MyMedR

Displaying publications 121 - 140 of 290 in total

Abstract:

Sort:

Motor neurone disease

Tay CH, Jek WT

Med J Malaya, 1972 Jun;26(4):272-7.
PMID: 5069417
Matched MeSH terms: Motor Neurons*
The effects of metallothionein in paraquat-induced Parkinson disease model of zebrafish

Mohamad Najib NH, Yahaya MF, Das S, Teoh SL

Int J Neurosci, 2023 Dec;133(8):822-833.
PMID: 34623211 DOI: 10.1080/00207454.2021.1990916

INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Metallothionein has been shown to act as a neuroprotectant in various brain injury. Thus, this study aims to identify the effects of full-length human metallothionein 2 peptide (hMT2) in paraquat-induced brain injury in the zebrafish.
METHODOLOGY: A total of 80 adult zebrafish were divided into 4 groups namely control, paraquat-treated, pre-hMT2-treated, and post-hMT2-treated groups. Fish were treated with paraquat intraperitoneally every 3 days for 15 days. hMT2 were injected intracranially on day 0 (pre-treated group) and day 16 (post-treated group). Fish were sacrificed on day 22 and the brains were collected for qPCR, ELISA and immunohistochemistry analysis.
RESULTS: qPCR analysis showed that paraquat treatment down-regulated the expression of genes related to dopamine activity and biosynthesis (dat and th1) and neuroprotective agent (bdnf). Paraquat treatment also up-regulated the expression of the mt2, smtb and proinflammatory genes (il-1α, il-1β, tnf-α and cox-2). hMT2 treatment was able to reverse the effects of paraquat. Lipid peroxidation decreased in the paraquat and pre-hMT2-treated groups. However, lipid peroxidation increased in the post-hMT2-treated group. Paraquat treatment also led to a reduction of dopaminergic neurons while their numbers showed an increase following hMT2 treatment.
CONCLUSION: Paraquat has been identified as one of the pesticides that can cause the death of dopaminergic neurons and affect dopamine biosynthesis. Treatment with exogenous hMT2 could reverse the effects of paraquat in the zebrafish brain.

Matched MeSH terms: Dopaminergic Neurons/metabolism
Immunotherapies for Parkinson's Disease: Progression of Clinical Development

Teng JS, Ooi YY, Chye SM, Ling APK, Koh RY

CNS Neurol Disord Drug Targets, 2021;20(9):802-813.
PMID: 34042040 DOI: 10.2174/1871527320666210526160926

Parkinson's disease is a common neurodegenerative disease affecting the movement and well-being of most elderly. The manifestations of Parkinson's disease often include resting tremor, stiffness, bradykinesia, and muscular rigidity. The typical hallmark of Parkinson's disease is the destruction of neurons in the substantia nigra and the presence of Lewy bodies in different compartments of the central nervous system. Due to various limitations to the currently available treatments, immunotherapies have emerged to be the new approach to Parkinson's disease treatment. This approach shows some positive outcomes on the efficacy by removing the aggregated species of alpha-synuclein, which is believed to be one of the causes of Parkinson's disease. In this review, an overview of how alpha-synuclein contributes to Parkinson's disease and the effects of a few new immunotherapeutic treatments, including BIIB054 (cinpanemab), MEDI1341, AFFITOPE, and PRX002 (prasinezumab) that are currently under clinical development, will be discussed.

Matched MeSH terms: Neurons/drug effects
Genomic instantiation of consciousness in neurons through a biophoton field theory

Cacha LA, Poznanski RR

J Integr Neurosci, 2014 Jun;13(2):253-92.
PMID: 25012712 DOI: 10.1142/S0219635214400081

