Displaying publications 1 - 20 of 109 in total

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  1. α6-Containing GABAA Receptors: Functional Roles and Therapeutic Potentials
    Sieghart W, Chiou LC, Ernst M, Fabjan J, M Savić M, Lee MT
    Pharmacol Rev, 2022 Jan;74(1):238-270.
    PMID: 35017178 DOI: 10.1124/pharmrev.121.000293
    GABAA receptors containing the α6 subunit are highly expressed in cerebellar granule cells and less abundantly in many other neuronal and peripheral tissues. Here, we for the first time summarize their importance for the functions of the cerebellum and the nervous system. The cerebellum is not only involved in motor control but also in cognitive, emotional, and social behaviors. α6βγ2 GABAA receptors located at cerebellar Golgi cell/granule cell synapses enhance the precision of inputs required for cerebellar timing of motor activity and are thus involved in cognitive processing and adequate responses to our environment. Extrasynaptic α6βδ GABAA receptors regulate the amount of information entering the cerebellum by their tonic inhibition of granule cells, and their optimal functioning enhances input filtering or contrast. The complex roles of the cerebellum in multiple brain functions can be compromised by genetic or neurodevelopmental causes that lead to a hypofunction of cerebellar α6-containing GABAA receptors. Animal models mimicking neuropsychiatric phenotypes suggest that compounds selectively activating or positively modulating cerebellar α6-containing GABAA receptors can alleviate essential tremor and motor disturbances in Angelman and Down syndrome as well as impaired prepulse inhibition in neuropsychiatric disorders and reduce migraine and trigeminal-related pain via α6-containing GABAA receptors in trigeminal ganglia. Genetic studies in humans suggest an association of the human GABAA receptor α6 subunit gene with stress-associated disorders. Animal studies support this conclusion. Neuroimaging and post-mortem studies in humans further support an involvement of α6-containing GABAA receptors in various neuropsychiatric disorders, pointing to a broad therapeutic potential of drugs modulating α6-containing GABAA receptors. SIGNIFICANCE STATEMENT: α6-Containing GABAA receptors are abundantly expressed in cerebellar granule cells, but their pathophysiological roles are widely unknown, and they are thus out of the mainstream of GABAA receptor research. Anatomical and electrophysiological evidence indicates that these receptors have a crucial function in neuronal circuits of the cerebellum and the nervous system, and experimental, genetic, post-mortem, and pharmacological studies indicate that selective modulation of these receptors offers therapeutic prospects for a variety of neuropsychiatric disorders and for stress and its consequences.
    Matched MeSH terms: Neurons/metabolism
  2. Current Perspectives of Healthy Mitochondrial Function for Healthy Neurons
    Arunachalam M, Ramesh M, Thiagarajan V, Singla SK, Mudhol S, Muthukumar SP
    Curr Drug Targets, 2021;22(14):1688-1703.
    PMID: 33618645 DOI: 10.2174/1389450122666210222163528
    The neuron is high-energy utilizing tissue. The rate of neuronal cell respiration is higher than in other cells. Cellular respiration occurs with mitochondria. The healthy production and functions of mitochondria play a key role in the maintenance of healthy neurons. In pathological conditions such as neurodegenerative diseases, healthy mitochondria help to alleviate pathological events in neuronal cells. Conversely, mitochondrial dysfunction promotes the acceleration of the neurodegenerative process. Furthermore, glial-derived mitochondria contribute to multiple roles in the regulation of healthy neuron functions. It also supports releasing of the neurotransmitters; generation of the impulses, regulation of the membrane potential and molecular dynamics; controlling of the axonal transport; controlling of the mitochondrial fission and fusion functions in the peripheral as well as the central nervous system. Moreover, it plays a key role in the regeneration process of neuronal cells. Therefore, healthy mitochondria can provide a healthy environment for neuronal cell function and can treat neurodegenerative disorders. In this review, we explore the current view of healthy mitochondria and their role in healthy neuronal functions.
    Matched MeSH terms: Neurons/metabolism
  3. Fulltext Single-cell RNA sequencing analysis of human Alzheimer's disease brain samples reveals neuronal and glial specific cells differential expression
    Soreq L, Bird H, Mohamed W, Hardy J
    PLoS One, 2023;18(2):e0277630.
