Displaying publications 1 - 20 of 22 in total

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  1. Muthuraju, S., Abdullah, J.M.
    Orient Neuron Nexus, 2011;2(1):10-14.
    MyJurnal
    Neuronal cell death results from various circumstances such as hypoxia, ischemic and neurodegenerative diseases (NDs). In these events, the resulting modification of neurotransmitters, either excitatory or inhibitory, mediate much of the neuronal damage. However, this consequence depends upon their pre and post synaptic receptor activities which are the key mechanism for signal regulation. Among these, acetylcholine (ACh) is a well known neurotransmitter which is predominantly involved in neuroprotection as well as cognitive functions through its receptors activity, particularly the nicotinic subtypes. Several lines of evidence suggest that among these subtypes, a7 nicotinic acetylcholine receptor (a7nAChR) offers much promise for neuroprotective role in relation to the central nervous system (CNS) disorders like schizophrenia and Alzheimer's disease (AD). Several lines of evidence exist to show the potential mechanisms in which this nAChR subtype and its agonists such as nicotine, that trigger the a7nAChR-mediated suppression of neuronal cell death. This review focuses on the potential role of a7nAChR in neuroprotection by examining recent experimental data, both in vitro and in vivo, that argue for the neuroprotective role of a7nAChR in the CNS.
  2. Islam, M.R., Muthuraju, S., Tarmizi, C.H., Zulkifli, M.M., Osman, H., Mohamad, H., et al.
    ASM Science Journal, 2012;6(2):95-102.
    MyJurnal
    Epilepsy is a neurological disorder characterized by recurrent seizures resulting from excessive abnormal electrical discharges in the brain. Medicinal plants may play an invaluable role to discover the new antiepileptic drugs. The aim of the present study was to investigate the anticonvulsant activity of α-terpineol isolated from Myristica fragrans Hountt. The α-terpineol showed a significant inhibition of the seizure episodes and spikes in absence seizures model of Genetic Absence Epilepsy Rats from Strasbourg (GAERS) rats by using electroencephalography records. It showed dose-dependent anticonvulsant activity that was comparable to the known antiepileptic drug of diazepam. It showed a rapid onset and relatively short duration of anticonvulsant effects. The present findings suggest that α-terpineol might possess antiepileptic activities against the partial seizures of human because it prevented seizures in well-established genetic absence seizure animal model of GAERS rats.
  3. Muthuraju S, Pati S, Rafiqul M, Abdullah JM, Jaafar H
    J Biosci, 2013 Mar;38(1):93-103.
    PMID: 23385817
    Traumatic brain injury (TBI) causes significant mortality in most developing countries worldwide. At present, it is imperative to identify a treatment to address the devastating post-TBI consequences. Therefore, the present study has been performed to assess the specific effect of immediate exposure to normabaric hyperoxia (NBO) after fluid percussion injury (FPI) in the striatum of mice. To execute FPI, mice were anesthetised and sorted into (i) a TBI group, (ii) a sham group without injury and (iii) a TBI group treated with immediate exposure to NBO for 3 h. Afterwards, brains were harvested for morphological assessment. The results revealed no changes in morphological and neuronal damage in the sham group as compared to the TBI group. Conversely, the TBI group showed severe morphological changes as well as neuronal damage as compared to the TBI group exposed to NBO for 3 h. Interestingly, our findings also suggested that NBO treatment could diminish the neuronal damage in the striatum of mice after FPI. Neuronal damage was evaluated at different points of injury and the neighbouring areas using morphology, neuronal apoptotic cell death and pan-neuronal markers to determine the complete neuronal structure. In conclusion, immediate exposure to NBO following FPI could be a potential therapeutic approach to reduce neuronal damage in the TBI model.
  4. Al-Rahbi B, Zakaria R, Muthuraju S, Othman Z, Hassan A
    Malays J Med Sci, 2013 Mar;20(2):35-40.
    PMID: 23983575 MyJurnal
    Depression is one of the common post-menopausal symptoms. In addition to estrogen deficiency, social instability stress may contribute as an additional underlying factor in the development of depressive behaviour in females. Therefore, this study was aimed at examining the influence of social instability stress on depressive behaviour in ovariectomized rats.
  5. Muthuraju S, Islam MR, Pati S, Jaafar H, Abdullah JM, Yusoff KM
