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Nitric oxide (NO), citrulline-NO cycle enzymes, glutamine synthetase, and oxidative status in kainic acid-mediated excitotoxicity in rat brain

Swamy M, Sirajudeen KN, Chandran G

Drug Chem Toxicol, 2009;32(4):326-31.
PMID: 19793024 DOI: 10.1080/01480540903130641

Neuronal excitation, involving the excitatory glutamate receptors, is recognized as an important underlying mechanism in neurodegenerative disorders. To understand their role in excitotoxicity, the nitric oxide synthase (NOS), argininosuccinate synthetase (AS), argininosuccinate lyase (AL), glutamine synthetase (GS), and arginase activities, along with the concentration of nitrate/nitrite, thiobarbituric acid-reactive substances (TBARS), and total antioxidant status (TAS), were estimated in the cerebral cortex, cerebellum, and brain stem of rats subjected to kainic acid-mediated excitotoxicity. The results of this study clearly demonstrated the increased production of NO by increased activity of NOS. The increased activities of AS and AL suggest the increased and effective recycling of citrulline to arginine in excitotoxicity, making NO production more effective and contributing to its toxic effects. The decreased activity of GS may favor the prolonged availability of glutamic acid, causing excitotoxicity, leading to neuronal damage. The increased formation of TBARS and decreased TAS indicate the presence of oxidative stress in excitotoxicity.

Matched MeSH terms: Neurons/drug effects*; Neurons/metabolism
Human neuronal cell protein responses to Nipah virus infection

Chang LY, Ali AR, Hassan SS, AbuBakar S

Virol J, 2007;4:54.
PMID: 17553172

Nipah virus (NiV), a recently discovered zoonotic virus infects and replicates in several human cell types. Its replication in human neuronal cells, however, is less efficient in comparison to other fully susceptible cells. In the present study, the SK-N-MC human neuronal cell protein response to NiV infection is examined using proteomic approaches.

Matched MeSH terms: Neurons/metabolism; Neurons/virology*
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.

Matched MeSH terms: Neurons/drug effects; Neurons/pathology
Fulltext Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring

Lim WL, Soga T, Parhar IS

Cell Tissue Res, 2014 Feb;355(2):409-23.
PMID: 24374911 DOI: 10.1007/s00441-013-1765-9

The migration of gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode to the preoptic area (POA) from embryonic day 13 is important for successful reproduction during adulthood. Whether maternal glucocorticoid exposure alters GnRH neuronal morphology and number in the offspring is unknown. This study determines the effect of maternal dexamethasone (DEX) exposure on enhanced green fluorescent protein (EGFP) driven by GnRH promoter neurons (TG-GnRH) in transgenic rats dual-labelled with GnRH immunofluorescence (IF-GnRH). The TG-GnRH neurons were examined in intact male and female rats at different postnatal ages, as a marker for GnRH promoter activity. Pregnant females were subcutaneously injected with DEX (0.1 mg/kg) or vehicle daily during gestation days 13-20 to examine the number of GnRH neurons in P0 male offspring. The total number of TG-GnRH neurons and TG-GnRH/IF-GnRH neuronal ratio increased from P0 and P5 stages to P47-52 stages, suggesting temporal regulation of GnRH promoter activity during postnatal development in intact rats. In DEX-treated P0 males, the number of IF-GnRH neurons decreased within the medial septum, organum vasculosom of the lamina terminalis (OVLT) and anterior hypothalamus. The percentage of TG-GnRH neurons with branched dendritic structures decreased in the OVLT of DEX-P0 males. These results suggest that maternal DEX exposure affects the number and dendritic development of early postnatal GnRH neurons in the OVLT/POA, which may lead to altered reproductive functions in adults.

Matched MeSH terms: Neurons/drug effects; Neurons/metabolism*
Fulltext Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses

Freiria-Oliveira AH, Blanch GT, Pedrino GR, Cravo SL, Murphy D, Menani JV, et al.

