International Review of Neurobiology (INT REV NEUROBIOL)

Publications in this journal

• Article: Ethical aspects of neuromodulation.

  Christiane Woopen
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  ABSTRACT: Invasive and noninvasive technological neuromodulation of the brain has major impact on individual and social ethical issues like autonomy and justice. It also challenges the foundations of ethics itself by dealing with the preconditions of moral judgment and behavior. Ethical issues related to personal, clinical, and scientific integrity are addressed. Eight prevailing problems are identified with regard to anticipation, desperation, psychosocial impact, and authenticity, expansion of clinical application, enhancement, criterion of treatment resistance, and framework for research. It is argued for comprehensive multidisciplinary care during the treatment and adaptation process, for multifaceted data collection, and against a strict criterion of treatment resistance.
  International Review of Neurobiology 01/2012; 107:315-32.
• Article: Cyclin-dependent kinase 5 in axon growth and regeneration.

  Tao Ye, Amy K Y Fu, Nancy Y Ip
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  ABSTRACT: Injury to the central nervous system often leads to irreversible deficits because of the failure of damaged axons to regrow and restore the functional neural circuitry. Coordinated orchestration of multiple cellular processes including cytoskeletal dynamics and gene expression are essential for both developmental and regenerative axon growth. Recently, mounting evidence suggests that cyclin-dependent kinase 5 (Cdk5), a neuronal kinase implicated in almost all aspects of brain development and function, regulates multiple players required for axon formation and regeneration. Indeed, Cdk5 functions as a "plastic" kinase that maintains the axon growth ability by enabling efficient cytoskeletal reorganization, enhancing protein translation, reducing protein degradation, and promoting injury-induced gene transcription. Here, we summarize the up-to-date information on the mechanisms underlying the axon growth and regeneration after injury.
  International Review of Neurobiology 01/2012; 105:91-115.
• Article: Opportunities for bioinformatics in the classification of behavior and psychiatric disorders.

  Elissa J Chesler, Ryan W Logan
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  ABSTRACT: A bioinformatics approach to behavioral neuroscience provides both unique opportunities and challenges for research on behavior. A major challenge has been to describe, define, and discriminate among abstract behavioral processes, in large part by distinguishing among the biological mechanisms of unique but not entirely discrete, entities of behavior. Understanding the complexity of neurobiology and behavior requires integration of data across diverse biological systems, types of data, and levels of scale. With the perspective and application of bioinformatics, we can uncover the relationships among these systems and take steps forward in realizing the common and distinct bases of psychiatric disease.
  International Review of Neurobiology 01/2012; 104:183-211.
• Article: The function and mechanisms of Nurr1 action in midbrain dopaminergic neurons, from development and maintenance to survival.

  Yu Luo
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  ABSTRACT: Nurr1 is critical for the development and maintenance of midbrain dopaminergic (DA) neurons in mouse. Loss of Nurr1 function early during development in mice leads to the absence of midbrain DA neurons. Reduction of Nurr1 function in adulthood leads to a slowly progressive loss of striatal DA and markers for DAergic neurons, supporting its selective roles in the maintenance of DAergic neuronal survival and function. To understand the molecular mechanisms of Nurr1 action, our group has identified VIP as a potential target gene of Nurr1. Nurr1 regulates VIP mRNA and protein levels, and transactivates the VIP promoter through Nurr1-responsive cis elements. Nurr1 loss of function leads to the decrease of VIP mRNA level in developing midbrain, suggesting that Nurr1 is involved in the in vivo regulation of VIP expression in midbrain. Our group has also cloned a novel protein interactor for Nurr1. We identified a family of gene products that interact and regulate the activity of Nurr1 by screening yeast two-hybrid library and termed the longest splicing form, NuIP. In vivo NuIP protein is largely colocalized with Nurr1 in adult midbrain dopaminergic neurons. NuIP interacts and positively regulates the activity of Nurr1 protein and could also possibly mediate cross talk between Nurr1 and GTPase mediated signaling pathways. Other recently identified potential target genes and interacting proteins of Nurr1 are also summarized and discussed in this review.
  International Review of Neurobiology 01/2012; 102:1-22.
• Article: Alzheimer's disease and amyloid: culprit or coincidence?