    Int J Neurosci, 2015;125(9):686-92.
    PMID: 25180987 DOI: 10.3109/00207454.2014.961065
    Dopamine (DA) is one of the key neurotransmitters in the striatum, which is functionally important for a variety of cognitive and motor behaviours. It is known that the striatum is vulnerable to damage from traumatic brain injury (TBI). However, a therapeutic approach has not yet been established to treat TBI. Hence, the present work aimed to evaluate the ability of Normobaric hyperoxia treatment (NBOT) to recover dopaminergic neurons following a fluid percussion injury (FPI) as a TBI experimental animal model. To examine this, mice were divided into four groups: (i) Control, (ii) Sham, (iii) FPI and (iv) FPI+NBOT. Mice were anesthetized and surgically prepared for FPI in the striatum and immediate exposure to NBOT at various time points (3, 6, 12 and 24 h). Dopamine levels were then estimated post injury by utilizing a commercially available ELISA method specific to DA. We found that DA levels were significantly reduced at 3 h, but there was no reduction at 6, 12 and 24 h in FPI groups when compared to the control and sham groups. Subjects receiving NBOT showed consistent increased DA levels at each time point when compared with Sham and FPI groups. These results suggest that FPI may alter DA levels at the early post-TBI stages but not in later stages. While DA levels increased in 6, 12 and 24 h in the FPI groups, NBOT could be used to accelerate the prevention of early dopaminergic neuronal damage following FPI injury and improve DA levels consistently.
  6. Muthuraju S, Taha S, Pati S, Rafique M, Jaafar H, Abdullah JM
    Int J Biomed Sci, 2013 Dec;9(4):194-204.
    PMID: 24711754
    Closed traumatic brain injury (CTBI) leads to increase mortality rates in developing countries. However, a sustainable therapeutic approach has not been established yet. Therefore, the present study was designed to evaluate the impact of normabaric hyperoxia treatment (NBOT) on striatum associated Locomotor Activity (LA) in IntelliCage after Fluid-Percussion Injury (FPI). Animals were divided in four groups: Group I control (n=24), Group II sham (n=24), Group III FPI (n=24) and Group IV FPI with NBOT (n=24). Animals were habituated in IntelliCage for 4 days following transponder implanted in mice neck region on day 5. Then the LA of all groups was assessed 6hr daily for 5 days before inducing FPI. On day 6, cannula was implanted on the striatum, on day 7 FPI was performed in Group III (kept in normal environment) and IV (immediately exposed to NBOT for 3 hr). LA (in terms of number of visits in all four corners) was assessed 6 hr at days 1, 7, 14, 21 and 28 following FPI. After the animals were sacrificed to study the neuronal damage, dopamine receptors and transporters expression in striatum. The results suggested that the LA of FPI impaired mice as compared to the control and sham showed less number of visits in all four corners in IntelliCage. Morphological results revealed that FPI induced neuronal damage as compared to sham and control. Dopamine receptors and transporters were down regulated in the FPI group as compared to the control. Immediate exposure to NBOT improved LA in terms of increased number of visits in all four corners, reduced number of cell death and improved receptor expression as compared to FPI. In conclusion, NBOT exposure could improve the LA of mice following FPI through prevention of neuronal damage, improved dopamine receptors and transporters.
  7. Al-Rahbi B, Zakaria R, Othman Z, Hassan A, Muthuraju S, Wan Mohammad WM
    Biomed Res Int, 2013;2013:493643.
    PMID: 23841073 DOI: 10.1155/2013/493643
    This study aims to compare the effects of social instability stress on memory and anxiety- and depressive-like behaviour between sham-operated controls and ovariectomised (OVX) rats. Forty adult female Sprague-Dawley rats (8 weeks old) were randomly divided into four groups, (n = 10 per group). These were non-stressed sham-operated control rats, stressed sham-operated control rats, non-stressed OVX rats, and stressed OVX rats. The rats were subjected to social instability stress procedure for 15 days. Novel object recognition, open field, and forced swim tests were conducted after the stress procedure. Serum estradiol, ACTH and corticosterone levels were measured using commercially available ELISA kits. Lower serum estradiol level and uterine weight with higher weight gain were observed in OVX rats compared to sham-operated controls. Serum ACTH, and corticosterone levels were higher in stressed compared to non-stressed groups. Memory deficit and anxiety- and depressive-like behaviour were significantly increased in stressed compared to non-stressed OVX rats but these changes were not seen in sham-operated controls. These results suggest that the high circulating corticosterone acts synergistically with low circulating estradiol to exert negative effects on mood and memory function.
