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Fulltext Electrical stimulation alleviates depressive-like behaviors of rats: investigation of brain targets and potential mechanisms

Lim LW, Prickaerts J, Huguet G, Kadar E, Hartung H, Sharp T, et al.

Transl Psychiatry, 2015;5:e535.
PMID: 25826110 DOI: 10.1038/tp.2015.24

Deep brain stimulation (DBS) is a promising therapy for patients with refractory depression. However, key questions remain with regard to which brain target(s) should be used for stimulation, and which mechanisms underlie the therapeutic effects. Here, we investigated the effect of DBS, with low- and high-frequency stimulation (LFS, HFS), in different brain regions (ventromedial prefrontal cortex, vmPFC; cingulate cortex, Cg; nucleus accumbens (NAc) core or shell; lateral habenula, LHb; and ventral tegmental area) on a variety of depressive-like behaviors using rat models. In the naive animal study, we found that HFS of the Cg, vmPFC, NAc core and LHb reduced anxiety levels and increased motivation for food. In the chronic unpredictable stress model, there was a robust depressive-like behavioral phenotype. Moreover, vmPFC HFS, in a comparison of all stimulated targets, produced the most profound antidepressant effects with enhanced hedonia, reduced anxiety and decreased forced-swim immobility. In the following set of electrophysiological and histochemical experiments designed to unravel some of the underlying mechanisms, we found that vmPFC HFS evoked a specific modulation of the serotonergic neurons in the dorsal raphe nucleus (DRN), which have long been linked to mood. Finally, using a neuronal mapping approach by means of c-Fos expression, we found that vmPFC HFS modulated a brain circuit linked to the DRN and known to be involved in affect. In conclusion, HFS of the vmPFC produced the most potent antidepressant effects in naive rats and rats subjected to stress by mechanisms also including the DRN.

Matched MeSH terms: Brain/physiopathology*
Electroencephalography-detected neurophysiology of internet addiction disorder and internet gaming disorder in adolescents - A review

Sharifat H, Suppiah S

Med J Malaysia, 2021 05;76(3):401-413.
PMID: 34031341

INTRODUCTION: Internet Addiction Disorder (IAD) is an umbrella term for various types of Internet-based behavioural addiction, whereas Internet Gaming Disorder (IGD) addresses a specific type of IAD that is postulated to be due to a lack of control in impulse inhibition. IGD is an area of concern in the Diagnostic and Statistics Manual of Mental Disorders (DSM-5), which can be objectively assessed by dysfunctional behaviour and the increasing time of being online, particularly during the COVID-19 pandemic. Electroencephalography (EEG) identifies amplitude changes in the evoked response potential (ERP) among IGDs, correlated with underlying comorbidities.
MATERIALS AND METHODS: A scoping review was performed to elaborate on the research regarding resting-state EEG and task-based EEG, particularly for Go/No-go paradigms pertaining to subjects with IAD or specifically IGD. The role of EEG was identified in its diagnostic capability to identify the salient changes that occurred in the response to reward network and the executive control network, using restingstate and task-based EEG. The implication of using EEG in monitoring the therapy for IAD and IGD was also reviewed.
RESULTS: EEG generally revealed reduced beta waves and increased theta waves in addicts. IGD with depression demonstrated increased theta and decreased alpha waves. Whereas increased P300, a late cognitive ERP component, was frequently associated with impaired excessive allocation of attentional resources of the IAD towards addiction-specific cues. IGD had increased whole brain delta waves at baseline, which showed significant reduction post therapy.
CONCLUSION: EEG can identify distinct neurophysiological changes among Internet Addiction Disorder and Internet Gaming Disorder that are akin to substance abuse disorders.