    PMID: 36827281 DOI: 10.1371/journal.pone.0277630
    Alzheimer's disease is the most common neurological disease worldwide. Unfortunately, there are currently no effective treatment methods nor early detection methods. Furthermore, the disease underlying molecular mechanisms are poorly understood. Global bulk gene expression profiling suggested that the disease is governed by diverse transcriptional regulatory networks. Thus, to identify distinct transcriptional networks impacted into distinct neuronal populations in Alzheimer, we surveyed gene expression differences in over 25,000 single-nuclei collected from the brains of two Alzheimer's in disease patients in Braak stage I and II and age- and gender-matched controls hippocampal brain samples. APOE status was not measured for this study samples (as well as CERAD and THAL scores). Our bioinformatic analysis identified discrete glial, immune, neuronal and vascular cell populations spanning Alzheimer's disease and controls. Astrocytes and microglia displayed the greatest transcriptomic impacts, with the induction of both shared and distinct gene programs.
    Matched MeSH terms: Neurons/metabolism
  4. Dysregulation of the orexinergic system: A potential neuropeptide target in depression
    Khairuddin S, Aquili L, Heng BC, Hoo TLC, Wong KH, Lim LW
    Neurosci Biobehav Rev, 2020 11;118:384-396.
    PMID: 32768489 DOI: 10.1016/j.neubiorev.2020.07.040
    Orexins are highly involved in regulating the circadian rhythm, the brain's reward mechanism, and the neuroendocrine response to stress. The disruption of orexin regulation is known to be associated with depression. Preclinical studies in rodents have identified the dorsomedial/perifornical and lateral areas of the hypothalamus as the population of orexinergic neurons that are primarily responsible for mediating depression-induced neuroanatomical changes in the brain. There is still no consensus regarding whether hyperactivity or hypoactivity of orexin signaling is responsible for producing depressive-like behaviour. Likewise, clinical studies indicated a general disruption in orexin signaling in depressive patients, but did not report definitive evidence of either hyperactivity or hypoactivity. Nevertheless, given the various reciprocal connections between orexin neurons and multiple brain regions, it is plausible that this involves a differential signaling network with orexin neurons as the coordination center. Here, an overview of preclinical and clinical evidence is provided as a basis for understanding the consequences of altered orexin signaling on neural circuitries modulating different aspects of the physiopathology of depression.
    Matched MeSH terms: Neurons/metabolism
  5. Kisspeptin-10 Mitigates α-Synuclein-Mediated Mitochondrial Apoptosis in SH-SY5Y-Derived Neurons via a Kisspeptin Receptor-Independent Manner
    Simon C, Soga T, Parhar I
    Int J Mol Sci, 2023 Mar 23;24(7).
    PMID: 37047030 DOI: 10.3390/ijms24076056
    The hypothalamic neurohormone kisspeptin-10 (KP-10) was inherently implicated in cholinergic pathologies when aberrant fluctuations of expression patterns and receptor densities were discerned in neurodegenerative micromilieus. That said, despite variable degrees of functional redundancy, KP-10, which is biologically governed by its cognate G-protein-coupled receptor, GPR54, attenuated the progressive demise of α-synuclein (α-syn)-rich cholinergic-like neurons. Under explicitly modeled environments, in silico algorithms further rationalized the surface complementarities between KP-10 and α-syn when KP-10 was unambiguously accommodated in the C-terminal binding pockets of α-syn. Indeed, the neuroprotective relevance of KP-10's binding mechanisms can be insinuated in the amelioration of α-syn-mediated neurotoxicity; yet it is obscure whether these extenuative circumstances are contingent upon prior GPR54 activation. Herein, choline acetyltransferase (ChAT)-positive SH-SY5Y neurons were engineered ad hoc to transiently overexpress human wild-type or E46K mutant α-syn while the mitigation of α-syn-induced neuronal death was ascertained via flow cytometric and immunocytochemical quantification. Recapitulating the specificity observed on cell viability, exogenously administered KP-10 (0.1 µM) substantially suppressed wild-type and E46K mutant α-syn-mediated apoptosis and mitochondrial depolarization in cholinergic differentiated neurons. In particular, co-administrations with a GPR54 antagonist, kisspeptin-234 (KP-234), failed to abrogate the robust neuroprotection elicited by KP-10, thereby signifying a GPR54 dispensable mechanism of action. Consistent with these observations, KP-10 treatment further diminished α-syn and ChAT immunoreactivity in neurons overexpressing wild-type and E46K mutant α-syn. Overall, these findings lend additional credence to the previous notion that KP-10's binding zone may harness efficacious moieties of neuroprotective intent.