  8. Pati S, Muthuraju S, Hadi RA, Huat TJ, Singh S, Maletic-Savatic M, et al.
    Curr Stem Cell Res Ther, 2016;11(2):149-57.
    PMID: 26763886
    Traumatic brain injury (TBI) imposes horrendous neurophysiological alterations leading to most devastating forms of neuro-disability. Which includes impaired cognition, distorted locomotors activity and psychosomatic disability in both youths and adults. Emerging evidence from recent studies has identified mesenchymal stem cells (MSCs) as one of the promising category of stem cells having excellent neuroregenerative capability in TBI victims. Some of the clinical and animal studies reported that MSCs transplantation could cure neuronal damage as well as improve cognitive and locomotors behaviors in TBI. However, mechanism behind their broad spectrum neuroregenerative potential in TBI has not been reviewed yet. Therefore, in the present article, we present a comprehensive data on the important attributes of MSCs, such as neurotransdifferentiation, neuroprotection, axonal repair and plasticity, maintenance of blood-brain integrity, reduction of reactive oxygen species (ROS) and immunomodulation. We have reviewed in detail the crucial neurogenic capabilities of MSCs in vivo and provided consolidated knowledge regarding their cellular remodeling in TBI for future therapeutic implications.
  9. Al-Rahbi B, Zakaria R, Othman Z, Hassan A, Mohd Ismail ZI, Muthuraju S
    Acta Histochem, 2014 Jan;116(1):79-88.
    PMID: 23810156 DOI: 10.1016/j.acthis.2013.05.004
    Recently, our research team has reported that Tualang honey was able to improve immediate memory in postmenopausal women comparable with that of estrogen progestin therapy. Therefore the aim of the present study was to examine the effects of Tualang honey supplement on hippocampal morphology and memory performance in ovariectomized (OVX) rats exposed to social instability stress. Female Sprague-Dawley rats were divided into six groups: (i) sham-operated controls, (ii) stressed sham-operated controls, (iii) OVX rats, (iv) stressed OVX rats, (v) stressed OVX rats treated with 17β-estradiol (E2), and (vi) stressed OVX rats treated with Tualang honey. These rats were subjected to social instability stress procedure followed by novel object recognition (NOR) test. Right brain hemispheres were subjected to Nissl staining. The number and arrangement of pyramidal neurons in regions of CA1, CA2, CA3 and the dentate gyrus (DG) were recorded. Two-way ANOVA analyses showed significant interactions between stress and OVX in both STM and LTM test as well as number of Nissl-positive cells in all hippocampal regions. Both E2 and Tualang honey treatments improved both short-term and long-term memory and enhanced the neuronal proliferation of hippocampal CA2, CA3 and DG regions compared to that of untreated stressed OVX rats.
  10. Abdo Qaid EY, Zulkipli NN, Zakaria R, Ahmad AH, Othman Z, Muthuraju S, et al.
    Int J Neurosci, 2021 May;131(5):482-488.
    PMID: 32202188 DOI: 10.1080/00207454.2020.1746308
    Hypoxia has been associated with cognitive impairment. Many studies have investigated the role of mTOR signalling pathway in cognitive functions but its role in hypoxia-induced cognitive impairment remains controversial. This review aimed to elucidate the role of mTOR in the mechanisms of cognitive impairment that may pave the way towards the mechanistic understanding and therapeutic intervention of hypoxia-induced cognitive impairment. mTORC1 is normally regulated during mild or acute hypoxic exposure giving rise to neuroprotection, whereas it is overactivated during severe or chronic hypoxia giving rise to neuronal cells death. Thus, it is worth exploring the possibility of maintaining normal mTORC1 activity and thereby preventing cognitive impairment during severe or chronic hypoxia.
  11. Nor Nazli NA, Muthuraju S, Ahmad F, Mohamed Yusoff AA, Jaafar H, Shamsuddin S, et al.
    Malays J Med Sci, 2023 Feb;30(1):92-106.
    PMID: 36875187 DOI: 10.21315/mjms2023.30.1.8
    BACKGROUND: The present study aimed to understand the characterisation of human hippocampal astrocyte following hypoxia exposure. Based on the preliminary screening, 15 min was chosen as the time point and the cells were exposed to different oxygen percentages.