Am J Physiol Regul Integr Comp Physiol, 2015 Nov 01;309(9):R1082-91.
PMID: 26333788 DOI: 10.1152/ajpregu.00432.2014

Noradrenergic A2 neurons of the nucleus of the solitary tract (NTS) have been suggested to contribute to body fluid homeostasis and cardiovascular regulation. In the present study, we investigated the effects of lesions of A2 neurons of the commissural NTS (cNTS) on the c-Fos expression in neurons of the hypothalamic paraventricular (PVN) and supraoptic (SON) nuclei, arterial pressure, water intake, and urinary excretion in rats with plasma hyperosmolality produced by intragastric 2 M NaCl (2 ml/rat). Male Holtzman rats (280-320 g) received an injection of anti-dopamine-β-hydroxylase-saporin (12.6 ng/60 nl; cNTS/A2-lesion, n = 28) or immunoglobulin G (IgG)-saporin (12.6 ng/60 nl; sham, n = 24) into the cNTS. The cNTS/A2 lesions increased the number of neurons expressing c-Fos in the magnocellular PVN in rats treated with hypertonic NaCl (90 ± 13, vs. sham: 47 ± 20; n = 4), without changing the number of neurons expressing c-Fos in the parvocellular PVN or in the SON. Contrary to sham rats, intragastric 2 M NaCl also increased arterial pressure in cNTS/A2-lesioned rats (16 ± 3, vs. sham: 2 ± 2 mmHg 60 min after the intragastric load; n = 9), an effect blocked by the pretreatment with the vasopressin antagonist Manning compound (0 ± 3 mmHg; n = 10). In addition, cNTS/A2 lesions enhanced hyperosmolality-induced water intake (10.5 ± 1.4, vs. sham: 7.7 ± 0.8 ml/60 min; n = 8-10), without changing renal responses to hyperosmolality. The results suggest that inhibitory mechanisms dependent on cNTS/A2 neurons reduce water intake and vasopressin-dependent pressor response to an acute increase in plasma osmolality.

Matched MeSH terms: Adrenergic Neurons/cytology; Adrenergic Neurons/physiology*
Fulltext Social Isolation Modulates CLOCK Protein and Beta-Catenin Expression Pattern in Gonadotropin-Inhibitory Hormone Neurons in Male Rats

Teo CH, Soga T, Parhar IS

Front Endocrinol (Lausanne), 2017;8:225.
PMID: 28936198 DOI: 10.3389/fendo.2017.00225

Postweaning social isolation reduces the amplitude of the daily variation of CLOCK protein in the brain and induces lower reproductive activity. Gonadotropin-inhibitory hormone (GnIH) acts as an inhibitor in the reproductive system and has been linked to stress. Social isolation has been shown to lower neuronal activity of GnIH-expressing neurons in the dorsomedial hypothalamus (DMH). The exact mechanism by which social isolation may affect GnIH is still unclear. We investigated the impact of social isolation on regulatory cellular mechanisms in GnIH neurons. We examined via immunohistochemistry the expression of CLOCK protein at four different times throughout the day in GnIH cells tagged with enhanced fluorescent green protein (EGFP-GnIH) in 9-week-old adult male rats that have been raised for 6 weeks under postweaning social isolation and compared them with group-raised control rats of the same age. We also studied the expression of β-catenin-which has been shown to be affected by circadian proteins such as Bmal1-in EGFP-GnIH neurons to determine whether it could play a role in linking CLOCK in GnIH neurons. We found that social isolation modifies the pattern of CLOCK expression in GnIH neurons in the DMH. Socially isolated rats displayed greater CLOCK expression in the dark phase, while control rats displayed increased CLOCK expression in the light phase. Furthermore, β-catenin expression pattern in GnIH cells was disrupted by social isolation. This suggests that social isolation triggers changes in CLOCK and GnIH expression, which may be associated with an increase in nuclear β-catenin during the dark phase.

