Molecular Neurobiology (MOL NEUROBIOL )

Publisher: Humana Press, Springer Verlag

Description

As one of the premier review journals in the neurosciences, Molecular Neurobiology is specifically designed to synthesize and critically assess research trends in experimental and clinical neuroscience at the molecular level. Its distinguished editorial board is comprised of four Nobelists and other preeminent neuroscientists who carefully review papers to ensure their high quality.

  • Impact factor
    5.47
  • 5-year impact
    5.54
  • Cited half-life
    5.70
  • Immediacy index
    0.78
  • Eigenfactor
    0.01
  • Article influence
    1.80
  • Website
    Molecular Neurobiology website
  • Other titles
    Molecular neurobiology
  • ISSN
    1559-1182
  • OCLC
    15640289
  • Material type
    Periodical, Internet resource
  • Document type
    Journal / Magazine / Newspaper, Internet Resource

Publisher details

Springer Verlag

  • Pre-print
    • Author can archive a pre-print version
  • Post-print
    • Author can archive a post-print version
  • Conditions
    • Authors own final version only can be archived
    • Publisher's version/PDF cannot be used
    • On author's website or institutional repository
    • On funders designated website/repository after 12 months at the funders request or as a result of legal obligation
    • Published source must be acknowledged
    • Must link to publisher version
    • Set phrase to accompany link to published version (The original publication is available at www.springerlink.com)
    • Articles in some journals can be made Open Access on payment of additional charge
  • Classification
    ​ green

