About
85
Publications
11,059
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
1,840
Citations
Introduction
Dr. Fang-Chia Chang, Ph.D., a Taiwanese neuroscience and sleep medicine expert, is a Distinguished Professor at NTU’s School of Veterinary Medicine. He directs the Neurobiology & Cognitive Science Center, chaired the Taiwan International Graduate Program, and earned multiple awards for teaching, mentoring, and research innovation.
Skills and Expertise
Current institution
Additional affiliations
August 2014 - present
August 2011 - present
Publications
Publications (85)
Artificial light exposure, particularly from blue-rich sources, has raised concerns about its impact on sleep and circadian rhythms. While blue light’s effects are well-documented, the comparative impact of longer wavelengths, such as orange light (590–635 nm), remains underexplored. This study investigated the effects of 8 h blue (470–490 nm) and...
Background: Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective in ameliorating the negative and cognitive symptoms of schizophrenia. The aims of the present stu...
Hypofunction of the glutamate system in the brain is one of the pathophysiological hypotheses for schizophrenia. Accumulating animal and clinical studies show that sarcosine (N-methylglycine), a glycine transporter-1 inhibitor, is effective for ameliorating the negative and cognitive symptoms of schizophrenia. The aims of the present study were to...
Transcranial direct current stimulation (tDCS) is acknowledged for its non-invasive modulation of neuronal activity in psychiatric disorders. However, its application in insomnia research yields varied outcomes depending on different tDCS types and patient conditions. Our primary objective is to elucidate its efficiency and uncover the underlying m...
Transcranial direct current stimulation (tDCS) is acknowledged for its non-invasive modulation of neuronal activity in psychiatric disorders. However, its application in insomnia research yields varied outcomes depending on different tDCS types and patient conditions. Our primary objective is to elucidate its efficiency and uncover the underlying m...
Chronic post-traumatic stress disorder (PTSD) exhibits psychological abnormalities during fear memory processing in rodent models. To simulate long-term impaired fear extinction in PTSD patients, we constructed a seven-day model with multiple prolonged stress (MPS) by modifying manipulation repetitions, intensity, and unpredictability of stressors....
Introduction
Posttraumatic stress disorder (PTSD) is a psychiatric disorder developed in individuals who expose to traumatic events. These patients may experience symptoms, such as recurrent unwanted memory of the traumatic event, avoidance of reminders of the trauma, increased arousal, and cognitive difficulty. The hypocretinergic system originate...
An acute stressor can cause sleep disruptions. Electroencephalography (EEG) is one of the major tools to measure sleep. In rats, sleep stages are classified as rapid-eye movement (REM) sleep and non-rapid-eye movement (NREM) sleep, by different characteristics of EEGs. Sleep alterations after exposure to an acute stress are regularly determined by...
Sleep disturbances have been the hallmark of the recent coronavirus disease 2019 pandemic. Studies have shown that once sleep is disrupted, it can lead to psychological and physical health issues which can, in turn, disrupt circadian rhythm and induce further sleep disruption. As consumers are trying to establish healthy routines, nutritional and p...
Hypocretin (hcrt) is a stress-reacting neuropeptide mediating arousal and energy homeostasis. An inescapable footshock stimulation (IFS) could initiate the hcrt release from the lateral hypothalamus (LHA) and suppresses rapid eye movement (REM) sleep in rodents. However, the effects of the IFS-induced hcrts on REM-off nuclei, the locus coeruleus (L...
Background
Sleep disruption is a major public health issue and may increase the risk of mortality by ten-folds if an individual is sleeping less than 6 h per night. Sleep has changed dramatically during to the COVID-19 pandemic because COVID symptoms can lead to psychological distress including anxiety. Hericium erinaceus mycelium has been widely i...
Sleep disturbance is one of the neurobehavioral complications of lead neurotoxicity. The present study evaluated the impacts of chronic lead exposure on alteration of the sleep–wake cycle in association with changes of clock gene expression in the hypothalamus. Sprague–Dawley rats with chronic lead exposure consumed drinking water that contained 25...
Treatment options for Dravet syndrome are limited. The aim of this study was to evaluate the antiepileptic effect of the AMPA receptor antagonist perampanel (PER) on a mouse model of Dravet syndrome (Scn1a E1099X/+ ). We report here that the PER (2 mg/kg) treatment inhibited the spontaneous recurrent seizures and attenuated epileptic activity in Sc...