Matched MeSH terms: Neurons
Piper sarmentosum Roxb. confers neuroprotection on beta-amyloid (Aβ)-induced microglia-mediated neuroinflammation and attenuates tau hyperphosphorylation in SH-SY5Y cells

Yeo ETY, Wong KWL, See ML, Wong KY, Gan SY, Chan EWL

J Ethnopharmacol, 2018 May 10;217:187-194.
PMID: 29462698 DOI: 10.1016/j.jep.2018.02.025

ETHNOPHARMACOLOGICAL RELEVANCE: Piper sarmentosum Roxb. (PS), belonging to Piperaceae family, is an edible plant with medicinal properties. It is traditionally used by the Malays to treat headache and boost memory. Pharmacological studies revealed that PS exhibits anti-inflammatory, anti-oxidant, anti-acetylcholinesterase, and anti-depressant-like effects. In view of this, the present study aimed to investigate the anti-inflammatory actions of PS and its potential neuroprotective effects against beta-amyloid (Aβ)-induced microglia-mediated neurotoxicity.
MATERIALS AND METHODS: The inhibitory effects of hexane (LHXN), dichloromethane (LDCM), ethyl acetate (LEA) and methanol (LMEOH) extracts from leaves of PS on Aβ-induced production and mRNA expression of pro-inflammatory mediators in BV-2 microglial cells were assessed using colorimetric assay with Griess reagent, ELISA kit and real-time RT-PCR respectively. Subsequently, MTT reduction assay was used to evaluate the neuroprotective effects of PS leaf extracts against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y neuroblastoma cells. The levels of tau proteins phosphorylated at threonine 231 (pT231) and total tau proteins (T-tau) were determined using ELISA kits.
RESULTS: Polar extracts of PS leaves (LEA and LMEOH) reduced the Aβ-induced secretion of pro-inflammatory cytokines (IL-1β and TNF-α) in BV-2 cells by downregulating the mRNA expressions of pro-inflammatory cytokines. The inhibition of nitric oxide (NO) production could be due to the free radical scavenging activity of the extracts. In addition, conditioned media from Aβ-induced BV-2 cells pre-treated with LEA and LMEOH protected SH-SY5Y cells against microglia-mediated neurotoxicity. Further mechanistic study suggested that the neuroprotective effects were associated with the downregulation of phosphorylated tau proteins.
CONCLUSIONS: The present study suggests that polar extracts of PS leaves confer neuroprotection against Aβ-induced microglia-mediated neurotoxicity in SH-SY5Y cells by attenuating tau hyperphosphorylation through their anti-inflammatory actions and could be a potential therapeutic agent for Alzheimer's disease.

Matched MeSH terms: Neurons/drug effects*; Neurons/metabolism; Neurons/pathology
Fulltext Dual Actions of Mammalian and Piscine Gonadotropin-Inhibitory Hormones, RFamide-Related Peptides and LPXRFamide Peptides, in the Hypothalamic-Pituitary-Gonadal Axis

Ubuka T, Parhar I

Front Endocrinol (Lausanne), 2017;8:377.
PMID: 29375482 DOI: 10.3389/fendo.2017.00377

Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that decreases gonadotropin synthesis and release by directly acting on the gonadotrope or by decreasing the activity of gonadotropin-releasing hormone (GnRH) neurons. GnIH is also called RFamide-related peptide in mammals or LPXRFamide peptide in fishes due to its characteristic C-terminal structure. The primary receptor for GnIH is GPR147 that inhibits cAMP production in target cells. Although most of the studies in mammals, birds, and fish have shown the inhibitory action of GnIH in the hypothalamic-pituitary-gonadal (HPG) axis, several in vivo studies in mammals and many in vivo and in vitro studies in fish have shown its stimulatory action. In mouse, although the firing rate of the majority of GnRH neurons is decreased, a small population of GnRH neurons is stimulated by GnIH. In hamsters, GnIH inhibits luteinizing hormone (LH) release in the breeding season when their endogenous LH level is high but stimulates LH release in non-breeding season when their LH level is basal. Besides different effects of GnIH on the HPG axis depending on the reproductive stages in fish, higher concentration or longer duration of GnIH administration can stimulate their HPG axis. These results suggest that GnIH action in the HPG axis is modulated by sex-steroid concentration, the action of neuroestrogen synthesized by the activity of aromatase stimulated by GnIH, estrogen membrane receptor, heteromerization and internalization of GnIH, GnRH, and estrogen membrane receptors. The inhibitory and stimulatory action of GnIH in the HPG axis may have a physiological role to maintain reproductive homeostasis according to developmental and reproductive stages.