Matched MeSH terms: Brain/physiopathology*
Xanthone-enriched fraction of Garcinia mangostana and α-mangostin improve the spatial learning and memory of chronic cerebral hypoperfusion rats

Tiang N, Ahad MA, Murugaiyah V, Hassan Z

J Pharm Pharmacol, 2020 Nov;72(11):1629-1644.
PMID: 32743849 DOI: 10.1111/jphp.13345

OBJECTIVES: Xanthones isolated from the pericarp of Garcinia mangostana has been reported to exhibit neuroprotective effect.
METHODS: In this study, the effect of xanthone-enriched fraction of Garcinia mangostana (XEFGM) and α-mangostin (α-MG) were investigated on cognitive functions of the chronic cerebral hypoperfusion (CCH) rats.
KEY FINDINGS: HPLC analysis revealed that XEFGM contained 55.84% of α-MG. Acute oral administration of XEFGM (25, 50 and 100 mg/kg) and α-MG (25 and 50 mg/kg) before locomotor activity and Morris water maze (MWM) tests showed no significant difference between the groups for locomotor activity.
CONCLUSIONS: However, α-MG (50 mg/kg) and XEFGM (100 mg/kg) reversed the cognitive impairment induced by CCH in MWM test. α-MG (50 mg/kg) was further tested upon sub-acute 14-day treatment in CCH rats. Cognitive improvement was shown in MWM test but not in long-term potentiation (LTP). BDNF but not CaMKII was found to be down-regulated in CCH rats; however, both parameters were not affected by α-MG. In conclusion, α-MG ameliorated learning and memory deficits in both acute and sub-acute treatments in CCH rats by improving the spatial learning but not hippocampal LTP. Hence, α-MG may be a promising lead compound for CCH-associated neurodegenerative diseases, including vascular dementia and Alzheimer's disease.

Matched MeSH terms: Brain/physiopathology
Emotion processing in Parkinson's disease: an EEG spectral power study

Yuvaraj R, Murugappan M, Omar MI, Ibrahim NM, Sundaraj K, Mohamad K, et al.

Int J Neurosci, 2014 Jul;124(7):491-502.
PMID: 24168328 DOI: 10.3109/00207454.2013.860527

Although an emotional deficit is a common finding in Parkinson's disease (PD), its neurobiological mechanism on emotion recognition is still unknown. This study examined the emotion processing deficits in PD patients using electroencephalogram (EEG) signals in response to multimodal stimuli.

Matched MeSH terms: Brain/physiopathology*
Brain biometals and Alzheimer's disease - boon or bane?

Prakash A, Dhaliwal GK, Kumar P, Majeed AB

Int J Neurosci, 2017 Feb;127(2):99-108.
PMID: 27044501

Alzheimer's disease (AD) is the most common form of dementia. Several hypotheses have been put forward to explain the basis of disease onset and progression. A complicated array of molecular events has been implicated in the pathogenesis of AD. It is attributed to a variety of pathological conditions that share similar critical processes, such as oxidative stress, proteinaceous aggregations, mitochondrial dysfunctions and energy failure. There is increasing evidence suggesting that metal homeostasis is dysregulated in the pathology of AD. Biometals play an important role in the normal body functioning but AD may be mediated or triggered by disproportion of metal ions leading to changes in critical biological systems and initiating a cascade of events finally leading to neurodegeneration and cell death. The link is multifactorial, and although the source of the shift in oxidative homeostasis is still unclear, current evidence points to changes in the balance of redox transition metals, especially iron, copper (Cu) and other trace metals. Their levels in the brain are found to be elevated in AD. In other neurodegenerative disorders, Cu, zinc, aluminum and manganese are involved. This paper is a review of recent advances of the role of metals in the pathogenesis and pathophysiology of AD and related neurodegenerative diseases.

Matched MeSH terms: Brain/physiopathology
Fulltext Validating a functional near-infrared spectroscopy diagnostic paradigm for Major Depressive Disorder

Husain SF, Yu R, Tang TB, Tam WW, Tran B, Quek TT, et al.