    Matched MeSH terms: Neurons/metabolism
  6. Fulltext REST Targets JAK-STAT and HIF-1 Signaling Pathways in Human Down Syndrome Brain and Neural Cells
    Huang T, Fakurazi S, Cheah PS, Ling KH
    Int J Mol Sci, 2023 Jun 10;24(12).
    PMID: 37373133 DOI: 10.3390/ijms24129980
    Down syndrome (DS) is the most frequently diagnosed chromosomal disorder of chromosome 21 (HSA21) aneuploidy, characterized by intellectual disability and reduced lifespan. The transcription repressor, Repressor Element-1 Silencing Transcription factor (REST), which acts as an epigenetic regulator, is a crucial regulator of neuronal and glial gene expression. In this study, we identified and investigated the role of REST-target genes in human brain tissues, cerebral organoids, and neural cells in Down syndrome. Gene expression datasets generated from healthy controls and DS samples of human brain tissues, cerebral organoids, NPC, neurons, and astrocytes were retrieved from the Gene Ontology (GEO) and Sequence Read Archive (SRA) databases. Differential expression analysis was performed on all datasets to produce differential expression genes (DEGs) between DS and control groups. REST-targeted DEGs were subjected to functional ontologies, pathways, and network analyses. We found that REST-targeted DEGs in DS were enriched for the JAK-STAT and HIF-1 signaling pathways across multiple distinct brain regions, ages, and neural cell types. We also identified REST-targeted DEGs involved in nervous system development, cell differentiation, fatty acid metabolism and inflammation in the DS brain. Based on the findings, we propose REST as the critical regulator and a promising therapeutic target to modulate homeostatic gene expression in the DS brain.
    Matched MeSH terms: Neurons/metabolism
  7. Fulltext TRPM4 blocking antibody reduces neuronal excitotoxicity by specifically inhibiting glutamate-induced calcium influx under chronic hypoxia
    Poore CP, Hazalin NAMN, Wei S, Low SW, Chen B, Nilius B, et al.
    Neurobiol Dis, 2024 Feb;191:106408.
    PMID: 38199274 DOI: 10.1016/j.nbd.2024.106408
    Excitotoxicity arises from unusually excessive activation of excitatory amino acid receptors such as glutamate receptors. Following an energy crisis, excitotoxicity is a major cause for neuronal death in neurological disorders. Many glutamate antagonists have been examined for their efficacy in mitigating excitotoxicity, but failed to generate beneficial outcome due to their side effects on healthy neurons where glutamate receptors are also blocked. In this study, we found that during chronic hypoxia there is upregulation and activation of a nonselective cation channel TRPM4 that contributes to the depolarized neuronal membrane potential and enhanced glutamate-induced calcium entry. TRPM4 is involved in modulating neuronal membrane excitability and calcium signaling, with a complex and multifaceted role in the brain. Here, we inhibited TRPM4 using a newly developed blocking antibody M4P, which could repolarize the resting membrane potential and ameliorate calcium influx upon glutamate stimulation. Importantly, M4P did not affect the functions of healthy neurons as the activity of TRPM4 channel is not upregulated under normoxia. Using a rat model of chronic hypoxia with both common carotid arteries occluded, we found that M4P treatment could reduce apoptosis in the neurons within the hippocampus, attenuate long-term potentiation impairment and improve the functions of learning and memory in this rat model. With specificity to hypoxic neurons, TRPM4 blocking antibody can be a novel way of controlling excitotoxicity with minimal side effects that are common among direct blockers of glutamate receptors.