Matched MeSH terms: Neurons
Fulltext Isothiocyanate from Moringa oleifera seeds mitigates hydrogen peroxide-induced cytotoxicity and preserved morphological features of human neuronal cells

Jaafaru MS, Nordin N, Shaari K, Rosli R, Abdull Razis AF

PLoS One, 2018;13(5):e0196403.
PMID: 29723199 DOI: 10.1371/journal.pone.0196403

Reactive oxygen species are well known for induction of oxidative stress conditions through oxidation of vital biomarkers leading to cellular death via apoptosis and other process, thereby causing devastative effects on the host organs. This effect is believed to be linked with pathological alterations seen in several neurodegenerative disease conditions. Many phytochemical compounds proved to have robust antioxidant activities that deterred cells against cytotoxic stress environment, thus protect apoptotic cell death. In view of that we studied the potential of glucomoringin-isothiocyanate (GMG-ITC) or moringin to mitigate the process that lead to neurodegeneration in various ways. Neuroprotective effect of GMG-ITC was performed on retinoic acid (RA) induced differentiated neuroblastoma cells (SHSY5Y) via cell viability assay, flow cytometry analysis and fluorescence microscopy by means of acridine orange and propidium iodide double staining, to evaluate the anti-apoptotic activity and morphology conservation ability of the compound. Additionally, neurite surface integrity and ultrastructural analysis were carried out by means of scanning and transmission electron microscopy to assess the orientation of surface and internal features of the treated neuronal cells. GMG-ITC pre-treated neuron cells showed significant resistance to H2O2-induced apoptotic cell death, revealing high level of protection by the compound. Increase of intracellular oxidative stress induced by H2O2 was mitigated by GMG-ITC. Thus, pre-treatment with the compound conferred significant protection to cytoskeleton and cytoplasmic inclusion coupled with conservation of surface morphological features and general integrity of neuronal cells. Therefore, the collective findings in the presence study indicated the potentials of GMG-ITC to protect the integrity of neuron cells against induced oxidative-stress related cytotoxic processes, the hallmark of neurodegenerative diseases.

Matched MeSH terms: Neurons/cytology; Neurons/drug effects*; Neurons/metabolism
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: Neurons/drug effects*; Neurons/metabolism; Neurons/pathology
d-galactose and aluminium chloride induced rat model with cognitive impairments

Chiroma SM, Mohd Moklas MA, Mat Taib CN, Baharuldin MTH, Amon Z

Biomed Pharmacother, 2018 Jul;103:1602-1608.
PMID: 29864948 DOI: 10.1016/j.biopha.2018.04.152

Cognitive impairments and cholinergic dysfunctions have been well reported in old age disorders including Alzheimer's disease (AD). d-galactose (D-gal) has been reported as a senescence agent while aluminium act as a neurotoxic metal, but little is known about their combined effects at different doses. The aim of this study was to establish an animal model with cognitive impairments by comparing the effects of different doses of co-administrated D-gal and aluminium chloride (AlCl3). In this study male albino wistar rats were administered with D-gal 60 mg/kg.bwt intra peritoneally (I.P) injected and AlCl3 (100, 200, or 300 mg/kg.bwt.) was orally administered once daily for 10 consecutive weeks. Performance of the rats were evaluated through behavioural assessments; Morris water maze (MWM) and open field tests (OFT); histopathological examination was performed on the hippocampus; moreover biochemical measurements of acetylcholinesterase (AChE) and hyperphosphorylated tau protein (p-tau) were examined. The results of this experiment on rats treated with D-gal 60 + AlCl3 200 mg/kg.bwt showed near ideal cognitive impairments. The rats exhibited an obvious memory and learning deficits, marked neuronal loss in hippocampus, showed increase in AChE activities and high expression of p-tau within the tissues of the brain. This study concludes that D-gal 60 + AlCl3 200 mg/kg.bwt as the ideal dose for mimicking AD like cognitive impairments in albino wistar rats. It is also crucial to understand the pathogenesis of this neurodegenerative disease and for drug discovery.