Sci Rep, 2020 06 16;10(1):9740.
PMID: 32546704 DOI: 10.1038/s41598-020-66784-2

Reduced haemodynamic response in the frontotemporal cortices of patients with major depressive disorder (MDD) has been demonstrated using functional near-infrared spectroscopy (fNIRS). Most notably, changes in cortical oxy-haemoglobin during a Japanese phonetic fluency task can differentiate psychiatric patients from healthy controls (HC). However, this paradigm has not been validated in the English language. Therefore, the present work aimed to distinguish patients with MDD from HCs, using haemodynamic response measured during an English letter fluency task. One hundred and five HCs and 105 patients with MDD took part in this study. NIRS signals during the verbal fluency task (VFT) was acquired using a 52-channel system, and changes in oxy-haemoglobin in the frontal and temporal regions were quantified. Depression severity, psychosocial functioning, pharmacotherapy and psychiatric history were noted. Patients with MDD had smaller changes in oxy-haemoglobin in the frontal and temporal cortices than HCs. In both regions of interest, oxy-haemoglobin was not associated with any of the clinical variables studied. 75.2% and 76.5% of patients with MDD were correctly classified using frontal and temporal region oxy-haemoglobin, respectively. Haemodynamic response measured by fNIRS during an English letter fluency task is a promising biomarker for MDD.

Matched MeSH terms: Brain/physiopathology
Fulltext Pneumocephalus and air travel: an experimental investigation on the effects of aircraft cabin pressure on intracranial pressure

Lim E, Lan BL, Ooi EH, Low HL

Sci Rep, 2020 08 12;10(1):13626.
PMID: 32788610 DOI: 10.1038/s41598-020-70614-w

This study investigates the effects of aircraft cabin pressure on intracranial pressure (ICP) elevation of a pneumocephalus patient. We propose an experimental setup that simulates the intracranial hydrodynamics of a pneumocephalus patient during flight. It consists of an acrylic box (skull), air-filled balloon [intracranial air (ICA)], water-filled balloon (cerebrospinal fluid and blood) and agarose gel (brain). The cabin was replicated using a custom-made pressure chamber. The setup can measure the rise in ICP during depressurization to levels similar to that inside the cabin at cruising altitude. ΔICP, i.e. the difference between mean cruising ICP and initial ICP, was found to increase with ICA volume and ROC. However, ΔICP was independent of the initial ICP. The largest ΔICP was 5 mmHg; obtained when ICA volume and ROC were 20 ml and 1,600 ft/min, respectively. The postulated ICA expansion and the subsequent increase in ICP in pneumocephalus patients during flight were successfully quantified in a laboratory setting. Based on the quantitative and qualitative analyses of the results, an ICA volume of 20 ml and initial ICP of 15 mmHg were recommended as conservative thresholds that are required for safe air travel among pneumocephalus patients. This study provides laboratory data that may be used by doctors to advise post-neurosurgical patients if they can safely fly.

Matched MeSH terms: Brain/physiopathology
Acute effects of methadone on EEG power spectrum and event-related potentials among heroin dependents

Motlagh F, Ibrahim F, Rashid R, Shafiabady N, Seghatoleslam T, Habil H

Psychopharmacology (Berl), 2018 Nov;235(11):3273-3288.
PMID: 30310960 DOI: 10.1007/s00213-018-5035-0

Methadone as the most prevalent opioid substitution medication has been shown to influence the neurophysiological functions among heroin addicts. However, there is no firm conclusion on acute neuroelectrophysiological changes among methadone-treated subjects as well as the effectiveness of methadone in restoring brain electrical abnormalities among heroin addicts. This study aims to investigate the acute and short-term effects of methadone administration on the brain's electrophysiological properties before and after daily methadone intake over 10 weeks of treatment among heroin addicts. EEG spectral analysis and single-trial event-related potential (ERP) measurements were used to investigate possible alterations in the brain's electrical activities, as well as the cognitive attributes associated with MMN and P3. The results confirmed abnormal brain activities predominantly in the beta band and diminished information processing ability including lower amplitude and prolonged latency of cognitive responses among heroin addicts compared to healthy controls. In addition, the alteration of EEG activities in the frontal and central regions was found to be associated with the withdrawal symptoms of drug users. Certain brain regions were found to be influenced significantly by methadone intake; acute effects of methadone induction appeared to be associative to its dosage. The findings suggest that methadone administration affects cognitive performance and activates the cortical neuronal networks, resulting in cognitive responses enhancement which may be influential in reorganizing cognitive dysfunctions among heroin addicts. This study also supports the notion that the brain's oscillation powers and ERPs can be utilized as neurophysiological indices for assessing the addiction treatment traits.