A theoretical framework is developed based on the premise that brains evolved into sufficiently complex adaptive systems capable of instantiating genomic consciousness through self-awareness and complex interactions that recognize qualitatively the controlling factors of biological processes. Furthermore, our hypothesis assumes that the collective interactions in neurons yield macroergic effects, which can produce sufficiently strong electric energy fields for electronic excitations to take place on the surface of endogenous structures via alpha-helical integral proteins as electro-solitons. Specifically the process of radiative relaxation of the electro-solitons allows for the transfer of energy via interactions with deoxyribonucleic acid (DNA) molecules to induce conformational changes in DNA molecules producing an ultra weak non-thermal spontaneous emission of coherent biophotons through a quantum effect. The instantiation of coherent biophotons confined in spaces of DNA molecules guides the biophoton field to be instantaneously conducted along the axonal and neuronal arbors and in-between neurons and throughout the cerebral cortex (cortico-thalamic system) and subcortical areas (e.g., midbrain and hindbrain). Thus providing an informational character of the electric coherence of the brain - referred to as quantum coherence. The biophoton field is realized as a conscious field upon the re-absorption of biophotons by exciplex states of DNA molecules. Such quantum phenomenon brings about self-awareness and enables objectivity to have access to subjectivity in the unconscious. As such, subjective experiences can be recalled to consciousness as subjective conscious experiences or qualia through co-operative interactions between exciplex states of DNA molecules and biophotons leading to metabolic activity and energy transfer across proteins as a result of protein-ligand binding during protein-protein communication. The biophoton field as a conscious field is attributable to the resultant effect of specifying qualia from the metabolic energy field that is transported in macromolecular proteins throughout specific networks of neurons that are constantly transforming into more stable associable representations as molecular solitons. The metastability of subjective experiences based on resonant dynamics occurs when bottom-up patterns of neocortical excitatory activity are matched with top-down expectations as adaptive dynamic pressures. These dynamics of on-going activity patterns influenced by the environment and selected as the preferred subjective experience in terms of a functional field through functional interactions and biological laws are realized as subjectivity and actualized through functional integration as qualia. It is concluded that interactionism and not information processing is the key in understanding how consciousness bridges the explanatory gap between subjective experiences and their neural correlates in the transcendental brain.

Matched MeSH terms: Neurons/physiology*
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*
Fulltext Recurrent Bell's palsy in a young woman

Ngow HA, Wan Khairina WM, Hamidon BB

Singapore Med J, 2008 Oct;49(10):e278-80.
PMID: 18946598

Bell's palsy is a benign lower motor neuron facial nerve disorder. It is almost always unilateral. We report a 20-year-old nulliparous woman with five episodes of recurrent Bell's palsy. A review of recent medical literature revealed a paucity of case reports involving an individual with five episodes of recurrent Bell's palsy, with none found in Asian neurology medical literature. Despite the multiple episodes of Bell's palsy recurrences, the patient did not suffer much neurological sequelae from the disease.

Matched MeSH terms: Motor Neurons/pathology
Fulltext A Hot Cross Bun sign from diffusion tensor imaging and tractography perspective

Loh KB, Rahmat K, Lim SY, Ramli N

Neurol India, 2011 Mar-Apr;59(2):266-9.
PMID: 21483130 DOI: 10.4103/0028-3886.79143

A "Hot Cross Bun" sign on T2-weighted MRI was described as a result of selective loss of myelinated transverse pontocerebellar fibers and neurons in the pontine raphe with preservation of the pontine tegmentum and corticospinal tracts (CST). However, neuropathologic studies showed contradicting results with no sparing of the CST. This is a pictorial and quantitative demonstration of the sign on diffusion tensor imaging and tractography, which provides the imaging evidence that is consistent with neuropathologic findings.

Matched MeSH terms: Neurons/pathology
Localization of the spinal nucleus of accessory nerve in rat: a horseradish peroxidase study

Ullah M, Mansor O, Ismail ZI, Kapitonova MY, Sirajudeen KN

J Anat, 2007 Apr;210(4):428-38.
PMID: 17428204

The spinal nucleus of the accessory nerve (SNA) comprises the group of somata (perikarya) of motor neurons that supply the sternocleidomastoid and trapezius muscles. There are many conflicting views regarding the longitudinal extent and topography of the SNA, even in the same species, and these disagreements prompted the present investigation. Thirty Sprague-Dawley rats (15 males, 15 females) were used. The SNA was localized by retrograde axonal transport of horseradish peroxidase. Longitudinally, the SNA was found to be located in the caudal part (caudal 0.9-1.2 mm) of the medulla oblongata, the whole lengths of cervical spinal cord segments C1, C2, C3, C4, C5 and rostral fourth of C6. In the caudal part of the medulla oblongata, the SNA was represented by a group of perikarya of motor neurons lying immediately ventrolateral to the pyramidal fibres that were passing dorsolaterally after their decussation. In the spinal cord, the motor neuronal somata of the SNA were located in the dorsomedial and central columns at C1, in the dorsomedial, central and ventrolateral columns at C2 and in the ventrolateral column only at C3, C4, C5 and rostral quarter of C6. The perikarya of motor neurons supplying the sternocleidomastoid were located in the caudal part (caudal 0.9-1.2 mm) of the medulla oblongata ventrolateral to the pyramidal fibres that were passing dorsolaterally after their decussation. They were also located in the dorsomedial and central columns at C1, in the dorsomedial, central and ventrolateral columns at C2 and only in the ventrolateral column at the rostral three-quarters of C3. The perikarya of motor neurons supplying the trapezius muscle were located in the ventrolateral column only in the caudal three-quarters of C2, the whole lengths of C3, C4 and C5, and in the rostral quarter of C6.