The present study aimed to explore whether water and ethanol extracts of Armillaria mellea mycelia produce sedative and hypnotic effects in rats. Male Sprague–Dawley rats were surgically implanted with two electroencephalogram electrodes on the skull and an electromyogram electrode on neck muscle to evaluate the alterations in rapid eye movement (R...
Researchers demonstrated an elegant ability for red discrimination in zebra finches. It is interested to understand whether red activates exhibit much stronger response than other colors in neural network levels. To reveal the question, local field potentials (LFPs) was recorded and analyzed in two visual pathways, the thalamofugal and the tectofug...
We previously demonstrated that seizure occurrences at different zeitgeber times alter sleep and circadian rhythm differently. On the other hand, the synchronized delta wave of electroencephalogram (EEG) during non-rapid eye movement (NREM) sleep facilitates seizure, while the desynchronized EEG of rapid eye movement (REM) sleep suppresses it. We a...
Adenosine exhibits a somnogenic effect; however, there is no adenosinergic hypnotic because of cardiovascular effects. This study investigated whether N6‐(4‐hydroxybenzyl) adenine riboside (T1‐11), extracted from Gastrodia elata , produces somnogenic effects in rodents. We determined the involvement of adenosine 2A receptors (A2ARs) in GABAergic ne...
Abstract Stress is one of major factors that cause sleep problems. Hypocretin represents a stress-related neuropeptide and is well known in maintaining physiological wakefulness. The hypocretinergic neurons originate in the lateral hypothalamic area (LHA) and transmit to several brain regions, including the median raphe nuclei (MRNs). The MRNs modu...
Acupuncture or electroacupuncture (EAc) exhibits various therapeutic functions, such as relieving pain, reducing inflammatory responses, and alleviating sleep disruptions. In this chapter, we discuss the neuronal mechanisms involving the electroacupuncture of bilateral Anmian (EX17) acupoints on sleep regulation. We found that administration of 20-...
Synopsis A more suitable pilocarpine rat model with microinjection into the left central nucleus of the amygdala and in-vivo diffusion tensor imaging acquisitions were used to investigate progressive changes in the white matter fibers at three different time points during epileptogenesis in temporal lobe epilepsy (TLE) with focal seizure. We found...
Objectives
Palmar hyperhidrosis (PH) exhibits excessive and unpredictable sweating. The most effective treatment for permanent cure is the ablation of thoracic sympathetic ganglia innervating hands. However, sympathectomy of T2 sympathetic ganglion by clipping or cauterization causes irreversible nerve damage, and results in a compensatory hyperhid...
Ancient Chinese literature has documented that acupuncture possesses efficient therapeutic effects on epilepsy and insomnia. There is, however, little research to reveal the possible mechanisms behind these effects. To investigate the effect of acupuncture on epilepsy and sleep, several issues need to be addressed. The first is to identify the acup...
Background
Sleep disruptions are common in epilepsy patients. Our previous study demonstrates that homeostatic factors and circadian rhythm may mediate epilepsy-induced sleep disturbances when epilepsy occurs at different zeitgeber hours. The proinflammatory cytokine, interleukin-1 (IL-1), is a somnogenic cytokine and may also be involved in epilep...
RNAseq data: gene expression in SK-N-AS cells treated with SCN1A AntagoNAT or inactive control oligonucleotide.
Video recording of a seizure in Scn1aE1099X Dravet mouse model.
RNAseq data: functional assignment of the AntagoNAT-regulated genes.
Video: In situ hybridization data showing intracellular localization of AntagoNAT in parvalbumin-positive hippocampal neurons. Green staining - parvalbumin, pink staining - AntagoNAT, blue staining - nuclei.
Dravet syndrome is a devastating genetic brain disorder caused by heterozygous loss-of-function mutation in the voltage-gated sodium channel gene SCN1A. There are currently no treatments, but the upregulation of SCN1A healthy allele represents an appealing therapeutic strategy. In this study we identified a novel, evolutionary conserved mechanism c...
The purpose of this study was to evaluate new acupuncture protocols for the clinical treatment of cervical spinal cord diseases in 19 dogs. Three treatment options containing cervical jiaji (Jing-jiaji) were developed to treat neck pain, hemiparesis, and tetraparesis depending on the severity. The interval between the neurological disease onset and...