Matched MeSH terms: Brain/physiopathology
Fulltext A systems biology approach towards the identification of candidate therapeutic genes and potential biomarkers for Parkinson's disease

Sakharkar MK, Kashmir Singh SK, Rajamanickam K, Mohamed Essa M, Yang J, Chidambaram SB

PLoS One, 2019;14(9):e0220995.
PMID: 31487305 DOI: 10.1371/journal.pone.0220995

Parkinson's disease (PD) is an irreversible and incurable multigenic neurodegenerative disorder. It involves progressive loss of mid brain dopaminergic neurons in the substantia nigra pars compacta (SN). We compared brain gene expression profiles with those from the peripheral blood cells of a separate sample of PD patients to identify disease-associated genes. Here, we demonstrate the use of gene expression profiling of brain and blood for detecting valid targets and identifying early PD biomarkers. Implementing this systematic approach, we discovered putative PD risk genes in brain, delineated biological processes and molecular functions that may be particularly disrupted in PD and also identified several putative PD biomarkers in blood. 20 of the differentially expressed genes in SN were also found to be differentially expressed in the blood. Further application of this methodology to other brain regions and neurological disorders should facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for PD. The identification of valid peripheral biomarkers for PD may ultimately facilitate early identification, intervention, and prevention efforts as well.

Matched MeSH terms: Brain/physiopathology
Fulltext A wavelet-based technique to predict treatment outcome for Major Depressive Disorder

Mumtaz W, Xia L, Mohd Yasin MA, Azhar Ali SS, Malik AS

PLoS One, 2017;12(2):e0171409.
PMID: 28152063 DOI: 10.1371/journal.pone.0171409

Treatment management for Major Depressive Disorder (MDD) has been challenging. However, electroencephalogram (EEG)-based predictions of antidepressant's treatment outcome may help during antidepressant's selection and ultimately improve the quality of life for MDD patients. In this study, a machine learning (ML) method involving pretreatment EEG data was proposed to perform such predictions for Selective Serotonin Reuptake Inhibitor (SSRIs). For this purpose, the acquisition of experimental data involved 34 MDD patients and 30 healthy controls. Consequently, a feature matrix was constructed involving time-frequency decomposition of EEG data based on wavelet transform (WT) analysis, termed as EEG data matrix. However, the resultant EEG data matrix had high dimensionality. Therefore, dimension reduction was performed based on a rank-based feature selection method according to a criterion, i.e., receiver operating characteristic (ROC). As a result, the most significant features were identified and further be utilized during the training and testing of a classification model, i.e., the logistic regression (LR) classifier. Finally, the LR model was validated with 100 iterations of 10-fold cross-validation (10-CV). The classification results were compared with short-time Fourier transform (STFT) analysis, and empirical mode decompositions (EMD). The wavelet features extracted from frontal and temporal EEG data were found statistically significant. In comparison with other time-frequency approaches such as the STFT and EMD, the WT analysis has shown highest classification accuracy, i.e., accuracy = 87.5%, sensitivity = 95%, and specificity = 80%. In conclusion, significant wavelet coefficients extracted from frontal and temporal pre-treatment EEG data involving delta and theta frequency bands may predict antidepressant's treatment outcome for the MDD patients.

Matched MeSH terms: Brain/physiopathology
Fulltext The metastable brain associated with autistic-like traits of typically developing individuals

Sase T, Kitajo K

PLoS Comput Biol, 2021 04;17(4):e1008929.
PMID: 33861737 DOI: 10.1371/journal.pcbi.1008929

Metastability in the brain is thought to be a mechanism involved in the dynamic organization of cognitive and behavioral functions across multiple spatiotemporal scales. However, it is not clear how such organization is realized in underlying neural oscillations in a high-dimensional state space. It was shown that macroscopic oscillations often form phase-phase coupling (PPC) and phase-amplitude coupling (PAC), which result in synchronization and amplitude modulation, respectively, even without external stimuli. These oscillations can also make spontaneous transitions across synchronous states at rest. Using resting-state electroencephalographic signals and the autism-spectrum quotient scores acquired from healthy humans, we show experimental evidence that the PAC combined with PPC allows amplitude modulation to be transient, and that the metastable dynamics with this transient modulation is associated with autistic-like traits. In individuals with a longer attention span, such dynamics tended to show fewer transitions between states by forming delta-alpha PAC. We identified these states as two-dimensional metastable states that could share consistent patterns across individuals. Our findings suggest that the human brain dynamically organizes inter-individual differences in a hierarchy of macroscopic oscillations with multiple timescales by utilizing metastability.