    Matched MeSH terms: Neurons/metabolism
  8. RFamide peptides as mediators in environmental control of GnRH neurons
    Parhar I, Ogawa S, Kitahashi T
    Prog. Neurobiol., 2012 Aug;98(2):176-96.
    PMID: 22684005 DOI: 10.1016/j.pneurobio.2012.05.011
    Hypothalamic gonadotropin-releasing hormone (GnRH) is a key hormone for reproductive functions in vertebrates and non-vertebrates. Although GnRH neuronal system is regulated by several factors such as steroids, neurotransmitters and neuropeptides, it is not fully understood how environmental signals control the GnRH neuronal system. RFamide peptides, members of peptides possessing an Arg-Phe-NH(2) motif at their C-terminus, have recently been characterized as major regulators of GnRH neurons. In particular, two key RFamide peptides, kisspeptin and gonadotropin-inhibitory hormone (GnIH), are emerging as important regulators of the reproductive axis. Kisspeptin acts as the accelerator, directly driving GnRH neurons, whereas GnIH acts as the restraint. In addition, other RFamide peptides such as prolactin-releasing peptide (PrRP), PQRFa peptide, 26RFa/QRFP are also known to control reproduction. These RFamide peptides are regulated by environmental factors such as photoperiods, steroid hormones, metabolic signals, and stress. How environmental signals are integrated by RFamide peptides to regulate reproduction through the GnRH neurons?
    Matched MeSH terms: Neurons/metabolism*
  9. Unveiling the Role of Cytochrome P450 (2E1) in Human Brain Specifically in Parkinson's Disease - Literature Review
    Shah A, Ong CE, Pan Y
    Curr Drug Metab, 2021;22(9):698-708.
    PMID: 34325630 DOI: 10.2174/1389200222666210729115151
    BACKGROUND: In recent years, the significance of cytochrome P450 enzymes (CYPs) has expanded beyond their role in the liver. Factors such as genetics, environmental toxins, drug biotransformation and underlying diseases mediate the expression of these enzymes. Among the CYP enzymes, CYP2E1, a well-recognized monooxygenase enzyme involved in the metabolism of various endogenous and exogenous substances, plays a crucial role in the brain concerning the development of Parkinson's disease. The expression of CYP2E1 varies in different brain regions making certain regions more vulnerable than others. CYP2E1 expression is inducible which generates tissuedamaging radicals leading to oxidative stress, mitochondrial dysfunction and ultimately neurodegeneration.

    OBJECTIVE: Less is understood about the role of CYP2E1 in the central nervous system, therefore the purpose of the study was to investigate the relationship between the expression and activity of CYP2E1 enzyme relevant to Parkinson's disease and to identify whether an increase in the expression of CYP2E1 is associated with neurodegeneration.

    METHODS: The objectives of the study were achieved by implicating an unsystematic integrative literature review approach in which the literature was qualitatively analysed, critically evaluated and a new theory with an overall view of the mechanism was presented.

    RESULTS: The contribution of CYP2E1 in the development of Parkinson's disease was found to be significant as the negative effects of CYP2E1 overshadowed its protective detoxifying role.

    CONCLUSION: Overexpression of CYP2E1 seems detrimental to dopaminergic neurons, therefore, to overcome this, a synthetic biochemical is required, which paves the way for further research and development of valuable biomolecules.

    Matched MeSH terms: Dopaminergic Neurons/metabolism
  10. Gonadotropin-inhibitory hormone mediates behavioral stress responses
    Ubuka T, Parhar IS, Tsutsui K
    Gen Comp Endocrinol, 2018 09 01;265:202-206.