Matched MeSH terms: Motor Neurons/cytology
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*
Effects of action observation on corticospinal excitability: Muscle specificity, direction, and timing of the mirror response

Naish KR, Houston-Price C, Bremner AJ, Holmes NP

Neuropsychologia, 2014 11;64:331-48.
PMID: 25281883 DOI: 10.1016/j.neuropsychologia.2014.09.034

Many human behaviours and pathologies have been attributed to the putative mirror neuron system, a neural system that is active during both the observation and execution of actions. While there are now a very large number of papers on the mirror neuron system, variations in the methods and analyses employed by researchers mean that the basic characteristics of the mirror response are not clear. This review focuses on three important aspects of the mirror response, as measured by modulations in corticospinal excitability: (1) muscle specificity; (2) direction; and (3) timing of modulation. We focus mainly on electromyographic (EMG) data gathered following single-pulse transcranial magnetic stimulation (TMS), because this method provides precise information regarding these three aspects of the response. Data from paired-pulse TMS paradigms and peripheral nerve stimulation (PNS) are also considered when we discuss the possible mechanisms underlying the mirror response. In this systematic review of the literature, we examine the findings of 85 TMS and PNS studies of the human mirror response, and consider the limitations and advantages of the different methodological approaches these have adopted in relation to discrepancies between their findings. We conclude by proposing a testable model of how action observation modulates corticospinal excitability in humans. Specifically, we propose that action observation elicits an early, non-specific facilitation of corticospinal excitability (at around 90ms from action onset), followed by a later modulation of activity specific to the muscles involved in the observed action (from around 200ms). Testing this model will greatly advance our understanding of the mirror mechanism and provide a more stable grounding on which to base inferences about its role in human behaviour.

Matched MeSH terms: Mirror Neurons/physiology*
The role of multifunctional drug therapy against carbamate induced neuronal toxicity during acute and chronic phase in rats

Chahal KS, Prakash A, Majeed AB

Environ Toxicol Pharmacol, 2015 Jul;40(1):220-9.
PMID: 26151868 DOI: 10.1016/j.etap.2015.06.002

The current study has been designed to examine the effect of multifunctional drug therapy on carbofuran induced acute (2.187 mg/kg, s.c.) and sub-acute (0.2187 mg/kg, s.c.) neurotoxicity in male wistar rats. Drug treatment which includes nimodipine (Ca(2+) channel blocker), diazepam, ropinirole (dopamine agonist) and GSPE (antioxidant) was started 2h after carbofuran administration. Morris water maze was employed for aiming spatial memory. Narrow beam walk and rotarod were employed for testing motor functions. Brain acetylcholinesterase activity, thiobarbituric acid reactive species, nitrite, reduced glutathione, catalase levels, and mitochondrial complexes were also estimated. Carbofuran treatment resulted in significant development of cognitive and motor functions manifested as impairment in learning and memory along with increased thiobarbituric acid reactive species, nitrite levels and decreased acetylcholinesterase activity, reduced glutathione, catalase levels, and mitochondrial complexes. The standard antidote therapy (atropine) was not able to provide neuroprotection but was able to provide symptomatic relief. The multifunctional drug therapy attenuated carbofuran induced cognitive and motor dysfunction, acetylcholinesterase activity and other biochemical parameters. The triple combination in sub-acute study may be avoided in future as two drug combinations provide adequate neuroprotection. Thus it can be concluded that standard antidotal therapy may not provide neuroprotection while the multifunctional drug therapy offers neuroprotection against carbofuran and may dramatically increase survival and life quality.