Matched MeSH terms: Brain/physiopathology*
Fulltext Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies

Jha NK, Sharma A, Jha SK, Ojha S, Chellappan DK, Gupta G, et al.

Open Biol, 2020 Dec;10(12):200286.
PMID: 33352062 DOI: 10.1098/rsob.200286

Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood-brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.

Matched MeSH terms: Brain/physiopathology
Fulltext A Review on the Relationship between Tocotrienol and Alzheimer Disease

Chin KY, Tay SS

Nutrients, 2018 Jul 09;10(7).
PMID: 29987193 DOI: 10.3390/nu10070881

Alzheimer’s disease (AD) is plaguing the aging population worldwide due to its tremendous health care and socioeconomic burden. Current treatment of AD only offers symptomatic relief to patients. Development of agents targeting specific pathologies of AD is very slow. Tocotrienol, a member of the vitamin E family, can tackle many aspects of AD, such as oxidative stress, mitochondrial dysfunction and abnormal cholesterol synthesis. This review summarizes the current evidence on the role of tocotrienol as a neuroprotective agent. Preclinical studies showed that tocotrienol could reduce oxidative stress by acting as a free-radical scavenger and promoter of mitochondrial function and cellular repair. It also prevented glutamate-induced neurotoxicity in the cells. Human epidemiological studies showed a significant inverse relationship between tocotrienol levels and the occurrence of AD. However, there is no clinical trial to support the claim that tocotrienol can delay or prevent the onset of AD. As a conclusion, tocotrienol has the potential to be developed as an AD-preventing agent but further studies are required to validate its efficacy in humans.

Matched MeSH terms: Brain/physiopathology
Fulltext Irritable Bowel Syndrome, Depression, and Neurodegeneration: A Bidirectional Communication from Gut to Brain

Aziz MNM, Kumar J, Muhammad Nawawi KN, Raja Ali RA, Mokhtar NM

Nutrients, 2021 Aug 31;13(9).
PMID: 34578939 DOI: 10.3390/nu13093061

Patients with irritable bowel syndrome (IBS) are increasingly presenting with a wide range of neuropsychiatric symptoms, such as deterioration in gastroenteric physiology, including visceral hypersensitivity, altered intestinal membrane permeability, and gastrointestinal motor dysfunction. Functional imaging of IBS patients has revealed several abnormalities in various brain regions, such as significant activation of amygdala, thinning of insular and anterior cingulate cortex, and increase in hypothalamic gray matter, which results in poor psychiatric and cognitive outcomes. Interrelations between the enteric and central events in IBS-related gastrointestinal, neurological, and psychiatric pathologies have compelled researchers to study the gut-brain axis-a bidirectional communication that maintains the homeostasis of the gastrointestinal and central nervous system with gut microbiota as the protagonist. Thus, it can be disrupted by any alteration owing to the gut dysbiosis or loss of diversity in microbial composition. Available evidence indicates that the use of probiotics as a part of a balanced diet is effective in the management of IBS and IBS-associated neurodegenerative and psychiatric comorbidities. In this review, we delineate the pathogenesis and complications of IBS from gastrointestinal and neuropsychiatric standpoints while also discussing the neurodegenerative events in enteric and central nervous systems of IBS patients and the therapeutic potential of gut microbiota-based therapy established on clinical and preclinical data.

Matched MeSH terms: Brain/physiopathology
6-OHDA-Lesioned Adult Zebrafish as a Useful Parkinson's Disease Model for Dopaminergic Neuroregeneration

Vijayanathan Y, Lim FT, Lim SM, Long CM, Tan MP, Majeed ABA, et al.

