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Transcriptome composition of the preoptic area in mid-age and escitalopram treatment in male mice

Moriya S, Soga T, Wong DW, Parhar IS

Neurosci Lett, 2016 May 27;622:67-71.
PMID: 27113202 DOI: 10.1016/j.neulet.2016.04.052

The decrease in serotonergic neurotransmission during aging can increase the risk of neuropsychiatric diseases such as depression in elderly population and decline the reproductive system. Therefore, it is important to understand the age-associated molecular mechanisms of brain aging. In this study, the effect of aging and chronic escitalopram (antidepressant) treatment to admit mice was investigated by comparing transcriptomes in the preoptic area (POA) which is a key nucleus for reproduction. In the mid-aged brain, the immune system-related genes were increased and hormone response-related genes were decreased. In the escitalopram treated brains, transcription-, granule cell proliferation- and vasoconstriction-related genes were increased and olfactory receptors were decreased. Since homeostasis and neuroprotection-related genes were altered in both of mid-age and escitalopram treatment, these genes could be important for serotonin related physiologies in the POA.
Preconditioning effect of (S)-3,5-dihydroxyphenylglycine on ischemic injury in middle cerebral artery occluded Sprague-Dawley rats

Nik Ramli NN, Omar N, Husin A, Ismail Z, Siran R

Neurosci Lett, 2015 Feb 19;588:137-41.
PMID: 25562631 DOI: 10.1016/j.neulet.2014.12.062

Glutamate receptors are the integral cellular components associated with excitotoxicity mechanism induced by the ischemic cascade events. Therefore the glutamate receptors have become the major molecular targets of neuroprotective agents in stroke researches. Recent studies have demonstrated that a Group I metabotropic glutamate receptor agonist, (S)-3,5-dihydroxyphenylglycine ((S)-3,5-DHPG) preconditioning elicits neuroprotection in the hippocampal slice cultures exposed to toxic level of N-methyl-d-aspartate (NMDA). We further investigated the preconditioning effects of (S)-3,5-DHPG on acute ischemic stroke rats. One 10 or 100μM of (S)-3,5-DHPG was administered intrathecally to Sprague-Dawley adult male rats, 2h prior to induction of acute ischemic stroke by middle cerebral artery occlusion (MCAO). After 24h, neurological deficits were evaluated by modified stroke severity scores and grid-walking test. All rats were sacrificed and infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride staining. The serum level of neuron-specific enolase (NSE) of each rat was analyzed by enzyme-linked immunosorbent assay (ELISA). One and 10μM of (S)-3,5-DHPG preconditioning in the stroke rats showed significant improvements in motor impairment (P<0.01), reduction in the infarct volume (P<0.01) and reduction in the NSE serum level (P<0.01) compared to the control stroke rats. We conclude that 1 and 10μM (S)-3,5-DHPG preconditioning induced protective effects against acute ischemic insult in vivo.
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.
The role of tyrosine hydroxylase gene variants in suicide attempt in schizophrenia

Hu J, Chan LF, Souza RP, Tampakeras M, Kennedy JL, Zai C, et al.

Neurosci Lett, 2014 Jan 24;559:39-43.
PMID: 24275212 DOI: 10.1016/j.neulet.2013.11.025

Evidence has shown that attempted suicide in psychiatric disorders is a complex interplay of genes and environment. Noradrenergic dysfunction due to abnormalities in the tyrosine hydroxylase (TH) gene has been implicated in the pathogenesis of suicidal behavior in mood disorders. However, suicide is a leading cause of mortality in schizophrenia too. Recent evidence suggests that TH gene variants may also increase the risk of suicide attempts in schizophrenia patients, although the interaction with established clinical risk factors is unclear. This study aimed to identify TH gene variants conferring risk for suicide attempt in schizophrenia while accounting for the interaction between this gene and clinical risk factors. We performed analysis on four TH SNPs (rs11564717, rs11042950, rs2070762, rs689) and the common TCAT repeat (UniSTS:240639) for 234 schizophrenia patients (51 suicide attempters and 183 non-attempters). Clinical risk factors and ethnic stratification were included as covariates. Single marker analysis identified the SNP rs11564717 (p=0.042) and the TCAT(6) (p=0.004) as risk variants for suicide attempt. We also identified the haplotype A-A-A-G as a risk factor for suicide attempt (p=0.0025). In conclusion, our findings suggest that TH polymorphisms may contribute to the risk of attempted suicide in schizophrenia even after accounting for established clinical risk factors and ethnic stratification. Further larger scale studies are needed to confirm these findings and to understand the mechanisms underlying the role of TH gene variants in suicide attempt in schizophrenia.
Neuroprotective effect of bioflavonoid quercetin in 6-hydroxydopamine-induced oxidative stress biomarkers in the rat striatum

Haleagrahara N, Siew CJ, Mitra NK, Kumari M

Neurosci Lett, 2011 Aug 15;500(2):139-43.
PMID: 21704673 DOI: 10.1016/j.neulet.2011.06.021

