Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of γ-aminobutyric acid A receptors （...Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of γ-aminobutyric acid A receptors （GABAARs）, which play a vital role in pain modulation in the lateral thalamus, a main gate where somatosensory information enters the cerebral cortex. Using high-perfor mance liquid chromatography/tandem mass spectrometry, we found increased levels of neurosteroids （pregnenolone, progesterone, deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone） in the chronic stage of neuropathic pain （28 days after spared nerve injury） in rats.The expression of the translocator protein TSPO, the upstream steroidogenesis rate-limiting enzyme, increased at the same time. In vivo stereotaxic microinjection of neurosteroids or the TSPO activator AC-5216 into the lateral thalamus （AP -3.0 mm, ML 4-3.0 mm, DV 6.0 mm） alleviated the mechanical allodynia in neuropathic pain, while the TSPO inhibitor PK 11195 exacerbated it. The analgesic effects of AC-5216 and neurosteroids were sig- nificantly attenuated by the GABAAR antagonist bicuculline. These results suggested that elevated neurosteroids in the lateral thalamus play a protective role in the chronic stage of neuropathic pain.展开更多
The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functio...The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.展开更多
Steroids and ecdysteroids have been shown to exhibit a range of biological effects,including anti-inflammatory,anticancer,and neuroprotective.This systematic review aims to highlight the evidence-based neuroprotective...Steroids and ecdysteroids have been shown to exhibit a range of biological effects,including anti-inflammatory,anticancer,and neuroprotective.This systematic review aims to highlight the evidence-based neuroprotective and antioxidant effects of steroids and ecdysteroids in SH-SY5Y neuroblastoma cells.A comprehensive literature search was conducted on May 11,2023,without publication source restrictions,using various electronic databases,including PubMed,Web of Science(WoS),Scopus,and Cumulative Index toNursing and Allied Health Literature.Of 103articles,only20 studies were included for investigating the neuroprotective effects of steroids and ecdysteroids in SH-SY5Y cells exposed to oxidative stress or neurotoxic agents.The risk of bias and quality assessment of the included studies were evaluated in accordance with the Nature Publication Quality Improvement Project specific criteria.The selected studies reported the antioxidant effects of the tested compounds on SH-SY5Y cells and demonstrated their ability to scavenge free radicals and prevent lipid peroxidation.These findings suggest that neurosteroids have potential therapeutic applications for the prevention and treatment of neurodegenerative diseases characterized by oxidative stress and neuronal damage.Some studies have investigated the molecular mechanisms underlying the neuroprotective and antioxidant effects of steroids and ecdysteroids in SH-SY5Y cells.These mechanisms include the activation of antioxidant enzymes,such as superoxide dismutase and glutathione peroxidase,and the modulation of various signaling pathways,including the phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways.This review provides evidence that the tested compounds have remarkable neuroprotective and antioxidant effects in human neuroblastoma SH-SY5Y cells.展开更多
The thought of exploring a possible relationship between the broad systems of steroid hormone physiology (specifically vitamin D and testosterone) and nocioception was prompted by an unexpectedly frequent personal cli...The thought of exploring a possible relationship between the broad systems of steroid hormone physiology (specifically vitamin D and testosterone) and nocioception was prompted by an unexpectedly frequent personal clinical observation. Patients with chronic pain syndromes or chronic musculoskeletal pain often have low serum levels of vitamin D and testos-terone. Mining for relevant information in Pub Med, Medline and Cochrane Systems Review, three concepts repeatedly emerge that provide a common context for understanding the mechanics of these diverse sys-tems—epigenetic, homeostasis and neuroplasticity. Viewing homeostasis within the framework of epigenetics allows reasoned speculation as to how various human systems interact to maintain integrity and function, while simultaneously responding in a plastic manner to external stimuli. Cell signaling supports normal function by regulating synaptic activity, but can also effect plastic change in the central and peripheral nervous system. This is most commonly achieved by post-translational remodeling of chromatin. There is thus persistent epigenetic change in protein synthesis with all the related downstream effects but without disruption of normal DNA se-quencing. In itself, this may be considered an example of genomic homeo-stasis. Epigenetic mechanisms in nociception and analgesia are active in the paleospinothalamic and neospinothalamic tracts at all levels. Physiologic response to a nociceptive insult, whether mechanical, inflammatory or ischemic, is provided by cell signaling that is significantly enhanced through epigenetic mechanisms at work in nociceptors, Gamma-Aminobutyric Acid (GABA) and glutamate receptors, voltage gated receptors, higher order neurons in the various dorsal horn laminae and proximal nociceptive pro-cessing centers in the brainstem and cortex. The mediators of these direct or epigenetic effects are various ligands also active in signaling, such as free radicals, substance P, a variety of cytokines, growth factors and G proteins, stress展开更多
基金supported by grants from the National Basic Research Development Program of China(2013CB531905,2014CB548200,and 2015CB554503)the National Natural Science Foundation of China(81230023,81221002,31200835,81571067,and 21305005)+1 种基金a Key Project of the Ministry of Education of China(109003)the ‘‘111’’ Project of the Ministry of Education of China(B07001)
文摘Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of γ-aminobutyric acid A receptors （GABAARs）, which play a vital role in pain modulation in the lateral thalamus, a main gate where somatosensory information enters the cerebral cortex. Using high-perfor mance liquid chromatography/tandem mass spectrometry, we found increased levels of neurosteroids （pregnenolone, progesterone, deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone） in the chronic stage of neuropathic pain （28 days after spared nerve injury） in rats.The expression of the translocator protein TSPO, the upstream steroidogenesis rate-limiting enzyme, increased at the same time. In vivo stereotaxic microinjection of neurosteroids or the TSPO activator AC-5216 into the lateral thalamus （AP -3.0 mm, ML 4-3.0 mm, DV 6.0 mm） alleviated the mechanical allodynia in neuropathic pain, while the TSPO inhibitor PK 11195 exacerbated it. The analgesic effects of AC-5216 and neurosteroids were sig- nificantly attenuated by the GABAAR antagonist bicuculline. These results suggested that elevated neurosteroids in the lateral thalamus play a protective role in the chronic stage of neuropathic pain.