    METHODS: The Trypan blue viability assay used to examine cell death. Immunofluorescence assay, glial fibrillary acidic protein (GFAP) was used to portray the morphology of astrocytes. The hypoxia-inducible factor 1 (HIF-1) staining was performed to confirm hypoxia induced cell death and there was a dramatic expression of HIF-1α displayed in exposed astrocyte cells compared to the control. In molecular level, genes were chosen, such as glyceraldehyde 3-phosphate dehydrogenase (GAPDH), GFAP, HIF-1α and B-cell lymphoma 2 (Bcl-2) and ran the reverse transcription-polymerase chain reaction (RT-PCR).

    RESULTS: Microscope revealed a filamentous and clear nucleus appearance in a control whereas the rupture nuclei with no rigid structure of the cell were found in the 3% oxygen. The control and hypoxia cells were also stained with the annexin V-fluorescein isothiocyanate (annexin V-FITC). Fluorescence microscope reveals astrocyte cells after hypoxia showed higher expression of nuclei but not in control. Merging PI and FITC showed the differences of nuclei expression between the control and hypoxia. In the molecular analysis, there were significant changes of GFAP, HIF-1α and Bcl-2 in hypoxia exposed cells when compared to the control group.

    CONCLUSION: Cells that were exposed to hypoxia (3% oxygen for 15 min) clearly showed damage. General view of human hippocampal astrocyte genomic response to hypoxia was obtained.