An increasing large body of research on Parkinson's disease (PD) has focused on the understanding of the mechanisms behind the potential neuro protection offered by antioxidants and iron chelating agents. In this study, the protective effect of the bioflavonoid quercetin on 6-hydroxydopamine (6-OHDA)-induced model of PD was investigated. PD was induced by a single intracisternal injection of 6-hydroxydopamine (300μg) to male Sprague-Dawley rats. Quercetin treatment (30mg/kg body weight) over 14 consecutive days markedly increased the striatal dopamine and antioxidant enzyme levels compared with similar measurements in the group treated with 6-OHDA alone. There was a significant decrease in protein carbonyl content in the striatum compared with that of rats that did not receive quercetin. A significant increase in neuronal survivability was also found with quercetin treatment in rats administered 6-OHDA. In conclusion, treatment with quercetin defended against the oxidative stress in the striatum and reduced the dopaminergic neuronal loss in the rat model of PD.
Fulltext Cortical signal-in-noise coding varies by noise type, signal-to-noise ratio, age, and hearing status

Maamor N, Billings CJ

Neurosci Lett, 2017 01 01;636:258-264.
PMID: 27838448 DOI: 10.1016/j.neulet.2016.11.020

The purpose of this study was to determine the effects of noise type, signal-to-noise ratio (SNR), age, and hearing status on cortical auditory evoked potentials (CAEPs) to speech sounds. This helps to explain the hearing-in-noise difficulties often seen in the aging and hearing impaired population. Continuous, modulated, and babble noise types were presented at varying SNRs to 30 individuals divided into three groups according to age and hearing status. Significant main effects of noise type, SNR, and group were found. Interaction effects revealed that the SNR effect varies as a function of noise type and is most systematic for continuous noise. Effects of age and hearing loss were limited to CAEP latency and were differentially modulated by energetic and informational-like masking. It is clear that the spectrotemporal characteristics of signals and noises play an important role in determining the morphology of neural responses. Participant factors such as age and hearing status, also play an important role in determining the brain's response to complex auditory stimuli and contribute to the ability to listen in noise.
pink1, atp13a2 and uchl1 expressions are affected by inflammation in the brain

Moriya S, Tan VP, Yee AK, Parhar IS

Neurosci Lett, 2019 08 24;708:134330.
PMID: 31201839 DOI: 10.1016/j.neulet.2019.134330

In Parkinson's disease (PD), several genes have been identified as the PD-related genes, however, the regulatory mechanisms of these gene expressions have not been fully identified. In this study, we investigated the effect of inflammation, one of the major risk factors in PD on expressions of the PD-related genes. Lipopolysaccharide (LPS) was intraperitoneally administered to mature male zebrafish and gene expressions in the brains were examined by real-time PCR. In the inflammation-related genes, expressions of tnfb, il1b and il6 were increased at 2 days post administration in the 10 μg group, and tnfb expression was also increased at 4 days post administration in the 1 μg and 10 μg group. In the PD-related genes, pink1 expression was significantly decreased at 4 days, atp13a2 expression was significantly increased at 7 days, and uchl1 expression was significantly decreased at 7 days. This suggests that pink1, atp13a2 and uchl1 expressions are regulated by inflammation, and this regulatory mechanism might be involved in the progress of PD.
How do Asians perceive Caucasian eyes? Electrophysiological correlates of perceiving racial differences from the eyes region of the face

Yong MH, Lim XL, Schaefer A

Neurosci Lett, 2020 02 16;720:134759.
PMID: 31952988 DOI: 10.1016/j.neulet.2020.134759

Past research has found that several brain event-related potentials (ERPs) were sensitive to the perception of ethnic differences displayed on human faces. This body of research suggests that the phenomenon of "race perception" involves a cascade of cognitive processes that includes both automatic and overt attentional mechanisms. However, most of these studies used stimuli depicting whole faces rather than stimuli depicting separate facial features. Therefore, it is still largely unknown if ERP responses to racial differences are the result of a holistic processing of the whole face, or whether they can be accounted for by the perception of single facial features. To address this issue, we examined whether a single facial feature, the eyes region, can provide sufficient information to trigger known ERP correlates of race perception such as the P2, the N400 and the Late Positive Complex (LPC). Specifically, we showed pictures depicting only the eyes region of Caucasian and Asian faces to a sample of Asian participants. We found that the P2 was larger for other-race (OR) compared to same-race (SR) eyes, and that the N400 was larger for SR compared to OR eyes. The effects on the P2 may suggest an enhanced vigilance response to OR eyes whereas the N400 effect could reflect a signal of familiarity triggered by SR eyes. These results indicate that a specific facial feature, the eyes region, can account for known effects of race perception on early brain potentials. Our findings also indicate that well-known early neural correlates of race perception can be triggered in the absence of a holistic processing of the whole face.
The effects of chronic mitragynine (Kratom) exposure on the EEG in rats

Suhaimi FW, Hassan Z, Mansor SM, Müller CP

Neurosci Lett, 2021 02 06;745:135632.
PMID: 33444671 DOI: 10.1016/j.neulet.2021.135632