Matched MeSH terms: Neurons/drug effects; Neurons/metabolism; Neurons/pathology
The protective mechanisms of polydatin in cerebral ischemia

Tang KS, Tan JS

Eur J Pharmacol, 2019 Jan 05;842:133-138.
PMID: 30385347 DOI: 10.1016/j.ejphar.2018.10.039

The prevalence of stroke is high in both developing and developed nations. It causes a heavy social and financial burden to the sufferers and their caregivers. Thrombolytic therapy is the only pharmacological treatment available for stroke. However, thrombolytic agents do not provide substantial improvement on long term motor and cognitive disabilities. Thus, there is a need to explore for new compounds that can halt or reverse the deterioration of neurons in the stroke patients' brain. Polydatin, a precursor of resveratrol, is a natural stilbene commonly found in food. This review article describes how different parameters were altered with ischemic injury and polydatin treatment, why it is important and how it could be beneficial or useful in future studies. Our review of polydatin provides convincing evidence regarding the potential of polydatin to be developed into preventive or therapeutic products for ischemic stroke. Nevertheless, additional studies are necessary in order to properly elucidate the biological mechanisms of polydatin, especially its molecular mechanisms of protection and target proteins, in cerebral ischemia.

Matched MeSH terms: Neurons
Fulltext Neuronal Cell Death and Mouse (Mus musculus) Behaviour Induced by Bee Venom

Oktiansyah R, Juliandi B, Widayati KA, Juniantito V

Trop Life Sci Res, 2018 Jul;29(2):1-11.
PMID: 30112137 DOI: 10.21315/tlsr2018.29.2.1

Neuronal cell death can occur in a tissue or organ, including the brain, which affects memory. The objectives of this study were to determine the dose of bee venom that causes neuronal death and analyse the alteration of mouse behaviour, focusing in particular on spatial memory. Fifteen male mice of Deutsche Denken Yoken (DDY) strain were divided into control and treatment groups. Bee venom was injected six times for two weeks intraperitoneally with 1.88 mg/kg, 3.76 mg/kg, 5.6 mg/kg, and 7.48 mg/kg doses of venom. Brain histology was studied using haematoxylin-eosin stained paraffin embedded 5 μm coronal sections. A Y maze test was used to assay behaviour. Parameters observed were the number of dead neurons and the percentage of mice with altered behaviour. ANOVA showed that the effects of bee venom were significantly different in the case of the neuronal death parameter but were not significantly different in the case of the mice behaviour parameter. Duncan's Multiple Range Test (DMRT) demonstrated that P4 (7.48 mg/kg) gave the highest effect of bee venom to promote neuronal death.

Matched MeSH terms: Neurons
Fulltext HMGB1: A Common Biomarker and Potential Target for TBI, Neuroinflammation, Epilepsy, and Cognitive Dysfunction

Paudel YN, Shaikh MF, Chakraborti A, Kumari Y, Aledo-Serrano Á, Aleksovska K, et al.