Matched MeSH terms: Neurons/drug effects*
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*
Mouse model of intracerebellar haemorrhage

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.

Matched MeSH terms: Neurons/pathology
Fulltext Promoting effect of small molecules in cardiomyogenic and neurogenic differentiation of rat bone marrow-derived mesenchymal stem cells

Khanabdali R, Saadat A, Fazilah M, Bazli KF, Qazi RE, Khalid RS, et al.

Drug Des Devel Ther, 2016;10:81-91.
PMID: 26766903 DOI: 10.2147/DDDT.S89658

Small molecules, growth factors, and cytokines have been used to induce differentiation of stem cells into different lineages. Similarly, demethylating agents can trigger differentiation in adult stem cells. Here, we investigated the in vitro differentiation of rat bone marrow mesenchymal stem cells (MSCs) into cardiomyocytes by a demethylating agent, zebularine, as well as neuronal-like cells by β-mercaptoethanol in a growth factor or cytokines-free media. Isolated bone marrow-derived MSCs cultured in Dulbecco's Modified Eagle's Medium exhibited a fibroblast-like morphology. These cells expressed positive markers for CD29, CD44, and CD117 and were negative for CD34 and CD45. After treatment with 1 μM zebularine for 24 hours, the MSCs formed myotube-like structures after 10 days in culture. Expression of cardiac-specific genes showed that treated MSCs expressed significantly higher levels of cardiac troponin-T, Nkx2.5, and GATA-4 compared with untreated cells. Immunocytochemical analysis showed that differentiated cells also expressed cardiac proteins, GATA-4, Nkx 2.5, and cardiac troponin-T. For neuronal differentiation, MSCs were treated with 1 and 10 mM β-mercaptoethanol overnight for 3 hours in complete and serum-free Dulbecco's Modified Eagle's Medium, respectively. Following overnight treatment, neuron-like cells with axonal and dendritic-like projections originating from the cell body toward the neighboring cells were observed in the culture. The mRNA expression of neuronal-specific markers, Map2, Nefl, Tau, and Nestin, was significantly higher, indicating that the treated cells differentiated into neuronal-like cells. Immunostaining showed that differentiated cells were positive for the neuronal markers Flk, Nef, Nestin, and β-tubulin.

Matched MeSH terms: Neurons/cytology*
Molecular, cellular, morphological, physiological and behavioral aspects of gonadotropin-inhibitory hormone

Ubuka T, Son YL, Tsutsui K

Gen Comp Endocrinol, 2016 Feb 1;227:27-50.
PMID: 26409890 DOI: 10.1016/j.ygcen.2015.09.009

Gonadotropin-inhibitory hormone (GnIH) is a hypothalamic neuropeptide that was isolated from the brains of Japanese quail in 2000, which inhibited luteinizing hormone release from the anterior pituitary gland. Here, we summarize the following fifteen years of researches that investigated on the mechanism of GnIH actions at molecular, cellular, morphological, physiological, and behavioral levels. The unique molecular structure of GnIH peptide is in its LPXRFamide (X=L or Q) motif at its C-terminal. The primary receptor for GnIH is GPR147. The cell signaling pathway triggered by GnIH is initiated by inhibiting adenylate cyclase and decreasing cAMP production in the target cell. GnIH neurons regulate not only gonadotropin synthesis and release in the pituitary, but also regulate various neurons in the brain, such as GnRH1, GnRH2, dopamine, POMC, NPY, orexin, MCH, CRH, oxytocin, and kisspeptin neurons. GnIH and GPR147 are also expressed in gonads and they may regulate steroidogenesis and germ cell maturation in an autocrine/paracrine manner. GnIH regulates reproductive development and activity. In female mammals, GnIH may regulate estrous or menstrual cycle. GnIH is also involved in the regulation of seasonal reproduction, but GnIH may finely tune reproductive activities in the breeding seasons. It is involved in stress responses not only in the brain but also in gonads. GnIH may inhibit male socio-sexual behavior by stimulating the activity of cytochrome P450 aromatase in the brain and stimulates feeding behavior by modulating the activities of hypothalamic and central amygdala neurons.