Mitragynine is the main alkaloid isolated from the leaves of Mitragyna speciosa Korth (Kratom). Kratom has been widely used to relieve pain and opioid withdrawal symptoms in humans but may also cause memory deficits. Here we investigated the changes in brain electroencephalogram (EEG) activity after acute and chronic exposure to mitragynine in freely moving rats. Vehicle, morphine (5 mg/kg) or mitragynine (1, 5 and 10 mg/kg) were administered for 28 days, and EEG activity was repeatedly recorded from the frontal cortex, neocortex and hippocampus. Repeated exposure to mitragynine increased delta, but decreased alpha powers in both cortical regions. It further decreased delta power in the hippocampus. These findings suggest that acute and chronic mitragynine can have profound effects on EEG activity, which may underlie effects on behavioral activity and cognition, particularly learning and memory function.
Mini review: Potential therapeutic values of mitragynine as an opioid substitution therapy

Harun N, Kamaruzaman NA, Mohamed Sofian Z, Hassan Z

Neurosci Lett, 2022 Jan 31;773:136500.
PMID: 35114335 DOI: 10.1016/j.neulet.2022.136500

Opioid use disorder (OUD) has become a significant public health issue worldwide. Methadone and buprenorphine are the most common medications used for treating OUD. These drugs have the potential to assist many patients in managing their opioid dependence and withdrawal but they are currently misused and associated with certain compliance issues, side effects, and risk of relapse. As an opioid-like herbal supplement, Mitragyna speciosa Korth or kratom has received increased attention for managing chronic pain and opioid withdrawal symptoms. Nevertheless, the use of kratom as a self-treatment medication for opioid dependence continues to be controversial due to concerns raised about its effectiveness, safety, and abuse liability. The main active alkaloid constituent of the plant, mitragynine, has been shown to act as a partial mu-opioid agonist. Given this pharmacology, studies have been focusing on this psychoactive compound to examine its potential therapeutic values as medication-assisted therapy (MAT). This review aims to provide a current preclinical overview of mitragynine as a prospective novel option for MAT and summarise the recent developments in determining if the plant's active alkaloid could provide an alternative to opioids in the treatment of OUD.
The emergence of machine learning in auditory neural impairment: A systematic review

Abu Bakar AR, Lai KW, Hamzaid NA

Neurosci Lett, 2021 11 20;765:136250.
PMID: 34536511 DOI: 10.1016/j.neulet.2021.136250

Hearing loss is a common neurodegenerative disease that can start at any stage of life. Misalignment of the auditory neural impairment may impose challenges in processing incoming auditory stimulus that can be measured using electroencephalography (EEG). The electrophysiological behaviour response emanated from EEG auditory evoked potential (AEP) requires highly trained professionals for analysis and interpretation. Reliable automated methods using techniques of machine learning would assist the auditory assessment process for informed treatment and practice. It is thus highly required to develop models that are more efficient and precise by considering the characteristics of brain signals. This study aims to provide a comprehensive review of several state-of-the-art techniques of machine learning that adopt EEG evoked response for the auditory assessment within the last 13 years. Out of 161 initially screened articles, 11 were retained for synthesis. The outcome of the review presented that the Support Vector Machine (SVM) classifier outperformed with over 80% accuracy metric and was recognized as the best suited model within the field of auditory research. This paper discussed the comprehensive iterative properties of the proposed computed algorithms and the feasible future direction in hearing impaired rehabilitation.
Real time monitoring of dopamine release evoked by mitragynine (Kratom): An insight through electrochemical sensor

Effendy MA, Yunusa S, Zain ZM, Hassan Z

Neurosci Lett, 2021 10 15;763:136183.
PMID: 34418508 DOI: 10.1016/j.neulet.2021.136183

BACKGROUND: Mitragynine, the major indole alkaloid from Mitragyna speciosa has been reported previously to possess abuse liability. However, there are insufficient data suggesting the mechanism through which this pharmacological agent causes addiction.
AIMS: In this study, we investigated the effects of mitragynine on dopamine (DA) level and dopamine transporter (DAT) expression from the rat's frontal cortex.
METHODS: DA level was recorded in the brain samples of animals treated with acute or repeated exposure for 4 consecutive days with either vehicle or mitragynine (1 and 30 mg/kg) using electrochemical sensor. Animals were then decapitated and the brain regions were removed, snap-frozen in liquid nitrogen and immediately stored at -80 °C. DA level was quantified using Enzyme linked immunosorbent assay (ELISA) kits and DAT gene expression was determined using quantitative real time polymerase chain reaction (RT-qPCR).
RESULTS/OUTCOME: Mitragynine (1 and 30 mg/kg) did not increase DA release following acute treatment, however, after repeated exposure at day 4, mitragynine significantly and dose dependently increased DA release in the frontal cortex. In this study, we also observed a significant increase in DAT mRNA expression at day 4 in group treated with mitragynine (30 mg/kg).
CONCLUSION/INTERPRETATION: Data from this study indicates that mitragynine significantly increased DA release when administered repeatedly, increased in DAT mRNA expression with the highest tested dose (30 mg/kg). Therefore, the rewarding effects observed after mitragynine administration could be due to its ability to increase DA content in certain areas of the brain especially the frontal cortex.

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