基金funded by the Taylor Family Institute for Innovative Psychiatric Researchthe Bantly FoundationMH122379 from the National Institute of Mental Health (to YI)。
文摘The etiological factors contributing to depression and other neuropsychiatric disorders are largely undefined. Endoplasmic reticulum stress pathways and autophagy are well-defined mechanisms that play critical functions in recognizing and resolving cellular stress and are possible targets for the pathophysiology and treatment of psychiatric and neurologic illnesses. An increasing number of studies indicate the involvement of endoplasmic reticulum stress and autophagy in the control of neuroinflammation, a contributing factor to multiple neuropsychiatric illnesses. Initial inflammatory triggers induce endoplasmic reticulum stress, leading to neuroinflammatory responses. Subsequently, induction of autophagy by neurosteroids and other signaling pathways that converge on autophagy induction are thought to participate in resolving neuroinflammation. The aim of this review is to summarize our current understanding of the molecular mechanisms governing the induction of endoplasmic reticulum stress, autophagy, and neuroinflammation in the central nervous system. Studies focused on innate immune factors, including neurosteroids with anti-inflammatory roles will be reviewed. In the context of depression, animal models that led to our current understanding of molecular mechanisms underlying depression will be highlighted, including the roles of sigma 1 receptors and pharmacological agents that dampen endoplasmic reticulum stress and associated neuroinflammation.
基金Stipendium Hungaricum Scholarship founded by the Hungarian Government。
文摘Steroids and ecdysteroids have been shown to exhibit a range of biological effects,including anti-inflammatory,anticancer,and neuroprotective.This systematic review aims to highlight the evidence-based neuroprotective and antioxidant effects of steroids and ecdysteroids in SH-SY5Y neuroblastoma cells.A comprehensive literature search was conducted on May 11,2023,without publication source restrictions,using various electronic databases,including PubMed,Web of Science(WoS),Scopus,and Cumulative Index toNursing and Allied Health Literature.Of 103articles,only20 studies were included for investigating the neuroprotective effects of steroids and ecdysteroids in SH-SY5Y cells exposed to oxidative stress or neurotoxic agents.The risk of bias and quality assessment of the included studies were evaluated in accordance with the Nature Publication Quality Improvement Project specific criteria.The selected studies reported the antioxidant effects of the tested compounds on SH-SY5Y cells and demonstrated their ability to scavenge free radicals and prevent lipid peroxidation.These findings suggest that neurosteroids have potential therapeutic applications for the prevention and treatment of neurodegenerative diseases characterized by oxidative stress and neuronal damage.Some studies have investigated the molecular mechanisms underlying the neuroprotective and antioxidant effects of steroids and ecdysteroids in SH-SY5Y cells.These mechanisms include the activation of antioxidant enzymes,such as superoxide dismutase and glutathione peroxidase,and the modulation of various signaling pathways,including the phosphoinositide 3-kinase/protein kinase B and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways.This review provides evidence that the tested compounds have remarkable neuroprotective and antioxidant effects in human neuroblastoma SH-SY5Y cells.
文摘The thought of exploring a possible relationship between the broad systems of steroid hormone physiology (specifically vitamin D and testosterone) and nocioception was prompted by an unexpectedly frequent personal clinical observation. Patients with chronic pain syndromes or chronic musculoskeletal pain often have low serum levels of vitamin D and testos-terone. Mining for relevant information in Pub Med, Medline and Cochrane Systems Review, three concepts repeatedly emerge that provide a common context for understanding the mechanics of these diverse sys-tems—epigenetic, homeostasis and neuroplasticity. Viewing homeostasis within the framework of epigenetics allows reasoned speculation as to how various human systems interact to maintain integrity and function, while simultaneously responding in a plastic manner to external stimuli. Cell signaling supports normal function by regulating synaptic activity, but can also effect plastic change in the central and peripheral nervous system. This is most commonly achieved by post-translational remodeling of chromatin. There is thus persistent epigenetic change in protein synthesis with all the related downstream effects but without disruption of normal DNA se-quencing. In itself, this may be considered an example of genomic homeo-stasis. Epigenetic mechanisms in nociception and analgesia are active in the paleospinothalamic and neospinothalamic tracts at all levels. Physiologic response to a nociceptive insult, whether mechanical, inflammatory or ischemic, is provided by cell signaling that is significantly enhanced through epigenetic mechanisms at work in nociceptors, Gamma-Aminobutyric Acid (GABA) and glutamate receptors, voltage gated receptors, higher order neurons in the various dorsal horn laminae and proximal nociceptive pro-cessing centers in the brainstem and cortex. The mediators of these direct or epigenetic effects are various ligands also active in signaling, such as free radicals, substance P, a variety of cytokines, growth factors and G proteins, stress