  Stephen D Skaper
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  ABSTRACT: Alzheimer's disease (AD) is the largest unmet medical need in neurology today. This most common form of irreversible dementia is placing a considerable and increasing burden on patients, caregivers, and society, as more people live long enough to become affected. Current drugs improve symptoms but do not have profound neuroprotective and/or disease-modifying effects. AD is characterized by loss of neurons, dystrophic neurites, senile/amyloid/neuritic plaques, neurofibrillary tangles, and synaptic loss. Beta-amyloid (Aβ) peptide deposition is the major pathological feature of AD. Increasing evidence suggests that overexpression of the amyloid precursor protein and subsequent generation of the 39-43 amino acid residue, Aβ, are central to neuronal degeneration observed in AD patients possessing familial AD mutations, while transgenic mice overexpressing amyloid precursor protein develop AD-like pathology. Despite the genetic and cell biological evidence that supports the amyloid hypothesis, it is becoming increasing clear that AD etiology is complex and that Aβ alone is unable to account for all aspects of AD. The fact that vast overproduction of Aβ peptides in the brain of transgenic mouse models fails to cause overt neurodegeneration raises the question as to whether accumulation of Aβ peptides is indeed the culprit for neurodegeneration in AD. There is increasing evidence to suggest that Aβ/amyloid-independent factors, including the actions of AD-related genes (microtubule-associated protein tau, polymorphisms of apolipoprotein E4), inflammation, and oxidative stress, also contribute to AD pathogenesis. This chapter reviews the current state of knowledge on these factors and their possible interactions, as well as their potential for neuroprotection targets.
  International Review of Neurobiology 01/2012; 102:277-316.
• Article: Environmental conditions modulate neurotoxic effects of psychomotor stimulant drugs of abuse.

  Eugene A Kiyatkin, Hari Shanker Sharma
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  ABSTRACT: Psychomotor stimulants such as methamphetamine (METH), amphetamine, and 3,4-metylenedioxymethamphetamine (MDMA or ecstasy) are potent addictive drugs. While it is known that their abuse could result in adverse health complications, including neurotoxicity, both the environmental conditions and activity states associated with their intake could strongly enhance drug toxicity, often resulting in life-threatening health complications. In this review, we analyze results of animal experiments that suggest that even moderate increases in environmental temperatures and physiological activation, the conditions typical of human raves parties, dramatically potentiate brain hyperthermic effects of METH and MDMA. We demonstrate that METH also induces breakdown of the blood-brain barrier, acute glial activation, brain edema, and structural abnormalities of various subtypes of brain cells; these effects are also strongly enhanced when the drug is used at moderately warm environmental conditions. We consider the mechanisms underlying environmental modulation of acute drug neurotoxicity and focus on the role of brain temperature, a critical homeostatic parameter that could be affected by metabolism-enhancing drugs and environmental conditions and affect neural activity and functions.
  International Review of Neurobiology 01/2012; 102:147-71.
• Article: Cross species integration of functional genomics experiments.

  Jeremy J Jay
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  ABSTRACT: There is an increasing recognition of the value in integrating behavioral genomics data across species. The fragmentation of public resources, interoperability, and available representations present challenges due to the array of identifiers used to represent each genome feature. Once data are organized into a coherent collection, they can be integrated using a variety of methods to analyze convergent evidence for the roles of genes in behaviors. GeneWeaver.org is a web-based software system that employs many of these techniques and has been used in the study of complex behavior and addiction. These techniques will be increasingly necessary to understand global patterns emerging from experiments in behavioral genomics.
  International Review of Neurobiology 01/2012; 104:1-24.
• Article: From bench to beside to cure spinal cord injury: lost in translation?

  Andreas Hug, Norbert Weidner
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  ABSTRACT: Despite intense efforts to overcome the inhospitable milieu for axonal regeneration within the damaged spinal cord an evidence-based repair strategy promoting relevant functional improvement is still not available for spinal cord injured individuals. Nevertheless, several preclinical axonal regenerative strategies were developed all the way to phase I/II clinical trials, which have recently been terminated. The aim of this chapter is to critically review translated preclinical treatment strategies with respect to their conformity with previously published guidelines and requirements for preclinical studies leading to clinical trials in human subjects with spinal cord injury (SCI). Cell-based strategies (macrophage and embryonic stem cell grafting) and the administration of C3 transferase inhibitors and anti-Nogo-A antibodies were investigated. Overall, these four approaches comply with preclinical quality standards to varying degree. For future preclinical analyses, several additive components such as defined criteria for robustness of observed effects, a clear confirmation of underlying structural mechanisms, and the implementation of appropriate preclinical rehab approaches should be considered in order to increase the quality and consequently the likelihood of respective therapeutic strategies to succeed in human individuals suffering from SCI.
  International Review of Neurobiology 01/2012; 106:173-96.
• Article: DBS and Electrical Neuro-Network Modulation to Treat Neurological Disorders.

  Amanda Thompson, Takashi Morishita, Michael S Okun
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  ABSTRACT: The use of neuromodulatory techniques in the treatment of neurological disorders is expanding and now includes devices targeting the motor cortex, basal ganglia, spinal cord, peripheral nervous system, and autonomic nervous system. In this chapter, we review and discuss the current and past literature as well as review indications for each of these devices in the ongoing management of many common neurological diseases including chronic pain, Parkinson's disease, tremor, dystonia, and epilepsy. We also discuss and update mechanisms of deep brain stimulation and electrical neuro-network modulation.
  International Review of Neurobiology 01/2012; 107:253-82.
• Article: Gatekeeper Between Quiescence and Differentiation: p53 in Axonal Outgrowth and Neurogenesis.