Front Neurosci, 2018;12:628.
PMID: 30271319 DOI: 10.3389/fnins.2018.00628

High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein released by glia and neurons upon inflammasome activation and activates receptor for advanced glycation end products (RAGE) and toll-like receptor (TLR) 4 on the target cells. HMGB1/TLR4 axis is a key initiator of neuroinflammation. In recent days, more attention has been paid to HMGB1 due to its contribution in traumatic brain injury (TBI), neuroinflammatory conditions, epileptogenesis, and cognitive impairments and has emerged as a novel target for those conditions. Nevertheless, HMGB1 has not been portrayed as a common prognostic biomarker for these HMGB1 mediated pathologies. The current review discusses the contribution of HMGB1/TLR4/RAGE signaling in several brain injury, neuroinflammation mediated disorders, epileptogenesis and cognitive dysfunctions and in the light of available evidence, argued the possibilities of HMGB1 as a common viable biomarker of the above mentioned neurological dysfunctions. Furthermore, the review also addresses the result of preclinical studies focused on HMGB1 targeted therapy by the HMGB1 antagonist in several ranges of HMGB1 mediated conditions and noted an encouraging result. These findings suggest HMGB1 as a potential candidate to be a common biomarker of TBI, neuroinflammation, epileptogenesis, and cognitive dysfunctions which can be used for early prediction and progression of those neurological diseases. Future study should explore toward the translational implication of HMGB1 which can open the windows of opportunities for the development of innovative therapeutics that could prevent several associated HMGB1 mediated pathologies discussed herein.

Matched MeSH terms: Neurons
Expression of RING Finger Protein 38 in Serotonergic Neurons in the Brain of Nile Tilapia, Oreochromis niloticus

Cham KL, Soga T, Parhar IS

Front Neuroanat, 2018;12:109.
PMID: 30574074 DOI: 10.3389/fnana.2018.00109

Serotonin (5-hydroxytryptamine, 5-HT) is one of the major neurotransmitters, modulating diverse behaviours and physiological functions. Really interesting new gene (RING) finger protein 38 (RNF38) is an E3 ubiquitin ligase whose function remains unclear. A recent study has shown a possible regulatory relationship between RNF38 and the 5-HT system. Therefore, to gain insight into the role of RNF38 in the central 5-HT system, we identified the neuroanatomical location of 5-HT positive cells and investigated the relationship between RNF38 and the 5-HT system in the brain of the Nile tilapia, Oreochromis niloticus. Immunocytochemistry revealed three neuronal populations of 5-HT in the brain of tilapia; the paraventricular organ (PVO), the dorsal and ventral periventricular pretectal nuclei (PPd and PPv), and, the superior and inferior raphe (SR and IR). The 5-HT neuronal number was highest in the raphe (90.4 in SR, 284.6 in IR), followed by the pretectal area (22.3 in PPd, 209.8 in PPv). Double-label immunocytochemistry showed that the majority of 5-HT neurons express RNF38 nuclear proteins (66.5% in PPd; 77.9% in PPv; 35.7% in SR; 49.1% in IR). These findings suggest that RNF38 could be involved in E3 ubiquitination in the central 5-HT system.

Matched MeSH terms: Neurons
Fulltext TRPM2 Channel in Microglia as a New Player in Neuroinflammation Associated With a Spectrum of Central Nervous System Pathologies

Malko P, Syed Mortadza SA, McWilliam J, Jiang LH

Front Pharmacol, 2019;10:239.
PMID: 30914955 DOI: 10.3389/fphar.2019.00239

Microglial cells in the central nervous system (CNS) are crucial in maintaining a healthy environment for neurons to function properly. However, aberrant microglial cell activation can lead to excessive generation of neurotoxic proinflammatory mediators and neuroinflammation, which represents a contributing factor in a wide spectrum of CNS pathologies, including ischemic stroke, traumatic brain damage, Alzheimer's disease, Parkinson's disease, multiple sclerosis, psychiatric disorders, autism spectrum disorders, and chronic neuropathic pain. Oxidative stress is a salient and common feature of these conditions and has been strongly implicated in microglial cell activation and neuroinflammation. The transient receptor potential melastatin-related 2 (TRPM2) channel, an oxidative stress-sensitive calcium-permeable cationic channel, is highly expressed in microglial cells. In this review, we examine the recent studies that provide evidence to support an important role for the TRPM2 channel, particularly TRPM2-mediated Ca2+ signaling, in mediating microglial cell activation, generation of proinflammatory mediators and neuroinflammation, which are of relevance to CNS pathologies. These findings lead to a growing interest in the TRPM2 channel, a new player in neuroinflammation, as a novel therapeutic target for CNS diseases.