  12. Pati S, Supeno NE, Muthuraju S, Abdul Hadi R, Ghani AR, Idris FM, et al.
    Biomed Res Int, 2014;2014:503162.
    PMID: 25254208 DOI: 10.1155/2014/503162
    The striatum is considered to be the central processing unit of the basal ganglia in locomotor activity and cognitive function of the brain. IGF-1 could act as a control switch for the long-term proliferation and survival of EGF+bFGF-responsive cultured embryonic striatal stem cell (ESSC), while LIF imposes a negative impact on cell proliferation. The IGF-1-treated ESSCs also showed elevated hTERT expression with demonstration of self-renewal and trilineage commitment (astrocytes, oligodendrocytes, and neurons). In order to decipher the underlying regulatory microRNA (miRNA)s in IGF-1/LIF-treated ESSC-derived neurogenesis, we performed in-depth miRNA profiling at 12 days in vitro and analyzed the candidates using the Partek Genome Suite software. The annotated miRNA fingerprints delineated the differential expressions of miR-143, miR-433, and miR-503 specific to IGF-1 treatment. Similarly, the LIF-treated ESSCs demonstrated specific expression of miR-326, miR-181, and miR-22, as they were nonsignificant in IGF-treated ESSCs. To elucidate the possible downstream pathways, we performed in silico mapping of the said miRNAs into ingenuity pathway analysis. Our findings revealed the important mRNA targets of the miRNAs and suggested specific interactomes. The above studies introduced a new genre of miRNAs for ESSC-based neuroregenerative therapeutic applications.
  13. Tijjani Salihu A, Muthuraju S, Aziz Mohamed Yusoff A, Ahmad F, Zulkifli Mustafa M, Jaafar H, et al.
    Behav Brain Res, 2016 10 01;312:374-84.
    PMID: 27327104 DOI: 10.1016/j.bbr.2016.06.034
    The present study aimed to investigate the behavior and neuronal morphological changes in the perihaemorrhagic tissue of the mouse intracerebellar haemorrhage experimental model. Adult male Swiss albino mice were stereotactically infused with collagenase type VII (0.4U/μl of saline) unilaterally in to the cerebellum, following anaesthesia. Motor deficits were assessed using open field and composite score for evaluating the mouse model of cerebellar ataxia at 1, 3, 7, 14 and 21 days after collagenase infusion. The animals were sacrificed at the same time interval for evaluation of perihaematomal neuronal degeneration using haematoxylin and eosin staining and Annexin V-FITC/Propidium iodide assay. At the end of the study, it was found that infusion of 0.4U collagenase produces significant locomotor and ataxic deficit in the mice especially within the first week post surgery, and that this gradually improved within three weeks. Neuronal degeneration evident by cytoplasmic shrinkage and nuclear pyknosis was observed at the perihaematomal area after one day; especially at 3 and 7 days post haemorrhage. By 21 days, both the haematoma and degenerating neurons in the perihaematomal area were phagocytosed and the remaining neuronal cells around the scar tissue appeared normal. Moreover, Annexin-V/propidium iodide-positive cells were observed at the perihaematomal area at 3 and 7 days implying that the neurons likely die via apoptosis. It was concluded that a population of potentially salvageable neurons exist in the perihaematomal area after cerebellar haemorrhage throughout a wide time window that could be amenable to treatment.
  14. Qaid EYA, Zakaria R, Mohd Yusof NA, Sulaiman SF, Shafin N, Othman Z, et al.
    Turk J Pharm Sci, 2020 Oct;17(5):555-564.
    PMID: 33177938 DOI: 10.4274/tjps.galenos.2019.32704
    Objectives: A growing body of evidence indicates that hypoxia exposure causes learning and memory deficits. An effective natural therapeutic approach has, however, not been explored widely. Our previous studies found that Tualang honey administration protected learning and memory functions in ovariectomized rats. Therefore, the present study investigated its efficacy in ameliorating hypoxia-induced memory deficits in adult male Sprague Dawley rats.

    Materials and Methods: The rats were divided into four groups: i) Normoxia treated with sucrose (n=12), ii) Normoxia treated with Tualang honey (n=12), iii) Hypoxia treated with sucrose (n=12), and iv) Hypoxia treated with Tualang honey (n=12). Tualang honey (0.2 g/kg/BW) and sucrose (1 mL of 7.9%) supplementations were administered orally to the rats daily for 14 days. Then the hypoxia groups were exposed to hypoxia (~11%) for 7 days, while the normoxia groups were kept in normal conditions. Following exposure to hypoxia, the rats' memories were analyzed using a novel object recognition task and T-maze test.

    Results: The data revealed that rats exposed to hypoxia showed significant impairment in short-term memory (STM), spatial memory (p<0.01), and long-term memory (LTM) when compared to the normoxia group. Hypoxia rats treated with Tualang honey showed significant improvement in STM, LTM, and spatial memory (p<0.05) compared with those treated with sucrose (p<0.05). Tualang honey also reduced neuronal damage in the hippocampus of adult male Sprague Dawley rats exposed to hypoxia.

    Conclusion: It is suggested that Tualang honey pretreatment has protective effects against hypoxia-induced memory deficits, possibly through its antioxidant contents.