  Giorgia Quadrato, Simone Di Giovanni
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  ABSTRACT: The transcription factor and tumor suppressor gene p53 regulates a wide range of cellular processes including DNA damage/repair, cell cycle progression, apoptosis, and cell metabolism. In the past several years, a specific novel role for p53 in neuronal biology has emerged. p53 orchestrates the polarity of self-renewing divisions in neural stem cells both during embryonic development and in adulthood and coordinates the timing for cell fate specification. In postmitotic neurons, p53 regulates neurite outgrowth and postinjury axonal regeneration via neurotrophin-dependent and -independent signaling by both transcriptional and posttranslational control of growth cone remodeling. This review provides an insight into the molecular mechanisms upstream and downstream p53 both during neural development and following axonal injury. Their understanding may provide therapeutic targets to enhance neuroregeneration following nervous system injury.
  International Review of Neurobiology 01/2012; 105:71-89.
• Article: The role of serotonin in axon and dendrite growth.

  Ephraim F Trakhtenberg, Jeffrey L Goldberg
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  ABSTRACT: The neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) plays multiple roles in the enteric, peripheral, and central nervous systems (CNS). Although its most prominent biological function is as a signal transmission messenger from pre- to postsynaptic neurons, other roles such as shaping brain development and regulating neurite growth have also been described. Here, we review the less well-studied role of 5-HT as a modulator of neurite growth. 5-HT has been shown to regulate neurite growth in multiple systems and species, including in the mammalian CNS. 5-HT predominantly appears to suppress neurite growth, but depending on the model system and 5-HT receptor subtype, in rare cases, it may promote neurite outgrowth and elongation. Failure of axon regeneration in the adult mammalian CNS is a major problem in multiple diseases, and understanding how 5-HT receptors signal opposing effects on neurite growth may lead to novel neuroregenerative therapies, by targeting either 5-HT receptors or their downstream signaling pathways.
  International Review of Neurobiology 01/2012; 106:105-26.
• Article: Current challenges to the clinical translation of brain machine interface technology.

  Charles W Lu, Parag G Patil, Cynthia A Chestek
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  ABSTRACT: Development of neural prostheses over the past few decades has produced a number of clinically relevant brain-machine interfaces (BMIs), such as the cochlear prostheses and deep brain stimulators. Current research pursues the restoration of communication or motor function to individuals with neurological disorders. Efforts in the field, such as the BrainGate trials, have already demonstrated that such interfaces can enable humans to effectively control external devices with neural signals. However, a number of significant issues regarding BMI performance, device capabilities, and surgery must be resolved before clinical use of BMI technology can become widespread. This chapter reviews challenges to clinical translation and discusses potential solutions that have been reported in recent literature, with focuses on hardware reliability, state-of-the-art decoding algorithms, and surgical considerations during implantation.
  International Review of Neurobiology 01/2012; 107:137-60.
• Article: Large-scale neuroinformatics for in situ hybridization data in the mouse brain.

  Lydia L Ng, Susan M Sunkin, David Feng, Chris Lau, Chinh Dang, Michael J Hawrylycz
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  ABSTRACT: Large-scale databases of the brain are providing content to the neuroscience community through molecular, cellular, functional, and connectomic data. Organization, presentation, and maintenance requirements are substantial given the complexity, diverse modalities, resolution, and scale. In addition to microarrays, magnetic resonance imaging, and RNA sequencing, several in situ hybridization databases have been constructed due to their value in spatially localizing cellular expression. Scalable techniques for processing and presenting these data for maximum utility in viewing and analysis are key for end user value. We describe methods and use cases for the Allen Brain Atlas resources of the adult and developing mouse.
  International Review of Neurobiology 01/2012; 104:159-82.
• Article: Text-mining and neuroscience.

  Kyle H Ambert, Aaron M Cohen
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  ABSTRACT: The wealth and diversity of neuroscience research are inherent characteristics of the discipline that can give rise to some complications. As the field continues to expand, we generate a great deal of data about all aspects, and from multiple perspectives, of the brain, its chemistry, biology, and how these affect behavior. The vast majority of research scientists cannot afford to spend their time combing the literature to find every article related to their research, nor do they wish to spend time adjusting their neuroanatomical vocabulary to communicate with other subdomains in the neurosciences. As such, there has been a recent increase in the amount of informatics research devoted to developing digital resources for neuroscience research. Neuroinformatics is concerned with the development of computational tools to further our understanding of the brain and to make sense of the vast amount of information that neuroscientists generate (French & Pavlidis, 2007). Many of these tools are related to the use of textual data. Here, we review some of the recent developments for better using the vast amount of textual information generated in neuroscience research and publication and suggest several use cases that will demonstrate how bench neuroscientists can take advantage of the resources that are available.
  International Review of Neurobiology 01/2012; 103:109-32.
• Article: Computational models of neuromodulation.