The results of this preliminary experiment revealed overall successful rate of Palmar Hyperhidrosis (PH) post-PRF stimulation is 62.5%. We concluded that PRF, a reversible electrical stimulation is effect for PH, and most important, without side effect of CH. To avoid repeated endoscopic surgery and large volume device, we designed a miniature wire...
The positive effects of acupuncture at Feng-Chi acupoints on treating epilepsy and insomnia have been well-documented in ancient Chinese literature. However, there is a lack of scientific evidence to elucidate the underlying mechanisms behind these effects. Our previous study demonstrated that high-frequency (100 Hz) electroacupuncture (EA) at Feng...
Dravet syndrome (DS) is characterized by severe infant-onset myoclonic epilepsy along with delayed psychomotor development and heightened premature mortality. A primary monogenic cause is mutation of the SCN1A gene, which encodes the voltage-gated sodium channel subunit Nav1.1. The nature and timing of changes caused by SCN1A mutation in the hippoc...
Background. Extracorporeal shock wave lithotripsy (ESWL) is the preferred option for urolithiasis treatment. However, intensities of pain may be induced and the sedative anesthetic or analgesics were usually needed. The aim of this study was to develop an improved acupuncture-assisted anesthesia approach in pain relief. Methods. We conducted a sing...
Clinical and experimental evidence demonstrates that sleep and epilepsy reciprocally affect each other. Previous studies indicated that epilepsy alters sleep homeostasis; in contrast, sleep disturbance deteriorates epilepsy. If a therapy possesses both epilepsy suppression and sleep improvement, it would be the priority choice for seizure control....
The effect of seizure suppression by acupuncture of Feng-Chi (GB20) acupoints has been documented in the ancient Chinese literature, Lingshu Jing (Classic of the Miraculous Pivot), however, there is a lack of scientific evidence to prove it. This current study was designed to elucidate the effect of electroacupuncture (EA) stimulation of bilateral...
Theta rhythms generated in the hippocampus are controlled by the pacemaker in the medial septum-diagonal band of Broca (MS-DBB). The median raphe nucleus (MRN) transmits serotonergic signals to the MS-DBB, which suppresses the septo-hippocampus-produced theta waves, whereas GABAergic interneurons in the MRN facilitate the generation of theta oscill...
Purpose:
Bilateral electrical stimulation of anterior nuclei of thalamus (ANT) has shown promising effects on epileptic seizures. However, bilateral implantation increases the risk of surgical complications and side effects. This study was undertaken to access the effectiveness of a stimulation paradigm involving high frequency and low intensity c...
Controversial sleep disruptions (e.g., poor nighttime sleep and daytime somnolence) are common in epilepsy patients. Sleep is known to be regulated by homeostatic factors, which mediate sleep propensity, and the circadian oscillator, a clocklike mechanism. However, it is unknown how epileptic episodes that occur at different zeitgeber times (ZTs) a...
Our study investigated the role of circadian rhythm in the pathogenesis of sleep disturbance in patients with chronic kidney disease (CKD) based on an animal model.
Sixteen Sprague-Dawley (SD) rats (eight from 5/6 nephrectomized CKD group and eight from control group) were used for electroencephalography (EEG) and electromyography (EMG) recording....
The frequency of electroencephalograms (EEGs) is predominant in theta rhythm during stress (e.g., footshock) in rats. Median raphe nucleus (MRN) desynchronizes hippocampal theta waves via activation of GABAergic neurons in the medial septum-diagonal band of Broca (MS-DBB), a theta rhythm pacemaker. Increased hypocretin mediates stress responses in...
Previous results demonstrated that 10 Hz electroacupuncture (EA) of Anmian acupoints in rats during the dark period enhances slow wave sleep (SWS), which involves the induction of cholinergic activity in the caudal nucleus tractus solitarius (NTS) and subsequent activation of opioidergic neurons and μ-receptors. Studies have shown that different ki...
Aim of the study:
Baicalin is an active compound originating from the root of Scutellaria baicalensis Georgi, which has been used for anti-inflammation, anti-bacteria, anti-hypertension, anti-allergy and sedation since ancient China, though the neuronal mechanisms involved in the sedative effect is still unclear. Baicalin possesses the ability to...
Electroacupuncture (EA) possesses various therapeutic effects, including alleviation of pain, reduction of inflammation and improvement of sleep disturbance. The mechanisms of EA on sleep improvement, however, remain to be determined. It has been stated in ancient Chinese literature that the Anmian (EX17) acupoint is one of the trigger points that...