Neurotox Res, 2017 Oct;32(3):496-508.
PMID: 28707266 DOI: 10.1007/s12640-017-9778-x

Conventional mammalian models of neurodegeneration are often limited by futile axonogenesis with minimal functional recuperation of severed neurons. The emergence of zebrafish, a non-mammalian model with excellent neuroregenerative properties, may address these limitations. This study aimed to establish an adult zebrafish-based, neurotoxin-induced Parkinson's disease (PD) model and subsequently validate the regenerative capability of dopaminergic neurons (DpN). The DpN of adult male zebrafish (Danio rerio) were lesioned by microinjecting 6-hydroxydopamine (6-OHDA) neurotoxin (6.25, 12.5, 18.75, 25, 37.5, 50 and 100 mg/kg) into the ventral diencephalon (Dn). This was facilitated by an optimised protocol that utilised 1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanineperchlorate (DiI) dye to precisely identify the injection site. Immunostaining was utilised to identify the number of tyrosine hydroxylase immunoreactive (TH-ir) DpN in brain regions of interest (i.e. olfactory bulb, telencephalon, preoptic area, posterior tuberculum and hypothalamus). Open tank video recordings were performed for locomotor studies. The Dn was accessed by setting the injection angle of the microinjection capillary to 60° and injection depth to 1200 μm (from the exposed brain surface). 6-OHDA (25 mg/kg) successfully ablated >85% of the Dn DpN (preoptic area, posterior tuberculum and hypothalamus) whilst maintaining a 100% survival. Locomotor analysis of 5-min recordings revealed that 6-OHDA-lesioned adult zebrafish were significantly (p

Matched MeSH terms: Brain/physiopathology
Combination of transcranial direct current stimulation and methylphenidate in subacute stroke

Wang QM, Cui H, Han SJ, Black-Schaffer R, Volz MS, Lee YT, et al.

Neurosci Lett, 2014 May 21;569:6-11.
PMID: 24631567 DOI: 10.1016/j.neulet.2014.03.011

Noninvasive transcranial direct current stimulation (tDCS) and methylphenidate (MP) are associated with motor recovery after stroke. Based on the potentially complementary mechanisms of these interventions, we examined whether there is an interactive effect between MP and tDCS. In this preliminary study, we randomized subacute stroke subjects to receive tDCS alone, MP alone or combination of tDCS and MP. A blinded rater measured safety, hand function, and cortical excitability before and after treatment. None of the treatments caused any major or severe adverse effects or induced significant differences in cortical excitability. Analysis of variance of gain score, as measured by Purdue pegboard test, showed a significant between-group difference (F(2,6)=12.167, p=0.008). Post hoc analysis showed that the combination treatment effected greater Purdue pegboard gain scores than tDCS alone (p=0.017) or MP alone (p=0.01). Our preliminary data with nine subjects shows an interesting dissociation between motor function improvement and lack of motor corticospinal plasticity changes as indexed by transcranial magnetic stimulation in subacute stroke subjects.

Matched MeSH terms: Brain/physiopathology
Fulltext Overlap of Bickerstaff brainstem encephalitis/Guillain-Barré syndrome simulating brain death

Tan CY, Ahmad SB, Goh KJ, Latif LA, Shahrizaila N

Neurol India, 2018 9 21;66(5):1475-1480.
PMID: 30233023 DOI: 10.4103/0028-3886.241342
Matched MeSH terms: Brain/physiopathology
Fulltext Altered trajectories of neurodevelopment and behavior in mouse models of Rett syndrome

Smith ES, Smith DR, Eyring C, Braileanu M, Smith-Connor KS, Ei Tan Y, et al.