Matched MeSH terms: Neurons/metabolism
Differentiation of stem cells derived from carious teeth into dopaminergic-like cells

Gnanasegaran N, Govindasamy V, Abu Kasim NH

Int Endod J, 2016 Oct;49(10):937-49.
PMID: 26354006 DOI: 10.1111/iej.12545

AIM: To investigate whether dental pulp stem cells from carious teeth (DPSCs-CT) can differentiate into functional dopaminergic-like (DAergic) cells and provide an alternative cell source in regenerative medicine.
METHODOLOGY: Dental pulp stem cells from healthy (DPSCs) and carious teeth (DPSCs-CT) were isolated from young donors. Both cell lines were expanded in identical culture conditions and subsequently differentiated towards DAergic-like cells using pre-defined dopaminergic cocktails. The dopaminergic efficiencies were evaluated both at gene and protein as well as at secretome levels.
RESULTS: The efficiency of DPSCs-CT to differentiate into DAergic-like cells was not equivalent to that of DPSCs. This was further reflected in both gene and protein generation whereby key neuronal markers such as nestin, NURR1 and beta-III-tubulin were expressed significantly lower as compared to differentiated DPSCs (P

Matched MeSH terms: Dopaminergic Neurons/physiology*
ROCK2 inhibition: A futuristic approach for the management of Alzheimer's disease

Mani S, Jindal D, Chopra H, Jha SK, Singh SK, Ashraf GM, et al.

Neurosci Biobehav Rev, 2022 11;142:104871.
PMID: 36122738 DOI: 10.1016/j.neubiorev.2022.104871

Neurons depend on mitochondrial functions for membrane excitability, neurotransmission, and plasticity. Mitochondrial dynamics are important for neural cell maintenance. To maintain mitochondrial homeostasis, lysosomes remove dysfunctional mitochondria through mitophagy. Mitophagy promotes mitochondrial turnover and prevents the accumulation of dysfunctional mitochondria. In many neurodegenerative diseases (NDDs), including Alzheimer's disease (AD), mitophagy is disrupted in neurons. Mitophagy is regulated by several proteins; recently, Rho-associated coiled-coil containing protein kinase 2 (ROCK2) has been suggested to negatively regulate the Parkin-dependent mitophagy pathway. Thus, ROCK2 inhibition may be a promising therapy for NDDs. This review summarizes the mitophagy pathway, the role of ROCK2 in Parkin-dependent mitophagy regulation, and mitophagy impairment in the pathology of AD. We further discuss different ROCK inhibitors (synthetic drugs, natural compounds, and gene therapy-based approaches) and examine their effects on triggering neuronal growth and neuroprotection in AD and other NDDs. This comprehensive overview of the role of ROCK in mitophagy inhibition provides a possible explanation for the significance of ROCK inhibitors in the therapeutic management of AD and other NDDs.

Matched MeSH terms: Neurons/physiology
Plasma exosomes carrying mmu-miR-146a-5p and Notch signalling pathway-mediated synaptic activity in schizophrenia

Wang Z, Wu T, Hu H, Alabed AAA, Cui G, Sun L, et al.

J Psychiatry Neurosci, 2024;49(4):E265-E281.
PMID: 39209459 DOI: 10.1503/jpn.230118

BACKGROUND: Schizophrenia is characterized by a complex interplay of genetic and environmental factors, leading to alterations in various molecular pathways that may contribute to its pathogenesis. Recent studies have shown that exosomal microRNAs could play essential roles in various brain disorders; thus, we sought to explore the potential molecular mechanisms through which microRNAs in plasma exosomes are involved in schizophrenia.
METHODS: We obtained sequencing data sets (SUB12404730, SUB12422862, and SUB12421357) and transcriptome sequencing data sets (GSE111708, GSE108925, and GSE18981) from mouse models of schizophrenia using the Sequence Read Archive and the Gene Expression Omnibus databases, respectively. We performed differential expression analysis on mRNA to identify differentially expressed genes. We conducted Gene Ontology (GO) functional and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses to determine differentially expressed genes. Subsequently, we determined the intersection of differentially expressed microRNAs in plasma exosomes and in prefrontal cortex tissue. We retrieved downstream target genes of mmu-miR-146a-5p from TargetScan and used Cytoscape to visualize and map the microRNA-target gene regulatory network. We conducted in vivo experiments using MK-801-induced mouse schizophrenia models and in vitro experiments using cultured mouse neurons. The role of plasma exosomal miR-146a-5p in schizophrenia was validated using a cell counting kit, detection of lactate dehydrogenase, dual-luciferase assay, quantitative reverse transcription polymerase chain reaction, and Western blot analysis.
RESULTS: Differential genes were mainly enriched in synaptic regulation-related functions and pathways and were associated with neuronal degeneration. We found that mmu-miR-146a-5p was highly expressed in both prefrontal cortical tissue and plasma exosomes, which may be transferred to lobe cortical vertebral neurons, leading to the synergistic dysregulation of gene network functions and, therefore, promoting schizophrenia development. We found that mmu-miR-146a-5p may inhibit the Notch signalling pathway-mediated synaptic activity of mouse pyramidal neurons in the lobe cortex by targeting NOTCH1, which in turn could promote the onset and development of schizophrenia in mice.
LIMITATIONS: The study's findings are based on animal models and in vitro experiments, which may not fully replicate the complexity of human schizophrenia.
CONCLUSION: Our findings suggest that mmu-miR-146a-5p in plasma-derived exosomes may play an important role in the pathogenesis of schizophrenia. Our results provide new insights into the underlying molecular mechanisms of the disease.

