Migratory patterns of clonally related cells in the developing central nervous system

Summary Neurons and glioblasts that arise in the ventricular zone migrate to form discrete nuclei and laminae as the central nervous system develops. By stably labeling precursor cells in the ventricular zone, pathways taken by different cells within an individual clone can be described. We have used recombinant retroviruses to label precursor cells with a heritable marker, theE. coli lacZ gene; clones of lacZ-positive cells are later mapped histochemically. Here we review results from three regions of the chicken central nervous system — the optic tectum, spinal cord, and forebrain - and compare them with previous results from mammalian cortex and other regions of the vertebrate CNS. In particular, we consider the relationship between migratory patterns and functional organization, the existence of multiple cellular sources of migratory guidance, and the issue of whether a cell's choice of migratory pathway influences its ultimate phenotype.     

Migratory patterns of clonally related cells in the developing central nervous system

Neurons and glioblasts that arise in the ventricular zone migrate to form discrete nuclei and laminae as the central nervous system develops. By stably labeling precursor cells in the ventricular zone, pathways taken by different cells within an individual clone can be described. We have used recombinant retroviruses to label precursor cells with a heritable marker, the E. coli lacZ gene; clones of lacZ-positive cells are later mapped histochemically. Here we review results from three regions of the chicken central nervous system--the optic tectum, spinal cord, and forebrain--and compare them with previous results from mammalian cortex and other regions of the vertebrate CNS. In particular, we consider the relationship between migratory patterns and functional organization, the existence of multiple cellular sources of migratory guidance, and the issue of whether a cell's choice of migratory pathway influences its ultimate phenotype.     

A central nervous system depressant-antidepressant.

A new tricyclic agent with an allenyl side chain experimentally shows antidepressant activity similar to amitriptyline and imipramine but also exerts marked CNS depression. Such dual activity should be of clinical interest for treatment of mixed anxiety and depression.     

Multitasking with neurotensin in the central nervous system

The 13-amino acid peptide neurotensin (NT) was discovered over 30 years ago and has been implicated in a wide variety of neurotransmitter and endocrine functions. This review focuses on four areas where there has been substantial recent progress in understanding NT signaling and several functions of the endogenous peptide. The first area concerns the functional activation of the high-affinity NT receptor, NTR-1, including the delineation of the NT binding pocket and receptor domains involved in functional coupling to intracellular signaling pathways. The development of NT receptor antagonists and the application of genetic and molecular genetic approaches have accelerated progress in understanding NT function in several areas, including the involvement of NT in antipsychotic drug actions, psychostimulant sensitization and the modulation of pain, and these are reviewed in that order. There is now substantial evidence indicating that NT is required for certain antipsychotic drug actions and that the peptide plays a key role in stress-induced analgesia.Received 18 March 2005; received after revision 9 May 2005; accepted 23 May 2005     

Heat shock response in the central nervous system

The heat shock response is induced in nervous tissue in a variety of clinically significant experimental models including ischemic brain injury (stroke), trauma, thermal stress and status epilepticus. Excessive excitatory neurotransmission or the inability to metabolically support normal levels of excitatory neurotransmission may contribute to neuronal death in the nervous system in many of the same pathophysiologic circumstances. We demonstrated that in vitro glutamate-neurotransmitter induced excitotoxicity is attenuated by the prior induction of the heat shock response. A short thermal stress induced a pattern of protein synthesis characteristic of the highly conserved heat shock response and increased the expression of heat shock protein (HSP) mRNA. Protein synthesis was necessary for the neuroprotective effect. The study of the mechanisms of heat shock mediated protection may lead to important clues as to the basic mechanisms underlying the molecular actions of the HSP and the factors important for excitotoxic neuronal injury. The clinical relevance of these findings in vitro is suggested by experiments performed by others in vivo demonstrating that pretreatment of animals with a submaximal thermal or ischemis stress confers protection from a subsequent ischemic insult.     

Axon guidance at the central nervous system midline

A key feature of the central nervous system of most higher organisms is their bilateral symmetry about the midline. The specialised cells that lie at the midline have an essential role in regulating the axon guidance decisions of both neurons that project axons across the midline and those that project on one side. The midline cells produce both attractive and repellent short- and long-range signals to guide axonal growth. The axons themselves express specific receptors that can be dynamically regulated in response to midline-derived signals. In this way, axons extend toward or away from the midline and those that do cross change their behaviour to respond to longitudinal signals on the contralateral side.     

Neuronal and glial markers of the central nervous system

Summary This brief review evaluates the expression of cell-specific markers on differentiated neural cells and, where necessary, on their developing precursors. Within these limitations only the commonly used markers are discussed and those deemed unequivocal are only briefly appraised.     

Neuronal and glial markers of the central nervous system

This brief review evaluates the expression of cell-specific markers on differentiated neural cells and, where necessary, on their developing precursors. Within these limitations only the commonly used markers are discussed and those deemed unequivocal are only briefly appraised.     

Neurotrophins and neuronal differentiation in the central nervous system

The central nervous system requires the proper formation of exquisitely precise circuits to function properly. These neuronal circuits are assembled during development by the formation of synaptic connections between hundreds of thousands of differentiating neurons. For these circuits to form correctly, neurons must elaborate precisely patterned axonal and dendritic arbors. Although the cellular and molecular mechanisms that guide neuronal differentiation and formation of connections remain mostly unknown, the neurotrophins have emerged recently as attractive candidates for regulating neuronal differentiation in the developing brain. The experiments reviewed here provide strong support for a bifunctional role for the neurotrophins in axonal and dendritic growth and are consistent with the exciting possibility that the neurotrophins might mediate activity-dependent synaptic plasticity.     