    PMID: 29510150 DOI: 10.1016/j.ygcen.2018.03.004
    Gonadotropin-inhibitory hormone (GnIH) is an inhibitor of the hypothalamic-pituitary-gonadal (HPG) axis. GnIH is also called RFamide-related peptide (RFRP) as GnIH peptides have a characteristic C-terminal LPXRFiamide (X = L or Q) sequence. GnIH is thought to be the mediator of stress by negatively regulating the HPG axis as various stressors increase GnIH mRNA, GnIH peptide or GnIH neuronal activity. On the other hand, GnIH may also mediate behavioral stress responses as GnIH neuronal fibers and GnIH receptors are widely located in the limbic system of telencephalon, diencephalon and midbrain area. Previous studies have shown that intracerebroventricular (i.c.v.) administration of GnIH (RFRP) blocks morphine-induced analgesia in hot plate and formalin injection tests in rats suggesting that GnIH increases sensitivity to pain. GnIH (RFRP) also increases anxiety-like behavior in rats. RNA interference of GnIH gene (GnIH RNAi) increases locomotor activity of white-crowned sparrow and Japanese quail and i.c.v. administration of GnIH decreases GnIH RNAi induced locomotor activity. It was further shown that i.c.v. administration of GnIH (RFRP) decreases aggressive behavior in male quail and sexual behavior in male rats, female white-crowned sparrow and female hamsters. These results suggest that GnIH decreases threat to homeostasis of the organism by increasing pain sensitivity, anxiety and decreasing locomotor activity, aggressive behavior and sexual behavior. GnIH may also mediate the effect of stress on behavior.
    Matched MeSH terms: Neurons/metabolism
  11. Alpha terpineol directs bone marrow mesenchymal stem cells toward neuronal lineage through regulation of wnt signaling pathway
    Ishaque A, Salim A, Simjee SU, Khan I, Adli DSH
    Cell Biochem Funct, 2023 Mar;41(2):223-233.
    PMID: 36651266 DOI: 10.1002/cbf.3775
    Central nervous system anomalies give rise to neuropathological consequences with immense damage to the neuronal tissues. Cell based therapeutics have the potential to manage several neuropathologies whereby the differentiated cells are explored for neuronal regeneration. The current study analyzes the effect of a bioactive compound, alpha terpineol (AT) on the differentiation of rat bone marrow derived mesenchymal stem cells (BM-MSCs) toward neuronal lineage, and explores regulation of differentiation process through the study of Wnt pathway mediators. BM-MSCs were cultured and characterized based on their surface markers and tri-lineage differentiation. Safe dose of AT as optimized by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium bromide assay, was used for the treatment of MSCs. Treated cells were analyzed for the neuronal, astroglial and germ layer transition markers at the gene and protein levels, by quantitative polymerase chain reaction and immunocytochemistry, respectively. Temporal expression of Wnt pathway genes was assessed during the course of neuronal differentiation. AT treated group showed significant upregulation of neuron specific (NSE, MAP2, Tau, Nestin, and NefL) and astroglial (GFAP) genes with positive expression of late neuronal markers. Germ layer transition analysis showed the overexpression of ectodermal markers (NCAM, Nestin, and Pax6), whereas endodermal (AFP, MixL1, and Sox17), and mesodermal (Mesp1 and T Brachyury) markers were also found to be upregulated. Wnt signaling pathway was activated during the initial phase (30 min) of differentiation, which later was downregulated at 1, 3, and 5 h. AT efficiently induces neuronal differentiation of BM-MSCs by regulating Wnt signaling. Overexpression of both early and late neuronal markers indicate their neuro-progenitor state and thus can be utilized as a promising approach in cellular therapeutics to treat various neurodegenerative ailments. In addition, exploration of the molecular pathways may be helpful to understand the mechanism of cell-based neuronal regeneration.
    Matched MeSH terms: Neurons/metabolism
  12. Fulltext Kisspeptin-1 regulates forebrain dopaminergic neurons in the zebrafish
    Abdul Satar NM, Ogawa S, Parhar IS
    Sci Rep, 2020 11 09;10(1):19361.