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract T-2 toxin is the most toxic trichothecene and a frequent contaminant in many agriculture products. Dietary ingestion represents the most common route of T-2 toxin exposure in humans. T-2 toxin exposure leads to many pathological conditions like nervous disorders, cardiovascular alterations, immune depression and dermal inflammation. However, the neuronal toxicity of T-2 toxin in vitro remains unclear. In the present study, we investigated the mechanism of T-2 toxin-induced apoptosis in human neuroblastoma cells (IMR-32). T-2 toxin was cytotoxic at a low concentration of 10 ng/ml. The 50 % inhibitory concentration (IC50) of T-2 toxin was found to be 40 ng/ml as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay, crystal violet dye exclusion test and lactate dehydrogenase (LDH) leakage. T-2 toxin increased intracellular reactive oxygen species generation as early as 15 min and peaked at 60 min as analyzed by flow cytometry. Annexin V+propidium iodide staining showed time-dependent increase in percent apoptotic c e l l s . DNA gel electrophoresis showed oligonucleosomal DNA fragmentation typical of apoptotic cells. Additionally, casapse-3 activation and PARP cleavage indicated involvement of mitochondrial mediated caspase-dependent pathway of apoptosis. Cell cycle analysis revealed time-dependent increase in sub-G1 population of cells and significant up-regulation of CDK2, CDK6, cyclin A and p21 messenger RNA (mRNA) levels. Exposure to T-2 toxin induced the phosphorylation of extracellular signal-regulated kinase (ERK), p38-mitogenactivated protein kinase and c-jun N-terminal kinases (JNK). Analysis of human phospho-mitogen-activated protein kinase (MAPK) antibody array revealed timedependent increase in phosphorylation. Upstream of ERK pathway Grb2, Ras and Raf and downstream transcription factors c-fos and c-jun were significantly up-regulated. ZVAD- FMK and MAPK inhibitors (PD 98059, SB 203580 and ZM 336372) exposure prior to T-2 toxin treatment significantly decreased percent of apoptotic cells compared to only T-2 toxin-exposed cells. Results of the present study show that T-2 toxin at nanogram concentrations can induce apoptosis in human neuronal cells through multiple signal transduction pathways. The study provides possible leads for developing therapeutic approaches to prevent T-2 toxin-induced neurotoxicity.
    Molecular Neurobiology 08/2014;
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    ABSTRACT: Small molecule histone deacetylase inhibitors (HDIs) hold much promise as pharmacological modifiers of the epigenetic status of the central nervous system (CNS), given their ability to cross the blood-brain barrier. This is particularly relevant given the lack of disease-modifying therapies for many neurodegenerative diseases and that epigenetic perturbations are increasingly recognised as playing a key role in their pathophysiology. In particular, emerging evidence in recent years has shown that epigenetic dysregulation may contribute to dopaminergic neuronal death in Parkinson's disease. As a result, a number of pan-HDIs have been explored as potential neuroprotective agents for dopaminergic neurons. However, it is not known if the neuroprotective effects of pan-histone deacetylase (HDAC) inhibition are a general phenomenon or if these effects require inhibition of specific classes of HDACs. Here, we examine the ability of class-specific HDIs to promote neurite growth in a variety of cellular contexts. We find that MC1568, a class IIa-specific HDI, promotes neurite growth and arbourisation and protects neurite arbours against neurotoxic insult. Furthermore, we show that class IIa-specific HDAC inhibition results in activation of the canonical Smad signalling pathway, which is known to promote the survival and growth of midbrain dopaminergic neurons. These results demonstrate the potential of class IIa-specific HDIs as regulators of neuronal structure and suggest they should be examined in animal models of Parkinson's disease as the next stage in rationalising their use as a potential therapy for this disorder.
    Molecular Neurobiology 07/2014;
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    ABSTRACT: We have published extensively on the neurogenetics of brain reward systems with reference to the genes related to dopaminergic function in particular. In 1996, we coined “Reward Deficiency Syndrome” (RDS), to portray behaviors found to have gene-based association with hypodopaminergic function. RDS as a useful concept has been embraced in many subsequent studies, to increase our understanding of Substance Use Disorder (SUD), addictions, and other obsessive, compulsive, and impulsive behaviors. Interestingly, albeit others, in one published study, we were able to describe lifetime RDS behaviors in a recovering addict (17 years sober) blindly by assessing resultant Genetic Addiction Risk Score (GARS™) data only. We hypothesize that genetic testing at an early age may be an effective preventive strategy to reduce or eliminate pathological substance and behavioral seeking activity. Here, we consider a select number of genes, their polymorphisms, and associated risks for RDS whereby, utilizing GWAS, there is evidence for convergence to reward candidate genes. The evidence presented serves as a plausible brain-print providing relevant genetic information that will reinforce targeted therapies, to improve recovery and prevent relapse on an individualized basis. The primary driver of RDS is a hypodopaminergic trait (genes) as well as epigenetic states (methylation and deacetylation on chromatin structure). We now have entered a new era in addiction medicine that embraces the neuroscience of addiction and RDS as a pathological condition in brain reward circuitry that calls for appropriate evidence-based therapy and early genetic diagnosis and that requires further intensive investigation.
    Molecular Neurobiology 05/2014;