  Christopher R Butson
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  ABSTRACT: As neuromodulation therapy has grown, so has the recognition that computational models can provide important insights into the design, operation, and clinical application of neurostimulation systems. Models of deep brain stimulation and spinal cord stimulation have advanced over recent decades from simple, stereotyped models to sophisticated patient-specific models that can incorporate many important details of the stimulation system and the attributes of individual subjects. Models have been used to make detailed predictions of the bioelectric fields produced during stimulation. These predictions have been used as a starting point for further analyses such as stimulation safety, neural response, neurostimulation system design, or clinical outcomes. This chapter provides a review of recent advances and anticipated future directions in computational modeling of neuromodulation.
  International Review of Neurobiology 01/2012; 107:5-22.
• Article: Neuromodulation in psychiatric disorders.

  Yasin Temel, Sarah A Hescham, Ali Jahanshahi, Marcus L F Janssen, Sonny K H Tan, Jacobus J van Overbeeke, Linda Ackermans, Mayke Oosterloo, Annelien Duits, Albert F G Leentjens, Leewei Lim
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  ABSTRACT: Psychiatric disorders are worldwide a common cause of severe and long-term disability and socioeconomic burden. The management of patients with psychiatric disorders consists of drug therapy and/or psychotherapy. However, in some patients, these treatment modalities do not produce sufficient therapeutic effects or induce intolerable side effects. For these patients, neuromodulation has been suggested as a potential treatment modality. Neuromodulation includes deep brain stimulation, vagal nerve stimulation, and transcranial magnetic and electrical stimulation. The rationale for neuromodulation is derived from the research identifying neurobiologically localized substrates for refractory psychiatric symptoms. Here, we review the clinical data on neuromodulation in the major psychiatric disorders. Relevant data from animal models will also be discussed to explain the neurobiological basis of the therapy.
  International Review of Neurobiology 01/2012; 107:283-314.
• Article: The neurobehavior ontology: an ontology for annotation and integration of behavior and behavioral phenotypes.

  Georgios V Gkoutos, Paul N Schofield, Robert Hoehndorf
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  ABSTRACT: In recent years, considerable advances have been made toward our understanding of the genetic architecture of behavior and the physical, mental, and environmental influences that underpin behavioral processes. The provision of a method for recording behavior-related phenomena is necessary to enable integrative and comparative analyses of data and knowledge about behavior. The neurobehavior ontology facilitates the systematic representation of behavior and behavioral phenotypes, thereby improving the unification and integration behavioral data in neuroscience research.
  International Review of Neurobiology 01/2012; 103:69-87.
• Article: Molecular control of axon growth: insights from comparative gene profiling and high-throughput screening.

  Murray G Blackmore
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  ABSTRACT: Axon regeneration in the mammalian adult central nervous system (CNS) is limited by an intrinsically low capacity for axon growth in many CNS neurons. In contrast, embryonic, peripheral, and many nonmammalian neurons are capable of successful regeneration. Numerous studies have compared mammalian CNS neurons to their counterparts in regenerating systems in an effort to identify candidate genes that control regenerative ability. This review summarizes work using this comparative strategy and examines our current understanding of gene function in axon growth, highlighting the emergence of genome-wide expression profiling and high-throughput screening strategies to identify novel regulators of axon growth.
  International Review of Neurobiology 01/2012; 105:39-70.
• Article: Nanotechnology in neuromodulation.

  Russell J Andrews
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  ABSTRACT: As clinical neuromodulation moves beyond electrical stimulation with macroelectrodes, the need becomes apparent for techniques that interact with the nervous system on its own level (neurons and glia) and using its own mechanisms (electrical and chemical). To communicate in a manner that corrects nervous system disorders (rather than merely masking them) requires techniques at the micron to submicron (cellular and possibly intracellular) level. Substituting appropriately configured carbon nanoelectrodes for platinum macroelectrodes affords orders of magnitude improvement in both charge transfer (stimulation) and charge detection (recording). Nanoelectrodes offer the ability to monitor, simultaneously, several neurotransmitters in real time as well as electrical activity. To take full advantage of the possibilities of micron-level nanoarrays for neuromodulation, two techniques will need to be incorporated: (1) computational modeling of both nervous system electrical and chemical activity and (2) minimally invasive access to all regions of the nervous system.
  International Review of Neurobiology 01/2012; 107:161-84.