    PMID: 33168887 DOI: 10.1038/s41598-020-75777-0
    The habenula is a phylogenetically conserved epithalamic structure, which conveys negative information via inhibition of mesolimbic dopamine neurons. We have previously shown the expression of kisspeptin (Kiss1) in the habenula and its role in the modulation of fear responses in the zebrafish. In this study, to investigate whether habenular Kiss1 regulates fear responses via dopamine neurons in the zebrafish, Kiss1 peptides were intracranially administered close to the habenula, and the expression of dopamine-related genes (th1, th2 and dat) were examined in the brain using real-time PCR and dopamine levels using LC-MS/MS. th1 mRNA levels and dopamine levels were significantly increased in the telencephalon 24-h and 30-min after Kiss1 administration, respectively. In fish administered with Kiss1, expression of neural activity marker gene, npas4a and kiss1 gene were significantly decreased in the ventral habenula. Application of neural tracer into the median raphe, site of habenular Kiss1 neural terminal projections showed tracer-labelled projections in the medial forebrain bundle towards the telencephalon where dopamine neurons reside. These results suggest that Kiss1 negatively regulates its own neuronal activity in the ventral habenula via autocrine action. This, in turn affects neurons of the median raphe via interneurons, which project to the telencephalic dopaminergic neurons.
    Matched MeSH terms: Interneurons/metabolism; Neurons/metabolism; Dopaminergic Neurons/metabolism*
  13. Normobaric hyperoxia treatment prevents early alteration in dopamine level in mice striatum after fluid percussion injury: a biochemical approach
    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.
    Matched MeSH terms: Dopaminergic Neurons/metabolism*
  14. Fulltext GnRH neuron type-specific transcriptome analysis by laser captured single-cell microarray in the medaka
    Moriya S, Ogawa S, Parhar IS
    Biochem Biophys Res Commun, 2013 Jun 14;435(4):562-6.
    PMID: 23669040 DOI: 10.1016/j.bbrc.2013.05.004
    Most vertebrates possess at least two gonadotropin-releasing hormone (GnRH) neuron types. To understand the physiological significance of the multiple GnRH systems in the brain, we examined three GnRH neuron type-specific transcriptomes using single-cell microarray analyses in the medaka (Oryzias latipes). A microarray profile of the three GnRH neuron types revealed five genes that are uniquely expressed in specific GnRH neuron types. GnRH1 neurons expressed three genes that are homologous to functionally characterised genes, GnRH2 neurons uniquely expressed one unnamed gene, and GnRH3 neurons uniquely expressed one known gene. These genes may be involved in the modulation or maintenance of each GnRH neuron type.
    Matched MeSH terms: Neurons/metabolism*
  15. Fulltext Mathematical modeling of subthreshold resonant properties in pyloric dilator neurons
    Vazifehkhah Ghaffari B, Kouhnavard M, Aihara T, Kitajima T
    Biomed Res Int, 2015;2015:135787.
    PMID: 25960999 DOI: 10.1155/2015/135787
    Various types of neurons exhibit subthreshold resonance oscillation (preferred frequency response) to fluctuating sinusoidal input currents. This phenomenon is well known to influence the synaptic plasticity and frequency of neural network oscillation. This study evaluates the resonant properties of pacemaker pyloric dilator (PD) neurons in the central pattern generator network through mathematical modeling. From the pharmacological point of view, calcium currents cannot be blocked in PD neurons without removing the calcium-dependent potassium current. Thus, the effects of calcium (I(Ca)) and calcium-dependent potassium (I(KCa)) currents on resonant properties remain unclear. By taking advantage of Hodgkin-Huxley-type model of neuron and its equivalent RLC circuit, we examine the effects of changing resting membrane potential and those ionic currents on the resonance. Results show that changing the resting membrane potential influences the amplitude and frequency of resonance so that the strength of resonance (Q-value) increases by both depolarization and hyperpolarization of the resting membrane potential. Moreover, hyperpolarization-activated inward current (I(h)) and I(Ca) (in association with I(KCa)) are dominant factors on resonant properties at hyperpolarized and depolarized potentials, respectively. Through mathematical analysis, results indicate that I h and I(KCa) affect the resonant properties of PD neurons. However, I(Ca) only has an amplifying effect on the resonance amplitude of these neurons.
    Matched MeSH terms: Neurons/metabolism*
  16. Effects of glycyrrhizic acid and steroid treatment on corticotropin releasing factor and beta-endorphin containing neurons of the hypothalamus of the rat
    Ruszymah BH, Nabishah BM, Aminuddin S, Sarjit S, Khalid BA
    Malays J Pathol, 1999 Jun;21(1):51-8.