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    ABSTRACT: Parkinson's disease (PD) is pathologically characterized by selective loss of dopaminergic neurons in the midbrain and the existence of intracellular protein inclusions termed Lewy bodies, largely composed of α-synuclein. Genetic studies have revealed that rare point mutations in the gene encoding α-synuclein including A30P, A53T, and E46K are associated with familial forms of PD, indicating a pathological role for mutant α-synuclein in PD etiology. However, the mechanisms underlying the neuronal toxicity of mutant α-synuclein are still to be elucidated. Growing evidence has suggested a deleterious effect of mutant α-synuclein on the autophagy-lysosome pathway. In this study, we discovered that overexpression of human E46K mutant α-synuclein impaired macroautophagy in mammalian cells. Our data showed that overexpression of E46K mutant α-synuclein impaired autophagy at an early stage of autophagosome formation via the c-Jun N-terminal kinase 1 (JNK1)-Bcl-2 but not the mammalian target of rapamycin (mTOR) pathway. Overexpressed E46K mutant α-synuclein inhibited JNK1 activation, leading to a reduced Bcl-2 phosphorylation and increased association between Bcl-2 and Beclin1, further disrupting the formation of Beclin1/hVps34 complex, which is essential for autophagy initiation. Furthermore, overexpression of E46K mutant α-synuclein increased the vulnerability of differentiated PC12 cells to rotenone treatment, which would be partly due to its inhibitory effects on autophagy. Our findings may shed light on the potential roles of mutant α-synuclein in the pathogenesis of PD.
    Molecular Neurobiology 05/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Information generated from animal models, genome sequencing, and high-throughput technologies provide valuable sequence of events to understand the Parkinson's disease (PD) pathogenesis. A dynamic equilibrium between biosynthesis and biodegradation of sub-cellular components by ubiquitin proteasome system and autophagy is found to be responsible for sustaining the homeostasis of tyrosine hydroxylase-positive neurons. Autophagy degrades and eliminates α-synuclein, Parkin, ubiquitin, etc., proteins along with damaged cellular components to maintain the homeostasis of the nigrostriatal dopaminergic neurons. Aberrant type II apoptosis is widely implicated in dopaminergic neurodegeneration leading to PD. The current article reviews the elementary role of autophagy in the degradation and elimination of superfluous and aggregated proteins and impaired mitochondria. The article also recapitulates the information, which implicated the role of aberrant autophagy in toxin-induced Parkinsonism. Moreover, the review sheds light on whether or not targeting the defective autophagy could reinstate the normal functioning of dopaminergic neurons, which could ultimately rescue from PD pathogenesis.
    Molecular Neurobiology 05/2014;
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    ABSTRACT: The macrophage migration inhibitory factor (MIF) is a multifaceted cytokine involved in many processes, including cellular responses to ischemia/reperfusion injury in the heart and brain. This study was undertaken to determine whether human MIF expression is induced following cerebral ischemia and its role therein. To examine whether the induction of MIF gene expression was mediated by its transcriptional upregulation, the human MIF gene promoter was cloned and a luciferase assay was used to determine the presence of a hypoxia-responsive region in the human MIF promoter. We found that human MIF promoter activity was significantly upregulated by hypoxia. A functional hypoxia-inducible factor 1α-binding site was identified using an electrophoretic mobility shift assay (EMSA). MIF has a protective effect on cortical neurons under oxygen-glucose deprivation (OGD) treatment. MIF significantly reduced OGD-induced cell death. To determine whether the expression of MIF in the human brain is altered following ischemia, brain sections from 10 stroke patients were examined with an antibody against MIF. Blood vessel endothelial cells in the peri-infarct region of ischemic brain displayed strong MIF immunoreactivity with no MIF immunoreactivity in control brains. Furthermore, we found that treatment of human brain endothelial cells with MIF had no effect on human monocyte adhesion to endothelium. Our study demonstrates that MIF gene expression is altered during stroke and dysregulation of the hypoxia signaling-induced MIF expression plays an important role in neuronal death in stroke.
    Molecular Neurobiology 05/2014;
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    ABSTRACT: There is compelling evidence that sleep deprivation (SD) is an effective strategy in promoting antidepressant effects in humans, whereas few studies were performed in relevant animal models of depression. Acute administration of antidepressants in humans and rats generates a quite similar effect, i.e., suppression of rapid eye movement (REM) sleep. Then, we decided to investigate the neurochemical alterations generated by a protocol of rapid eye movement sleep deprivation (REMSD) in the notably known animal model of depression induced by the bilateral olfactory bulbectomy (OBX). REMSD triggered antidepressant mechanisms such as the increment of brain-derived neurotrophic factor (BDNF) levels, within the substantia nigra pars compacta (SNpc), which were strongly correlated to the swimming time (r = 0.83; P < 0.0001) and hippocampal serotonin (5-HT) content (r = 0.66; P = 0.004). Moreover, there was a strong correlation between swimming time and hippocampal 5-HT levels (r = 0.70; P = 0.003), strengthen the notion of an antidepressant effect associated to REMSD in the OBX rats. In addition, REMSD robustly attenuated the hippocampal 5-HT deficiency produced by the OBX procedure. Regarding the rebound (REB) period, we observed the occurrence of a sustained antidepressant effect, indicated mainly by the swimming and climbing times which could be explained by the maintenance of the increased nigral BDNF expression. Hence, hippocampal 5-HT levels remained enhanced in the OBX group after this period. We suggested that the neurochemical complexity inflicted by the OBX model, counteracted by REMSD, is directly correlated to the nigral BDNF expression and hippocampal 5-HT levels. The present findings provide new information regarding the antidepressant mechanisms triggered by REMSD.
    Molecular Neurobiology 05/2014;
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    ABSTRACT: The eye is a special sensory organ, which is basically an extension of the brain. Both are derived from neural tube and consist of neurons. Therefore, diseases of both the brain and eye should have some similarity. Neurodegenerative disorders like Alzheimer's disease (AD) is the major cause of dementia in the world. Amyloid deposition in the cerebral cortex and hippocampal region is the basic pathology in AD. But along with it, there are various changes that take place in the eye, i.e., abnormal pupillary reaction, decreased vision, decreased contrast sensitivity, visual field changes, loss of retinal ganglionic cells and retinal fiber layer, peripapillary atrophy, increased cup-disk ratio, retinal thinning, tortuosity of blood vessels, and deposition of Aβ-like substance in the retina. And these changes are present in the early part of the disease when only mild cognitive impairment is there. As the brain is covered by a hard bony skull which makes it difficult to directly visualize the changes occurring in the brain at molecular levels, finer details of disease progression are not available with us. But the eye is the window of the brain; with advanced modern techniques, we can directly visualize the changes in the retina at a very fine level. Therefore, by depicting neurodegenerative changes in the eye, we can diagnose and manage AD at very early stages. Along with it, retinal neurodegenerations like glaucoma and age-related macular degeneration (ARMD) are the major cause of loss of vision, and still, there are no effective treatment modalities for these blinding conditions. So if we can understand its pathogenesis and progression by correlating with brain neurodegenerations, we can come up with a better therapy for glaucoma and ARMD.