  15. Chuang HG, Aziz NHA, Wong JH, Mustapha M, Abdullah JM, Idris Z, et al.
    Eur Neuropsychopharmacol, 2021 04;45:59-72.
    PMID: 32014377 DOI: 10.1016/j.euroneuro.2019.12.121
    The present study focused on investigating the effect of toll-like receptor 4 (TLR4) antagonist Lipopolysaccharide-Rhodobacter sphaeroides(LPS-RS) on acute, stress-induced voluntary ethanol preference and drinking behaviour, neuronal components activation, and gene expression associated with stress and addictive behaviour. This study involved the exposure of restraint stress and social isolation using Swiss Albino mice. Two-bottle choice ethanol preference analysis was used in the evaluation of voluntary ethanol seeking and drinking behaviour. Several behavioural assessments were carried out to assess fear and anxiety-like behaviour, neuromuscular ability, motor coordination and locomotion. Morphological and immunoreactivity analysis and gene expression analysis were done after the completion of behavioural assessments. TLR4 antagonist LPS-RS treated stressed-mice showed a significant decrease in ethanol drinking compared with stressed mice. Behavioural results showed that stress exposure induced fear and anxiety-like behaviour; however; no significant deficit was found on motor coordination, neuromuscular ability, locomotion and exploratory behaviour among groups. Morphological analysis showed no significant change in the prefrontal cortex and hippocampus among all groups, while immunoreactivity analysis showed higher expression of c-Fos in prefrontal cortex and hippocampus, higher TLR4 expression in the prefrontal cortex and glial fibrillary acidic protein (GFAP) in hippocampus among stressed-animals. Stressed-mice also showed significant increase in TLR4, Nuclear Factor-Kappa B (NF-kB), inducible nitric oxide synthase (iNOS), dopamine receptor D2 (DRD2), cyclic adenosine monophosphate (cAMP) response element binding protein-1 (CREB-1) and opioid receptor MU-1 (OPRM-1) genes expression compared with control and LPS-RS treated stressed-mice. As a conclusion, the antagonism of TLR4 could provide therapeutic value in the treatment of stress-induced addiction.
  16. Binti Mohd Yusuf Yeo NA, Muthuraju S, Wong JH, Mohammed FR, Senik MH, Zhang J, et al.
    Brain Behav, 2018 09;8(9):e01093.
    PMID: 30105867 DOI: 10.1002/brb3.1093
    INTRODUCTION: Centella asiatica is an herbal plant that contains phytochemicals that are widely believed to have positive effects on cognitive function. The adolescent stage is a critical development period for the maturation of brain processes that encompass changes in physical and psychological systems. However, the effect of C. asiatica has not been extensively studied in adolescents. The aim of this study was therefore to investigate the effects of a C. asiatica extract on the enhancement of learning and memory in adolescent rats.

    METHODS: The locomotor activity, learning, and memory were assessed by using open field test and water T-maze test. This study also examined changes in neuronal cell morphology using cresyl violet and apoptosis staining. We also performed immunohistochemical study to analyse the expression of the glutamate AMPA receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) GluA1 subunit and the GABA receptor (γ-Aminobutyric Acid) subtype GABAA α1 subunit in the hippocampus of the same animals.

    RESULTS: We found no significant changes in locomotor activity (p > 0.05). The water T-maze data showed that 30 mg/kg dose significantly (p  0.05). Histological data revealed no neuronal morphological changes. Immunohistochemical analysis revealed increased expression of the AMPA GluA1 receptor subunit but there was no effect on GABAA receptor α1 subunit expression in the CA1 and CA2 subregions of the hippocampus.

    CONCLUSIONS: The C. asiatica extract therefore improved hippocampus-dependent spatial learning and memory in a dose-dependent manner in rats through the GluA1-containing AMPA receptor in the CA1 and CA2 sub regions of the hippocampus.