    PMID: 10879279
    Corticotrophin releasing factor (CRF) and beta-endorphin (beta EP) containing neurons are shown to be present in the hypothalamus and both neurons are found at the paraventricular nucleus (PVN). Steroid hormones have been found to alter the plasma level of these neurotransmitters. Glycyrrhizic acid (GCA) is the active component of liquorice. GCA inhibits the enzyme 11 beta-hydroxysteroid dehydrogenase (11HSD) which is needed for the inactivation of the steroid pathway, so therefore would cause changes to these neurons. The aim of this study was to investigate the effects of GCA as well as deoxycorticosterone (DOC) and dexamethasone (DM) on the modulation of CRF and beta EP containing neuron at the PVN of the hypothalamus. Rats were given either DM, DOC or GCA and adrenalectomized (ADX) and given either DM or DOC. At the end of treatment rats were transfused transcardially before sacrifice and the brain were dissected for immunohistochemical analysis. We found that immunostaining of the CRF containing neurons demonstrate a reduction in the number of positive neurons in DM treated rats. DOC and GCA treated rats showed the same result as in DM rats but the reduction is less. ADX, DM, DOC and GCA treated rats did not show any changes in the number of beta EP containing neurons but naloxone increased the number of beta EP containing neurons markedly. In conclusion, GCA and DOC have similar effects on CRF and beta EP containing neurons at the PVN.
    Matched MeSH terms: Neurons/metabolism
  17. Fulltext Phenotype microarrays reveal metabolic dysregulations of neurospheres derived from embryonic Ts1Cje mouse model of Down syndrome
    Seth EA, Lee HC, Yusof HHBM, Nordin N, Cheah YK, Ho ETW, et al.
    PLoS One, 2020;15(7):e0236826.
    PMID: 32730314 DOI: 10.1371/journal.pone.0236826
    Down syndrome (DS), is the most common cause of intellectual disability, and is characterized by defective neurogenesis during perinatal development. To identify metabolic aberrations in early neurogenesis, we profiled neurospheres derived from the embryonic brain of Ts1Cje, a mouse model of Down syndrome. High-throughput phenotypic microarray revealed a significant decrease in utilisation of 17 out of 367 substrates and significantly higher utilisation of 6 substrates in the Ts1Cje neurospheres compared to controls. Specifically, Ts1Cje neurospheres were less efficient in the utilisation of glucose-6-phosphate suggesting a dysregulation in the energy-producing pathway. T Cje neurospheres were significantly smaller in diameter than the controls. Subsequent preliminary study on supplementation with 6-phosphogluconic acid, an intermediate of glucose-6-phosphate metabolism, was able to rescue the Ts1Cje neurosphere size. This study confirmed the perturbed pentose phosphate pathway, contributing to defects observed in Ts1Cje neurospheres. We show for the first time that this comprehensive energetic assay platform facilitates the metabolic characterisation of Ts1Cje cells and confirmed their distinguishable metabolic profiles compared to the controls.
    Matched MeSH terms: Neurons/metabolism*
  18. Association between apoptotic neural tissue and cell proliferation in the adult teleost brain
    Lim FT, Ogawa S, Parhar IS
    Brain Res, 2016 11 01;1650:60-72.
    PMID: 27568467 DOI: 10.1016/j.brainres.2016.08.033
    Injury to neuronal tissues in the central nervous system (CNS) of mammals results in neural degeneration and sometime leads to loss of function, whereas fish retain a remarkable potential for neuro-regeneration throughout life. Thus, understanding the mechanism of neuro-regeneration in fish CNS would be useful to improve the poor neuro-regenerative capability in mammals. In the present study, we characterized a neuro-regenerative process in the brain of a cichlid, tilapia, Oreochromis niloticus. Morphological observations showed that the damaged brain region (habenula) successfully regrew and reinnervated axonal projections by 60 days post-damage. A fluorescent carbocyanine tracer, DiI tracing revealed a recovery of the major neuronal projection from the regenerated habenula to the interpenduncular nucleus by 60 days post-damage. TUNEL assay showed a significant increase of apoptotic cells (~234%, P<0.01) at one day post-damage, while the number of bromodeoxyuridine (BrdU)-positive proliferative cells were significantly increased (~92%, P<0.05) at 7 days post-damage compared with sham-control fish. To demonstrate a potential role of apoptotic activity in the neuro-regeneration, effects of degenerative neural tissue on cell proliferation were examined in vivo. Implantation of detached neural but not non-neural tissues into the cranial cavity significantly (P<0.01) increased the number of BrdU-positive cells nearby the implantation regions at 3 days after the implantation. Furthermore, local injection of the protein extract and cerebrospinal fluid collected from injured fish brain significantly induced cell proliferation in the brain. These results suggest that factor(s) derived from apoptotic neural cells may play a critical role in the neuro-regeneration in teleost brain.
