%

The pharmacology of neuroplasticity induced by non‐invasive brain stimulation: building models for the clinical use of CNS active drugs

Nitsche

Müller‐Dahlhaus

Paulus

et al. 2012

The Journal of Physiology

171

119

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The term neuroplasticity encompasses structural and functional modifications of neuronal connectivity. Abnormal neuroplasticity is involved in various neuropsychiatric diseases, such as dystonia, epilepsy, migraine, Alzheimer's disease, fronto-temporal degeneration, schizophrenia, and post cerebral stroke. Drugs affecting neuroplasticity are increasingly used as therapeutics in these conditions. Neuroplasticity was first discovered and explored in animal experimentation. However, non-invasive brain stimulation (NIBS) has enabled researchers recently to induce and study similar processes in the intact human brain. Plasticity induced by NIBS can be modulated by pharmacological interventions, targeting ion channels, or neurotransmitters. Importantly, abnormalities of plasticity as studied by NIBS are directly related to clinical symptoms in neuropsychiatric diseases. Therefore, a core theme of this review is the hypothesis that NIBS-induced plasticity can explore and potentially predict the therapeutic efficacy of CNS-acting drugs in neuropsychiatric diseases. We will (a) review the basics of neuroplasticity, as explored in animal experimentation, and relate these to our knowledge about neuroplasticity induced in humans by NIBS techniques. We will then (b) discuss pharmacological modulation of plasticity in animals and humans. Finally, we will (c) review abnormalities of plasticity in neuropsychiatric diseases, and discuss how the combination of NIBS with pharmacological intervention may improve our understanding of the pathophysiology of abnormal plasticity in these diseases and their purposeful pharmacological treatment.Ulf Ziemann (far left) is clinical director of the Department of Neurology and Stroke, Hertie Institute for Clinical Brain Research, Eberhard-Karls University of Tübingen, Germany. His expertise is in clinical neurophysiology with focus on motor cortical excitability, plasticity, learning and neurorehabilitation. He has developed the field of pharmaco-TMS, which provides important knowledge on the physiology of TMS measures of excitability and the pharmacological regulation of plasticity in human motor cortex. Florian Müller-Dahlhaus (centre left) is resident at the Department of Neurology, Goethe-University Frankfurt, Germany. He has expertise in cellular electrophysiology and imaging as well as pharmaco-TMS. Research focuses on understanding mechanisms of neural plasticity involved in motor learning to enhance rehabilitation post stroke. Walter Paulus (centre right) is clinical director of the Department of Clinical Neurophysiology, University Medical Centre, Germany. He investigates motor cortex physiology by means of transcranial stimulation, further refined by co-application of CNS-active drugs. He was involved in the development of new stimulation methods for induction of neuroplasticity such as tDCS, tACS and tRNS. His clinical focus encompasses Parkinson's disease, restless legs syndrome, epilepsy and pain. Michael A. Nitsche (far right) is a consultant in the same department. His ...

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Neuroactive steroid pregnenolone sulphate inhibits long-term potentiation via activation of α2-adrenoreceptors at excitatory synapses in rat medial prefrontal cortex

Cited by 11 publications

References 52 publications

Noradrenaline Modulates the Membrane Potential and Holding Current of Medial Prefrontal Cortex Pyramidal Neurons via β1-Adrenergic Receptors and HCN Channels

Noradrenaline Modulates the Membrane Potential and Holding Current of Medial Prefrontal Cortex Pyramidal Neurons via β1-Adrenergic Receptors and HCN Channels

Neuroactive Steroids: Receptor Interactions and Responses

The pharmacology of neuroplasticity induced by non‐invasive brain stimulation: building models for the clinical use of CNS active drugs

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