Neurobiol Learn Mem, 2019 Nov;165:106962.
PMID: 30502397 DOI: 10.1016/j.nlm.2018.11.007

Rett Syndrome (RTT) is a genetic disorder that is caused by mutations in the x-linked gene coding for methyl-CpG-biding-protein 2 (MECP2) and that mainly affects females. Male and female transgenic mouse models of RTT have been studied extensively, and we have learned a great deal regarding RTT neuropathology and how MeCP2 deficiency may be influencing brain function and maturation. In this manuscript we review what is known concerning structural and coinciding functional and behavioral deficits in RTT and in mouse models of MeCP2 deficiency. We also introduce our own corroborating data regarding behavioral phenotype and morphological alterations in volume of the cortex and striatum and the density of neurons, aberrations in experience-dependent plasticity within the barrel cortex and the impact of MeCP2 loss on glial structure. We conclude that regional structural changes in genetic models of RTT show great similarity to the alterations in brain structure of patients with RTT. These region-specific modifications often coincide with phenotype onset and contribute to larger issues of circuit connectivity, progression, and severity. Although the alterations seen in mouse models of RTT appear to be primarily due to cell-autonomous effects, there are also non-cell autonomous mechanisms including those caused by MeCP2-deficient glia that negatively impact healthy neuronal function. Collectively, this body of work has provided a solid foundation on which to continue to build our understanding of the role of MeCP2 on neuronal and glial structure and function, its greater impact on neural development, and potential new therapeutic avenues.

Matched MeSH terms: Brain/physiopathology
Periodic lateralized epileptiform discharges in neuropsychiatric lupus: association with cerebritis in magnetic resonance imaging and resolution after intravenous immunoglobulin

Lim KS, Cheong KL, Tan CT

Lupus, 2010 May;19(6):748-52.
PMID: 20133346 DOI: 10.1177/0961203309351539

A 13-year-old girl with a known diagnosis of systemic lupus erythematosus presented with seizures and psychosis. An electroencephalogram (EEG) revealed continuous, non-evolving periodic lateralized epileptiform discharges (PLEDs) in the left temporal region, which did not resolve with benzodiazepine. A magnetic resonance imaging (MRI) brain scan demonstrated a focal hyperintensity in the left medial temporal and left occipital lobes, left thalamus and bilateral cerebellar white matter, with evidence of vasculitis in the magnetic resonance angiography. Intravenous immunoglobulin was given because of failed steroid therapy, which resulted in a full resolution of clinical, EEG and MRI abnormalities. Lupus cerebritis should be considered as a possible aetiology in PLEDs, and immunoglobulin can be effective in neuropsychiatric lupus.

Matched MeSH terms: Brain/physiopathology
Fulltext Functional dyspepsia

Ford AC, Mahadeva S, Carbone MF, Lacy BE, Talley NJ

Lancet, 2020 11 21;396(10263):1689-1702.
PMID: 33049222 DOI: 10.1016/S0140-6736(20)30469-4

Dyspepsia is a complex of symptoms referable to the gastroduodenal region of the gastrointestinal tract and includes epigastric pain or burning, postprandial fullness, or early satiety. Approximately 80% of individuals with dyspepsia have no structural explanation for their symptoms and have functional dyspepsia. Functional dyspepsia affects up to 16% of otherwise healthy individuals in the general population. Risk factors include psychological comorbidity, acute gastroenteritis, female sex, smoking, use of non-steroidal anti-inflammatory drugs, and Helicobacter pylori infection. The pathophysiology remains incompletely understood, but it is probably related to disordered communication between the gut and the brain, leading to motility disturbances, visceral hypersensitivity, and alterations in gastrointestinal microbiota, mucosal and immune function, and CNS processing. Although technically a normal endoscopy is required to diagnose functional dyspepsia, the utility of endoscopy in all patients with typical symptoms is minimal; its use should be restricted to people aged 55 years and older, or to those with concerning features, such as weight loss or vomiting. As a result of our incomplete understanding of its pathophysiology, functional dyspepsia is difficult to treat and, in most patients, the condition is chronic and the natural history is one of fluctuating symptoms. Eradication therapy should be offered to patients with functional dyspepsia who test positive for Helicobacter pylori. Other therapies with evidence of effectiveness include proton pump inhibitors, histamine-2 receptor antagonists, prokinetics, and central neuromodulators. The role of psychological therapies is uncertain. As our understanding of the pathophysiology of functional dyspepsia increases, it is probable that the next decade will see the emergence of truly disease-modifying therapies for the first time.

Matched MeSH terms: Brain/physiopathology*

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