Daytime somnolence is common in patients with Parkinson's disease (PD); however there is a lack of understanding of the cellular mechanisms involved in mediating these effects. It has been hypothesized that microglial activation and the subsequent increase of pro-inflammatory cytokines play an important role in the pathogenesis of PD. Because some...
Cannabidiol (CBD) is one of the psycho-inactive constituents of marijuana, the Cannabis sativa. The pharma-cological property of CBD, especially the anxiolytic effect, is significant in the therapeutic purposes. The central nucleus of amygdala (CeA) plays a key role in the anxiety and its related behavioral responses (e.g. sleep-wake activity), and...
Methamphetamine is a widely abused psychostimulant. Abusing methamphetamine causes various adverse effects, such as immune dysfunction. The present study investigated the effect of diazepam, a central depressant, on methamphetamine-induced immunosuppression. BALB/c mice were daily administered with diazepam and methamphetamine (5mg/kg of each), eit...
Movement-related cortical potentials (MRCP; nomenclature of MRCP components according to Shibasaki and Hallett (Shibasaki H, Hallett M. What is the Bereitschaftspotential? Clin Neurophysiol 2006;117:2341-56) were studied in patients with Machado-Joseph disease (MJD) to elucidate the pathophysiology of voluntary movement.
We studied nine genetically...
Sedative-hypnotic medications, including benzodiazepines and non-benzodiazepines, are usually prescribed for the insomniac patients; however, the addiction, dependence and adverse effects of those medications have drawn much attention. In contrast, suanzaorentang, a traditional Chinese herb remedy, has been efficiently used for insomnia relief in C...
Recently, the pathogenesis of Parkinson disease (PD) has been focused on microglial activation, especially the subsequent increase of cytokines. A body of clinical evidence suggests that sleep is altered in patients with PD; however, there is a lack of understanding of the basic cellular mechanism. This study was designed to elucidate the influence...
The sedative-hypnotic medications, including benzodiazepines and non-benzodiazepines, are the most common treatments for insomnia. However, concerns regarding patterns of inappropriate use, dependence and adverse effects have led to caution in prescribing those sedative-hypnotic medications. On the other hand, a traditional Chinese herb remedy, sua...
Movement-related cortical potential (MRCP) is recorded to investigate the cerebral motor preparation in two patients with subcortical heterotopia. Magnetic resonance imaging (MRI) studies were conducted in the two patients. Scalp MRCP elicited by self-paced voluntary extension of the wrist was recorded. The MRCP waveforms and the potential maps wer...
Holmes tremor is a rare symptomatic slow tremor in the proximal parts of the limbs. It may be present at rest or maintenance of a posture, or during the movement of the affected limb. We describe herein three patients of Holmes tremor with possible etiologies of brainstem infarction and head injury. The intervals between the causal events and the a...
Surgical lesions in the medial pallidum have been shown to ameliorate motor deficits in patients with Parkinson's disease (PD). It is believed that interruption of the pallidothalamocortical projections to the motor cortex is required for the satisfactory results. In this report, we adopt cortico-cortical inhibition as the tool to assess the pallid...
The authors report a Taiwanese family with autosomal recessive hyperekplexia. Two novel mutations, W96C (from the paternal allele) and R344X (from the maternal allele), which are located in exon 4 and exon 7 of the GLRA1 gene, were identified in this family. A series of electrophysiologic investigations were conducted in one of the probands, and th...
Electroacupuncture (EAc) possesses a broad therapeutic effect, including improvement of sleep disturbances. The mechanism of sleep improvement with EAc, however, is still unclear. The present study investigated the effects of EAc stimulation of 'Anmian (extra)' acupoints on sleep organization and the implication of an active structure, the caudal n...
Clinical and experimental observations argue that sleep disturbances are common and coexist in patients with epilepsy. Our previous observations have suggested that neural-immune interactions between corticotropin-releasing hormone (CRH) and interleukin-1 (IL-1) are involved in the regulation of physiological sleep-wake behavior. In the present stu...
Evidence in the past decade indicates that the mechanisms of anti-nociception of electroacupuncture (EAc) involve actions of neuropeptides (i.e., enkephalin and endorphin) and monoamines (i.e., serotonin and norepinephrine) in the central nervous system. Our present results using a subcutaneous injection of formalin to test pain sensation in mice p...