Matched MeSH terms: Neurons
Fulltext Prevention of brain hypoperfusion-induced neurodegeneration in rat’s hippocampus by black cumin fixed oil treatment

Marwan Saad Azzubaidi, Al-Ani, Imad Matloub, Anil Kumar Saxena, Ghasak Ghazi Faisal

International Medical Journal Malaysia, 2018;17(1):103-112.
MyJurnal

Introduction: The oil extract of black cumin seeds Nigella sativa (NSO) demonstrated considerable
preservation of spatial cognitive functions in rats subjected to chronic brain hypoperfusion (CBH). The hippocampal CA1 region pyramidal cells are the earliest neurons suffering neurodegeneration following CBH. Objective: The current study was devoted to assess the protective effects of Nigella sativa (NSO) treatment on CA1 hippocampal pyramidal cells of rats subjected to chronic brain hypoperfusion (CBH) that was achieved through permanent two vessel occlusion (2VO) procedure. Methods: Twenty four rats were equally divided into three groups; sham control, untreated 2VO and NSO treated group (2VO with daily oral NSO treatment. After the 10th postoperative week coronal sections of the hippocampus were collected for histopathological and electron microscopical examinations. Results: The number of viable pyramidal cells within CA1 hippocampal region in sham control and NSO treated groups was significantly higher than that of untreated 2VO group, while the difference was not significant when comparing the viable pyramidal cells number of sham control with NSO treated groups. Furthermore, 2VO group showed marked intracellular ultrastructural distortions that were less pronounced in NSO treated group. Conclusion: NSO displayed a robust potential to protect hippocampal pyramidal cells from CBH induced neurodegeneration putting forward its prospective neuroprotective activity against age related cognitive decline of Alzheimer’s disease and vascular dementia.

Matched MeSH terms: Neurons
Stress induces reinstatement of extinguished cocaine conditioned place preference by a sequential signaling via neuropeptide S, orexin, and endocannabinoid

Chou YH, Hor CC, Lee MT, Lee HJ, Guerrini R, Calo G, et al.

Addict Biol, 2020 Oct 19.
PMID: 33078457 DOI: 10.1111/adb.12971

Neurons containing neuropeptide S (NPS) and orexins are activated during stress. Previously, we reported that orexins released during stress, via orexin OX1 receptors (OX1 Rs), contribute to the reinstatement of cocaine seeking through endocannabinoid/CB1 receptor (CB1 R)-mediated dopaminergic disinhibition in the ventral tegmental area (VTA). Here, we further demonstrated that NPS released during stress is an up-stream activator of this orexin-endocannabinoid cascade in the VTA, leading to the reinstatement of cocaine seeking. Mice were trained to acquire cocaine conditioned place preference (CPP) by context-pairing cocaine injections followed by the extinction training with context-pairing saline injections. Interestingly, the extinguished cocaine CPP in mice was significantly reinstated by intracerebroventricular injection (i.c.v.) of NPS (1 nmol) in a manner prevented by intraperitoneal injection (i.p.) of SHA68 (50 mg/kg), an NPS receptor antagonist. This NPS-induced cocaine reinstatement was prevented by either i.p. or intra-VTA microinjection (i.vta.) of SB-334867 (15 mg/kg, i.p. or 15 nmol, i.vta.) and AM 251 (1.1 mg/kg, i.p. or 30 nmol, i.vta.), antagonists of OX1 Rs and CB1 Rs, respectively. Besides, NPS (1 nmol, i.c.v.) increased the number of c-Fos-containing orexin neurons in the lateral hypothalamus (LH) and increased orexin-A level in the VTA. The latter effect was blocked by SHA68. Furthermore, a 30-min restraint stress in mice reinstated extinguished cocaine CPP and was prevented by SHA68. These results suggest that NPS is released upon stress and subsequently activates LH orexin neurons to release orexins in the VTA. The released orexins then reinstate extinguished cocaine CPP via an OX1 R- and endocannabinoid-CB1 R-mediated signaling in the VTA.