Relaxin family peptide systems and the central nervous system

Since its discovery in the 1920s, relaxin has enjoyed a reputation as a peptide hormone of pregnancy. However, relaxin and other relaxin family peptides are now associated with numerous non-reproductive physiologies and disease states. The new millennium bought with it the sequence of the human genome and subsequently new directions for relaxin research. In 2002, the ancestral relaxin gene RLN3 was identified from genome databases. The relaxin-3 peptide is highly expressed in a small region of the brain and in species from teleost to primates and has both conserved sequence and sites of expression. Combined with the discovery of the relaxin family peptide receptors, interest in the role of the relaxin family peptides in the central nervous system has been reignited. This review explores the relaxin family peptides that are expressed in or act upon the brain, the receptors that mediate their actions, and what is currently known of their functions.     

The role of apolipoprotein E in lipid metabolism in the central nervous system

The critical roles of apolipoprotein E (apoE) in regulating plasma lipid and lipoprotein levels have been extensively studied for over 2 decades. However, an understanding of the roles of apoE in the central nervous system (CNS) is less certain. This review will summarize the available experimental results on the role of apoE in CNS lipid homeostasis with respect to its modulation of sulfatide trafficking, alteration of CNS cholesterol homeostasis and apoE-induced changes in phospholipid molecular species in specialized subcellular membrane fractions. The results indicate that apoE mediates sulfatide trafficking and metabolism in the CNS. Moreover, although apoE does not affect the cholesterol mass content or the phospholipid mass levels and composition in the CNS as a whole, apoE modulates cholesterol and phospholipid homeostasis in selective subcellular membrane compartments. Through elucidating the roles of apoE in CNS lipid metabolism, new insights into overall functions of apoE in neurobiology can be accrued ultimately, leading to an increased understanding of CNS lipid metabolism and the identification of novel therapeutic targets for CNS diseases.Received 9 January 2004; received after revision 28 February 2004; accepted 10 March 2004     

Developmental and pathological angiogenesis in the central nervous system

Angiogenesis, the formation of new blood vessels from pre-existing vessels, in the central nervous system (CNS) is seen both as a normal physiological response as well as a pathological step in disease progression. Formation of the blood–brain barrier (BBB) is an essential step in physiological CNS angiogenesis. The BBB is regulated by a neurovascular unit (NVU) consisting of endothelial and perivascular cells as well as vascular astrocytes. The NVU plays a critical role in preventing entry of neurotoxic substances and regulation of blood flow in the CNS. In recent years, research on numerous acquired and hereditary disorders of the CNS has increasingly emphasized the role of angiogenesis in disease pathophysiology. Here, we discuss molecular mechanisms of CNS angiogenesis during embryogenesis as well as various pathological states including brain tumor formation, ischemic stroke, arteriovenous malformations, and neurodegenerative diseases.     

An antinicotinic action of papaverine in the central nervous system

Zusammenfassung Die Wirkungen von Papaverin auf die kortikale Aktivität des Präparates «encéphalé isolé» der Katzen wurden untersucht. Papaverin rief homogene kortikale Synchronisation für einige Minuten hervor und verminderte kortikale Nikotin-Desynchronisation für einige Stunden.     

The potential therapeutic role of statins in central nervous system autoimmune disorders

3-Hydroxy-3-methyglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins are widely used oral cholesterol-lowering drugs. Statins competitively inhibit HMG-CoA reductase, the enzyme that catalyzes conversion of HMG-CoA to L-mevalonate, a key intermediate in cholesterol synthesis. Certain metabolites of mevalonate are also involved in posttranslational modification of specific proteins involved in cell proliferation and differentiation. Thus, statins have important biologic effects that may be independent of their cholesterol-reducing properties. Recent studies indicate that statins have antiinflammatory and neuroprotective properties which may be beneficial in the treatment of multiple sclerosis as well as other central nervous system (CNS) neurodegenerative diseases. This article will outline current experimental evidence that may suggest potential clinical benefits for patients with CNS autoimmune disorders. Ultimately, clinical trials will have to determine the safety and efficacy of statins in this patient population.Received 17 April 2003; received after revision 21 May 2003; accepted 22 May 2003     

Visual responses in the central nervous system of the scallopPecten ziczac

Summary Electrical activity recorded from the lateral lobe of the visceroparietal ganglion in the scallop Pecten ziczac reflects predominatly the visual response to onset of light stimulation, suggesting that shadow reflex mechanisms likely occur elsewhere within the central nervous system.We thank Wolfgang Sterrer and the Bermude Biological Station for their cooperation and the use of their facilities. Support was, in part, from an NSF grant to the BBS (PCM 76.13459) and from an NIH grant (NS 12971). This paper is a contribution from the Bermuda Biological Station (No. 708) and the Tallahassee, Sopchoppy and Gulf Coast Marine Biological Association (No. 84).     

Binucleated neurons in the central nervous system of the laboratory animals

Summary Binucleated neurons were studied in the central nervous system of the rat and the rabbit. They were present in the young as well as the adult animals. The animals injected with thymidine-H³ during their embryonic development showed labelled binucleated neurons. It is suggested that the neurons become binucleated during neuroembryogenesis, and differentiate into normal neurons morphologically and physiologically.Supported by NIH Research grant No. NS-08817-05.