We have previously hypothesized that corticotropin-releasing hormone (CRH) is involved in the regulation of physiological waking. In this study, we tested the hypothesis that reduction of CRH peptide would reduce spontaneous wakefulness of rats. We administered intracerebroventricularly into rats at several circadian time points antisense or sense...
While the cause of Parkinson's disease (PD) remains unknown, recent evidence suggests certain environmental factors, such as well water drinking, herbicides and pesticides exposure, and neurotoxins, may trigger the chain of oxidative reactions culminating in the death of dopaminergic neurons in substantia nigra to cause parkinsonism. Most studies t...
Corticotropin-releasing hormone (CRH) mediates responses to a variety of stressors. We subjected rats to a 1-h period of an acute stressor, physical restraint, and determined the impact on subsequent sleep-wake behavior. Restraint at the beginning of the light period, but not the dark period, increased waking and reduced rapid eye movement sleep wi...
Corticotropin-releasing hormone (CRH), expressed in widely distributed regions of the central nervous system (CNS), mediates the hypothalamic-pituitary-adrenal (HPA) axis and autonomic components of responses to stressors. Sleep, a fundamental CNS process, is altered in response to a variety of stressors. Although there is an extensive literature o...
We hypothesize that corticotropin-releasing hormone (CRH), a regulator of the hypothalamic-pituitary-adrenal (HPA) axis, is involved in sleep-wake regulation on the basis of observations that the CRH receptor antagonist astressin, after a delay of several hours, reduces waking and increases slow-wave sleep (SWS) in rats. This delay suggests a casca...
We have previously hypothesized that corticotropin-releasing hormone (CRH) is involved in the regulation of physiological waking. Central administration of CRH receptor antagonists reduces spontaneous waking in the rat. Some of the responses to central administration of CRH receptor antagonists may be mediated by mechanisms involving the hypothalam...
We have previously hypothesized that corticotropin-releasing hormone (CRH) is involved in the regulation of physiological waking. To further elucidate this role for CRH, we administered intracerebroventricularly into rats two specific CRH-receptor antagonists, alpha-helical CRH-(9-41) (alpha-hCRH) or astressin, and determined changes in electroence...
The frequency-dependent long-term modifications of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSPNMDA) was studied. Intracellular recordings were obtained from CA1 cells of rat hippocampal slices and in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and bicuculline...
The mechanism responsible for long-term depression (LTD) of pharmacologically isolated N-methyl-D-aspartate (NMDA) receptor-mediated excitatory postsynaptic potential (EPSPNMDA) was studied. Intracellular recordings were made from CA1 cells of rat hippocampal slices in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (10 M) and picrotoxin (50 M...
A single stimulus applied to the endopyriform nucleus evoked in 35 of the 101 basolateral amygdaloid (BLA) neurons a slow excitatory postsynaptic potential (s-EPSP) of varying latencies. The s-EPSP could be graded by changing the stimulus intensity and, on reaching the threshold, triggered action potentials. At stimulus intensity just subthreshold...
An in vitro slice preparation of rat amygdala was used to study the long-term modifications of synaptic efficacy following high-frequency stimulation of the ventral endopyriform nucleus. Delivery of brief tetani to the afferent fibers led to a long-term potentiation (LTP) of the amplitude and the initial slope of excitatory postsynaptic potential (...
The pharmacological properties of synaptic responses in rat basolateral amygdaloid (BLA) neurons were studied using intracellular recording techniques. Three distinct types of synaptic potential were evoked by stimulation of the adjacent ventral endopyriform nucleus: 1) a fast excitatory postsynaptic potential (f-EPSP); 2) a late EPSP (1-EPSP) foll...
The involvement of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the epileptiform activity, induced by bicuculline, was studied in slices of amygdala in the rat, using intracellular recording techniques. Stimulation of the ventral endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP). After exposure to bicuculline (20 micr...
The effect of ketamine on the paroxysmal depolarizing shift (PDS) induced by bicuculline was studied in rat amygdala slices using intracellular recording techniques. Stimulation of the ventral endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP). After exposure to bicuculline (20 microM), the same stimulus intensity evoked burst...
The involvement of the N-methyl-D-aspartate (NMDA) receptor in the epileptiform activity induced by 4-aminopyridine (4-AP) was studied in rat amygdala slices using intracellular recording techniques. Stimulation of the ventral endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP). After exposure to 4-AP (200 microM) the amygdala s...
