Melatonin facilitates extinction, but not acquisition or expression, of conditional cued fear in rats

Huang, Fang; Yang, Zehua; Liu, Xiaoyan; Li, Chang-Qi

doi:10.1186/1471-2202-15-86

Cited by 22 publications

(11 citation statements)

References 58 publications

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“…Though we cannot rule out the possibility of very low expression below detection limits in astrocytes, our findings are consistent with data obtained by proteomic analysis of different cell types in the mouse brain 90 . Many other proteins like Serine racemase, Eps8, and HRD1 are known to be expressed only in neurons 91 – 93 . During development of the nervous system, neurogenesis precedes gliogenesis 94 .…”

Section: Discussionmentioning

confidence: 99%

Expression of a novel brain specific isoform of C3G is regulated during development

Sriram

Chintala

Parthasaradhi

et al. 2020

Sci Rep

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Mice lacking C3G (RapGEF1), a ubiquitously expressed protein essential for neuronal differentiation, show multiple defects in brain development. Function of C3G in neurogenesis is poorly defined. Here, we identify brain specific expression of a novel C3G isoform in mice and humans. This isoform has an insert in the Crk-binding region, generating a polypeptide of 175 kDa, unlike the previously known 140 kDa form expressed in all other tissues. In the adult mouse brain, C3G expression is seen in neurons, but was not detectable in GFAP-positive cells. C3G levels were high in the CA3 region of hippocampus and in mitral cells of olfactory bulb. Neural progenitor cells positive for Doublecortin and Nestin, show expression of C3G. During development, C3G is expressed in precursor cells prior to their differentiation into mature neurons or astrocytes. The 175 kDa as well as 140 kDa forms are seen in embryonic mouse brain, while only the 175 kDa variant is seen in post-natal brain. Human cerebral organoids generated from induced pluripotent stem cells predominantly expressed the 140 kDa polypeptides, and the 175 kDa isoform appeared upon maturation. This study describes developmental regulation and neuronal expression of a brain specific isoform of C3G, a molecule essential for normal development of the mammalian brain.

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Section: Discussionmentioning

confidence: 99%

Expression of a novel brain specific isoform of C3G is regulated during development

Sriram

Chintala

Parthasaradhi

et al. 2020

Sci Rep

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“…The roles in extinction of other 5-HT receptors or other components of the 5-HT system, such as melatonin (( Huang et al, 2014 ) have not been extensively explored. For example, recent work indicating that the 5-HT 7 receptor regulates emotional memories ( Eriksson et al, 2012 ), has not been followed up with studies on extinction.…”

Section: Pharmacologically Enhancing Extinctionmentioning

confidence: 99%

Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders

Singewald

Schmuckermair

Whittle

et al. 2015

Pharmacology & Therapeutics

355

271

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Pathological fear and anxiety are highly debilitating and, despite considerable advances in psychotherapy and pharmacotherapy they remain insufficiently treated in many patients with PTSD, phobias, panic and other anxiety disorders. Increasing preclinical and clinical evidence indicates that pharmacological treatments including cognitive enhancers, when given as adjuncts to psychotherapeutic approaches [cognitive behavioral therapy including extinction-based exposure therapy] enhance treatment efficacy, while using anxiolytics such as benzodiazepines as adjuncts can undermine long-term treatment success. The purpose of this review is to outline the literature showing how pharmacological interventions targeting neurotransmitter systems including serotonin, dopamine, noradrenaline, histamine, glutamate, GABA, cannabinoids, neuropeptides (oxytocin, neuropeptides Y and S, opioids) and other targets (neurotrophins BDNF and FGF2, glucocorticoids, L-type-calcium channels, epigenetic modifications) as well as their downstream signaling pathways, can augment fear extinction and strengthen extinction memory persistently in preclinical models. Particularly promising approaches are discussed in regard to their effects on specific aspects of fear extinction namely, acquisition, consolidation and retrieval, including long-term protection from return of fear (relapse) phenomena like spontaneous recovery, reinstatement and renewal of fear. We also highlight the promising translational value of the preclinial research and the clinical potential of targeting certain neurochemical systems with, for example d-cycloserine, yohimbine, cortisol, and L-DOPA. The current body of research reveals important new insights into the neurobiology and neurochemistry of fear extinction and holds significant promise for pharmacologically-augmented psychotherapy as an improved approach to treat trauma and anxiety-related disorders in a more efficient and persistent way promoting enhanced symptom remission and recovery.

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“…Melatonergic action has been shown to resemble sleep effects and prevent and/or reverse stress‐, SD‐ and aging‐related cognitive impairment and memory deterioration , as well as facilitate conditional cued fear extinction , without leading to next‐day cognitive impairment, as seen with other hypnotics . Reports suggest that interventions aimed at restoring normal hippocampal function, disrupting dysfunctional aversive memories and enhancing extinction of conditional cued fear may serve future treatment strategies for PTSD .…”

Section: Melatonergic Effects On Ptsd‐specific Pathophysiological Stamentioning

confidence: 99%

Potential pleiotropic beneficial effects of adjuvant melatonergic treatment in posttraumatic stress disorder

Agorastos

Linthorst

2016

Journal of Pineal Research

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Loss of circadian rhythmicity fundamentally affects the neuroendocrine, immune, and autonomic system, similar to chronic stress and may play a central role in the development of stress-related disorders. Recent articles have focused on the role of sleep and circadian disruption in the pathophysiology of posttraumatic stress disorder (PTSD), suggesting that chronodisruption plays a causal role in PTSD development. Direct and indirect human and animal PTSD research suggests circadian system-linked neuroendocrine, immune, metabolic and autonomic dysregulation, linking circadian misalignment to PTSD pathophysiology. Recent experimental findings also support a specific role of the fundamental synchronizing pineal hormone melatonin in mechanisms of sleep, cognition and memory, metabolism, pain, neuroimmunomodulation, stress endocrinology and physiology, circadian gene expression, oxidative stress and epigenetics, all processes affected in PTSD. In the current paper, we review available literature underpinning a potentially beneficiary role of an add-on melatonergic treatment in PTSD pathophysiology and PTSD-related symptoms. The literature is presented as a narrative review, providing an overview on the most important and clinically relevant publications. We conclude that adjuvant melatonergic treatment could provide a potentially promising treatment strategy in the management of PTSD and especially PTSD-related syndromes and comorbidities. Rigorous preclinical and clinical studies are needed to validate this hypothesis.

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Melatonin facilitates extinction, but not acquisition or expression, of conditional cued fear in rats

Cited by 22 publications

References 58 publications

Expression of a novel brain specific isoform of C3G is regulated during development

Expression of a novel brain specific isoform of C3G is regulated during development

Pharmacology of cognitive enhancers for exposure-based therapy of fear, anxiety and trauma-related disorders

Potential pleiotropic beneficial effects of adjuvant melatonergic treatment in posttraumatic stress disorder

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