    Matched MeSH terms: Neurons/metabolism
  19. The energetic brain - A review from students to students
    Bordone MP, Salman MM, Titus HE, Amini E, Andersen JV, Chakraborti B, et al.
    J Neurochem, 2019 10;151(2):139-165.
    PMID: 31318452 DOI: 10.1111/jnc.14829
    The past 20 years have resulted in unprecedented progress in understanding brain energy metabolism and its role in health and disease. In this review, which was initiated at the 14th International Society for Neurochemistry Advanced School, we address the basic concepts of brain energy metabolism and approach the question of why the brain has high energy expenditure. Our review illustrates that the vertebrate brain has a high need for energy because of the high number of neurons and the need to maintain a delicate interplay between energy metabolism, neurotransmission, and plasticity. Disturbances to the energetic balance, to mitochondria quality control or to glia-neuron metabolic interaction may lead to brain circuit malfunction or even severe disorders of the CNS. We cover neuronal energy consumption in neural transmission and basic ('housekeeping') cellular processes. Additionally, we describe the most common (glucose) and alternative sources of energy namely glutamate, lactate, ketone bodies, and medium chain fatty acids. We discuss the multifaceted role of non-neuronal cells in the transport of energy substrates from circulation (pericytes and astrocytes) and in the supply (astrocytes and microglia) and usage of different energy fuels. Finally, we address pathological consequences of disrupted energy homeostasis in the CNS.
    Matched MeSH terms: Neurons/metabolism
  20. Fulltext Morphological Evidence for Functional Crosstalk Between Multiple GnRH Systems in the Male Tilapia, Oreochromis niloticus
    Ogawa S, Parhar I
    Front Endocrinol (Lausanne), 2020;11:586.
    PMID: 32982977 DOI: 10.3389/fendo.2020.00586
    Gonadotropin-releasing hormone (GnRH) is a reproductive neuropeptide, which controls vertebrate reproduction. In most vertebrates, there are more than two GnRH orthologs in the brain. In cichlid fish, the Nile tilapia (Oreochromis niloticus), GnRH1 is the primary hypophysiotropic hormone, while GnRH2 and GnRH3 are non-hypophysiotropic but neuromodulatory in function. Hypophysiotropic GnRH neurons are thought to inter-communicate, while it remains unknown if hypophysiotropic and non-hypophysiotropic GnRH systems communicate with each other. In the present study, we examined interrelationship between three GnRH types using specific antibodies raised against their respective GnRH associated peptide (GAP) sequence. Double-immunofluorescence labeling coupled with confocal microscopy revealed that in sexually mature males, GnRH-GAP1-immunoreactive (-ir) processes are in proximities of GnRH-GAP3-ir cell somata in the terminal nerve, while GnRH-GAP1-ir cell somata were also accompanied by GnRH-GAP3-ir processes in the preoptic area. However, such interaction was not seen in immature males. Further, there was no interaction between GnRH-GAP2 and GnRH-GAP1 or GnRH-GAP3 neurons. Single cell gene expression analysis revealed co-expression of multiple GnRH receptor genes (gnrhr1 and gnrhr2) in three GnRH-GAP cell types. In mature males, high levels of gnrhr2 mRNA were expressed in GnRH-GAP1-ir cells. In immature males, gnrhr1 and gnrhr2 mRNAs are highly expressed in GnRH-GAP3-ir cells. These results suggest heterologous interactions between the three GnRH-GAP cell types and their potential functional interaction during different reproductive stages.
    Matched MeSH terms: Neurons/metabolism*
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