    Molecular Neurobiology 05/2014;
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    ABSTRACT: Diabetic retinopathy (DR) was earlier recognized as a vascular disease, but nowadays, it is considered as a neurovascular disorder. Neuronal death is the primary change which leads to various vascular changes which are visible to an ophthalmologist. But these changes are feature of an advanced disease and can affect vision at any moment of time. There are various evidences which suggests that glutamate excitotoxicity, hyperhomocysteinemia, kynurenic acid, and erythro-poietin plays important role in causation of retinal ganglionic cell apoptosis in diabetic patients. Adaptive optics, a new imaging technique, also showed that loss of photoreceptors (specialized neurons) is the early change in diabetic retinopathy. These changes suggest DR as a neurovascular disorder. Neuroprotective agents also showed good results in delaying progression of DR especially memantine, insulin receptor activation, and neurotrophic factors. More research in this field will help us to find novel therapeutic measures for DR, which can delay or even stop progression of DR at a very early stage.
    Molecular Neurobiology 05/2014;
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    ABSTRACT: Accumulating evidence suggests that ischemic preconditioning (IPC) increases cerebral tolerance to the subsequent ischemic exposure. However, the underlying mechanisms are still not fully understood. In the present study, we tested the hypothesis that AMP-activated protein kinase (AMPK)-dependent autophagy contributed to the neuroprotection of IPC in rats with permanent cerebral ischemia. Male Sprague-Dawley rats were pretreated with vehicle, compound C (an AMPK inhibitor), or 3-methyladenine (3-MA, an autophagy inhibitor) and then were subjected to IPC induced by a 10-min middle cerebral artery occlusion. Afterward, the brain AMPK activity and autophagy biomarkers were measured. At 24 h after IPC, permanent cerebral ischemia was induced in these rats, and infarct volume, neurological deficits as well as cell apoptosis were evaluated 24 h later. We demonstrated that IPC activated AMPK and induced autophagy in the brain, which was accompanied by a reduction of infract volume, neurological deficits, and cell apoptosis after cerebral ischemia. Meanwhile, the IPC-induced autophagy was inhibited by compound C while the neuroprotection of IPC was abolished by compound C or 3-MA. These findings suggest that AMPK-mediated autophagy contributes to the neuroprotection of IPC, highlighting AMPK as a therapeutic target for stroke prevention and treatment.
    Molecular Neurobiology 05/2014;
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    ABSTRACT: Motor neuron disorders, and particularly amyotrophic lateral sclerosis (ALS), are fatal diseases that are due to the loss of motor neurons in the brain and spinal cord, with progressive paralysis and premature death. It has been recently shown that the most frequent genetic cause of ALS, frontotemporal dementia (FTD), and other neurological diseases is the expansion of a hexanucleotide repeat (GGGGCC) in the non-coding region of the C9ORF72 gene. The pathogenic mechanisms that produce cell death in the presence of this expansion are still unclear. One of the most likely hypotheses seems to be the gain-of-function that is achieved through the production of toxic RNA (able to sequester RNA-binding protein) and/or toxic proteins. In recent works, different authors have reported that antisense oligonucleotides complementary to the C9ORF72 RNA transcript sequence were able to significantly reduce RNA foci generated by the expanded RNA, in affected cells. Here, we summarize the recent findings that support the idea that the buildup of "toxic" RNA containing the GGGGCC repeat contributes to the death of motor neurons in ALS and also suggest that the use of antisense oligonucleotides targeting this transcript is a promising strategy for treating ALS/frontotemporal lobe dementia (FTLD) patients with the C9ORF72 repeat expansion. These data are particularly important, given the state of the art antisense technology, and they allow researchers to believe that a clinical application of these discoveries will be possible soon.
    Molecular Neurobiology 05/2014;
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    ABSTRACT: Stressful stimuli can exacerbate persistent pain disorder. However, the underlying mechanism is still unknown. Here, to reveal the underlying mechanism for stressful stimuli-induced hyperalgesia in chronic pain, we investigated the effect of extracellular signal-regulated kinase1/2 (ERK1/2) activation on pain hypersensitivity using single-prolonged stress (SPS) model, complete Freund's adjuvant (CFA) model and SPS + CFA model. The experimental results revealed significantly reduced paw withdrawal threshold in the SPS, CFA, and SPS + CFA group compared with the control group. However, the increased phosphorylation of ERK1/2 in the medial prefrontal cortex (mPFC) was observed in the SPS- or SPS + CFA-exposed group but not the CFA group compared with control group. There was also a significant increase in mPFC ERK1/2 phosphorylation and mechanical allodynia after SPS + CFA treatment compared to SPS or CFA treatment alone. Furthermore, inhibiting ERK1/2 phosphorylation by microinjection of U0126, a MAPK kinase (MEK) inhibitor, into the mPFC attenuated SPS + CFA- and SPS- but not CFA-induced mechanical allodynia, anxiety-like behavior, and cognitive impairments. These results suggest that the activation of ERK1/2 in the mPFC may contribute to the process of stress-induced cognitive and emotional disorders, leading to an increase in pain sensitivity.
    Molecular Neurobiology 05/2014;

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