Matched MeSH terms: Neurons/metabolism
Collateral projections from the lateral parabrachial nucleus to the bed nucleus of the stria terminalis and the central amygdala in mice

Zhang L, Zhou S, Tan YF, Gan QF, Koon TH, Wang Z, et al.

Neurosci Lett, 2025 Mar 28;853:138204.
PMID: 40113070 DOI: 10.1016/j.neulet.2025.138204

BACKGROUND: The lateral parabrachial nucleus (LPBn) serves a critical hub for processing and transmitting pain signals. It has two main efferent pathways, the LPBn-CeA and LPBn-BNST, which are crucial for pain regulation and the management of negative emotions.
METHODS: In our study, we investigated the projections from the LPBn by performing stereotaxic injections of AAV2/2Retro-hSyn-EGFP (abbreviated as EGFP) into the bed nucleus of the stria terminalis (BNST) and AAV2/2Retro-hSyn-tdTomato (abbreviated as tdTomato) into the central amygdala (CeA) in mice. The animals subsequently underwent spared nerve injury (SNI) surgery on the contralateral side to the AAV injections. To examine the expression of calcitonin gene-related peptide (CGRP) and c-Fos, we conducted immunofluorescent histochemistry.
RESULTS: Our results indicated that approximately 26 % of the LPBn neurons retrogradely labeled with either EGFP or tdTomato were dual-labeled with both markers. Moreover, a significant majority (85.49 %) of these double-labeled neurons were CGRP positive (CGRP+). In mice subjected to SNI, nearly all of these neurons (93.25 %) were c-Fos positive (c-Fos+), indicating that they were activated.
CONCLUSION: These findings suggest that a subset of CGRP+ neurons in the LPBn projects to both the BNST and CeA via axon collaterals. Notably, under SNI conditions, these neurons may play a critical role in the transmission of chronic pain.

Matched MeSH terms: Neurons/metabolism
Unraveling the role of glial cell line-derived neurotrophic factor in the treatment of Parkinson's disease

Kakoty V, Sarathlal KC, Kaur P, Wadhwa P, Vishwas S, Khan FR, et al.

Neurol Sci, 2024 Apr;45(4):1409-1418.
PMID: 38082050 DOI: 10.1007/s10072-023-07253-2

Parkinson's disease is the second most common neurodegenerative condition with its prevalence projected to 8.9 million individuals globally in the year 2019. Parkinson's disease affects both motor and certain non-motor functions of an individual. Numerous research has focused on the neuroprotective effect of the glial cell line-derived neurotrophic factor (GDNF) in Parkinson's disease. Discovered in 1993, GDNF is a neurotrophic factor identified from the glial cells which was found to have selective effects on promoting survival and regeneration of certain populations of neurons including the dopaminergic nigrostriatal pathway. Given this property, recent studies have focused on the exogenous administration of GDNF for relieving Parkinson's disease-related symptoms both at a pre-clinical and a clinical level. This review will focus on enumerating the molecular connection between Parkinson's disease and GDNF and shed light on all the available drug delivery approaches to facilitate the selective delivery of GDNF into the brain paving the way as a potential therapeutic candidate for Parkinson's disease in the future.

Matched MeSH terms: Neurons/metabolism

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links