  17. Wong JH, Reza F, Muthuraju S, Chuang HG, Zhang J, Senik MH, et al.
    J Integr Neurosci, 2020 Jun 30;19(2):217-227.
    PMID: 32706186 DOI: 10.31083/j.jin.2020.02.50
    Centella asiatica is notable for its wide range of biological activities beneficial to human health, particularly its cognitive enhancement and neuroprotective effects. The α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors are ionotropic glutamate receptors mediating fast excitatory neurotransmission essential in long-term potentiation widely thought to be the cellular mechanism of learning and memory. The method of whole-cell patch-clamp was used to study the effect of the acute application of Centella asiatica extract on the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated spontaneous excitatory postsynaptic currents in the entorhinal cortex of rat brain slices. The respective low dose of test compounds significantly increased the amplitude of spontaneous excitatory postsynaptic currents while having no significant effects on the frequency. The findings suggested that Centella asiatica extract increased the response of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors at the postsynaptic level, revealing the potential role of Centella asiatica in modulating the glutamatergic responses in the entorhinal cortex of rat brain slices to produce cognitive enhancement effects.
  18. Iman IN, Yusof NAM, Talib UN, Ahmad NAZ, Norazit A, Kumar J, et al.
    Front Behav Neurosci, 2021;15:683780.
    PMID: 34149373 DOI: 10.3389/fnbeh.2021.683780
    The use of animal models for substance use disorder (SUD) has made an important contribution in the investigation of the behavioral and molecular mechanisms underlying substance abuse and addiction. Here, we review a novel and comprehensive behavioral platform to characterize addiction-like traits in rodents using a fully automated learning system, the IntelliCage. This system simultaneously captures the basic behavioral navigation, reward preference, and aversion, as well as the multi-dimensional complex behaviors and cognitive functions of group-housed rodents. It can reliably capture and track locomotor and cognitive pattern alterations associated with the development of substance addiction. Thus, the IntelliCage learning system offers a potentially efficient, flexible, and sensitive tool for the high-throughput screening of the rodent SUD model.
  19. Abg Abd Wahab DY, Gau CH, Zakaria R, Muthu Karuppan MK, A-Rahbi BS, Abdullah Z, et al.
    Biomed Res Int, 2019;2019:1767203.
    PMID: 31815123 DOI: 10.1155/2019/1767203
    Neurological diseases particularly Alzheimer's disease (AD), Parkinson's disease (PD), stroke, and epilepsy are on the rise all around the world causing morbidity and mortality globally with a common symptom of gradual loss or impairment of motor behaviour. Striatum, which is a component of the basal ganglia, is involved in facilitating voluntary movement while the cerebellum is involved in the maintenance of balance and coordination of voluntary movements. Dopamine, serotonin, gamma-aminobutyric acid (GABA), and glutamate, to name a few, interact in regulating the excitation and inhibition of motor neurons. In another hand, interestingly, the motor loss associated with neurological diseases is possibly resulted from neuroinflammation induced by the neuroimmune system. Toll-like receptors (TLRs) are present in the central nervous system (CNS), specifically and primarily expressed in microglia and are also found on neurons and astrocytes, functioning mainly in the regulation of proinflammatory cytokine production. TLRs are always found to be associated or involved in the induction of neuroinflammation in neurodegenerative diseases. Activation of toll-like receptor 4 (TLR4) through TLR4 agonist, lipopolysaccharide (LPS), stimulation initiate a signaling cascade whereby the TLR4-LPS interaction has been found to result in physiological and behavioural changes including retardation of motor activity in the mouse model. TLR4 inhibitor TAK-242 was reflected in the reduction of the spinal cord pathology along with the motor improvement in ALS mouse. There is cross talk with neuroinflammation and neurochemicals. For example, TLR4 activation by LPS is noted to release proinflammatory cytokines, IL-1β, from microglia that subsequently suppresses GABA receptor activities at the postsynaptic site and reduces GABA synthesis at the presynaptic site. Glial glutamate transporter activities are also found to be suppressed, showing the association between TLR4 activation and the related neurotransmitters and corresponding receptors and transporters in the event of neuroinflammation. This review is helpful to understand the connection between neurotransmitter and neuroinflammation in striatum- and cerebellum-mediated motor behaviour.
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