Matched MeSH terms: Neurons
Fulltext Exploring Changes in Thalamus Metabolites as Diagnostic Biomarkers in Idiopathic Generalised Epilepsy Patients Using Magnetic Resonance Spectroscopy

Abedi-Firouzjah R, Rostamzadeh A, Banaei A, Shafiee M, Moghaddam ZM, Vafapour H

Malays J Med Sci, 2020 Feb;27(1):78-86.
PMID: 32158347 DOI: 10.21315/mjms2020.27.1.8

Introduction: Idiopathic generalised epilepsy (IGE) refers to a group of epilepsies resulting from the activation of neurons in the whole brain. This study aimed to evaluate the metabolite changes in thalamus as diagnostic biomarkers in IGE patients compared to healthy individuals using magnetic resonance spectroscopy (MRS) technique.
Methods: The MRS was performed on 35 IGE patients (26 women and 11 men) with average age of 32 (ranged from 18 to 43) and 35 healthy individuals (13 women and 22 men) with average age of 31 (ranged from 21 to 50) as the control group. The levels of N-acetylaspartate (NAA), creatine (Cr) and choline (Cho) were measured using MRS. The NAA/Cr and NAA/Cho ratios were calculated for all participants. These values were statistically compared using t-test between the groups.
Results: The NAA had significant lower values in IGE patients, 9.6 (SD = 0.8) and 9.9 (SD = 0.7) for right and left thalamus, respectively, compared to 10.9 (SD = 0.9) and 10.7 (SD = 0.9) in control group. The Cr values in the left side of thalamus were significantly higher in IGE patients (6.7 [SD = 0.8] versus 5.8 [SD = 0.5]); however, there was no difference in right thalamus. Measurements showed no difference for amounts of Cho between the groups in both sides of thalamus. The NAA/Cr ratio was 1.48 (SD = 0.14) and 1.48 (SD = 0.16) for right and left thalamus, respectively, in IGE patients in comparison with 1.83 (SD = 0.2) and 1.86 (SD = 0.26) in controls. There was no meaningful variation between the NAA/Cho ratio of the right and left thalamus among the groups.
Conclusion: Thalamic NAA, Cr and NAA/Cr ratio values in IGE patients showed statistical differences compared to healthy individuals. Evaluating metabolites variations in thalamus using MRS is suggested for differentiating IGE patients from healthy individuals.

Matched MeSH terms: Neurons
Fulltext Tualang Honey Improves Memory and Prevents Hippocampal Changes in Prenatally Stressed Rats

Abd Aziz CB, Hasim H, Zakaria R, Ahmad AH

Turk J Pharm Sci, 2020 Dec 23;17(6):620-625.
PMID: 33389951 DOI: 10.4274/tjps.galenos.2019.21548

Objectives: This study investigated whether the alterations in memory and hippocampus morphology and levels of malondialdehyde (MDA) and N-methyl-D-aspartate (NMDA) receptor in the hippocampus of adult rats after prenatal stress could be prevented by administration of Tualang honey (TH).
Materials and Methods: Twenty-four pregnant rats were randomly grouped into a control group (C), a stress group (S), and a stress group treated with TH. Eight male pups from each group were randomly chosen and they were sacrificed at eight or ten weeks of age following the novel object recognition test. Their brains were removed and histological changes and levels of MDA and NMDA receptors in the hippocampus were determined.
Results: The offspring from TH group showed significantly increased preference index (p<0.05) with higher neuronal number compared to S group. A significantly lower level of MDA and NMDA receptors were shown in TH group (P<0.01; P<0.05 respectively) compared to S group. The parameters investigated were not significantly different between C and TH groups.
Conclusion: The study has shown that memory alteration, changes in hippocampus histology, MDA and NMDA receptor levels could be prevented by TH administration during prenatal stress. The results suggest the beneficial effects of Tualang honey in prenatally stressed rat offspring.

Matched MeSH terms: Neurons

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