Cells of the Central Nervous System: An Overview of Their Structure and Function.

The central nervous system is the last major organ system in the vertebrate body to yield its cellular structure, due to the complexity of its cells and their interactions. The fundamental unit of the nervous system is the neuron, which forms complex circuits that receive and integrate information and generate adaptive responses. Each neuron is composed of an input domain consisting of multiple dendrites along with the cell body, which is also responsible for the majority of macromolecule synthesis for the cell.

Formulated Curcumin Prevents Paclitaxel-Induced Peripheral Neuropathy through Reduction in Neuroinflammation by Modulation of α7 Nicotinic Acetylcholine Receptors.

Paclitaxel is widely used in the treatment of various types of solid malignancies. Paclitaxel-induced peripheral neuropathy (PIPN) is often characterized by burning pain, cold, and mechanical allodynia in patients. Currently, specific pharmacological treatments against PIPN are lacking.

Impact of Dose, Sex, and Strain on Oxaliplatin-Induced Peripheral Neuropathy in Mice.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common, dose limiting, and long-lasting side effect of chemotherapy treatment. Unfortunately, no treatment has proven efficacious for this side effect. Rodent models play a crucial role in the discovery of new mechanisms underlying the initiation, progression, and recovery of CIPN and the potential discovery of new therapeutics.

A Fenofibrate Diet Prevents Paclitaxel-Induced Peripheral Neuropathy in Mice.

Background: Paclitaxel-induced peripheral neuropathy (PIPN) is a major adverse effect of this chemotherapeutic agent that is used in the treatment of a number of solid malignancies. PIPN leads notably to burning pain, cold and mechanical allodynia. PIPN is thought to be a consequence of alterations of mitochondrial function, hyperexcitability of neurons, nerve fiber loss, oxidative stress and neuroinflammation in dorsal root ganglia (DRG) and spinal cord (SC).

Potential Neurodevelopmental Effects of Pediatric Intensive Care Sedation and Analgesia: Repetitive Benzodiazepine and Opioid Exposure Alters Expression of Glial and Synaptic Proteins in Juvenile Rats.

Unlabelled: Sedatives are suspected contributors to neurologic dysfunction in PICU patients, to whom they are administered during sensitive neurodevelopment. Relevant preclinical modeling has largely used comparatively brief anesthesia in infant age-approximate animals, with insufficient study of repetitive combined drug administration during childhood. We hypothesized that childhood neurodevelopment is selectively vulnerable to repeated treatment with benzodiazepine and opioid.

Endogenous opioid peptides and brain development: Endomorphin-1 and Nociceptin play a sex-specific role in the control of oligodendrocyte maturation and brain myelination.

The generation of fully functional oligodendrocytes, the myelinating cells of the central nervous system, is preceded by a complex maturational process. We previously showed that the timing of oligodendrocyte differentiation and rat brain myelination were altered by perinatal exposure to buprenorphine and methadone, opioid analogs used for the management of pregnant addicts. Those observations suggested the involvement of the μ-opioid receptor (MOR) and the nociceptin/orphanin FQ receptor (NOR).

The α7 nicotinic receptor silent agonist R-47 prevents and reverses paclitaxel-induced peripheral neuropathy in mice without tolerance or altering nicotine reward and withdrawal.

Various antitumor drugs, including paclitaxel, frequently cause chemotherapy-induced peripheral neuropathy (CIPN) that can be sustained even after therapy has been completed. The current work was designed to evaluate R-47, an α7 nAChR silent agonist, in our mouse model of CIPN. R-47 was administered to male C57BL/6J mice prior to and during paclitaxel treatment.

Lack of paclitaxel effects on intracranial self-stimulation in male and female rats: comparison to mechanical sensitivity.

Paclitaxel is a cancer chemotherapy with adverse effects that include peripheral neuropathy, neuropathic pain, and depression of behavior and mood. In rodents, hypersensitive paw-withdrawal reflexes from mechanical stimuli serve as one common measure of paclitaxel-induced pain-related behavior. This study tested the hypothesis that paclitaxel would also depress rates of positively reinforced operant responding as a measure of pain-related behavioral depression.

Nicotine Prevents and Reverses Paclitaxel-Induced Mechanical Allodynia in a Mouse Model of CIPN.

Chemotherapy-induced peripheral neuropathy (CIPN), a consequence of peripheral nerve fiber dysfunction or degeneration, continues to be a dose-limiting and debilitating side effect during and/or after cancer chemotherapy. Paclitaxel, a taxane commonly used to treat breast, lung, and ovarian cancers, causes CIPN in 59-78% of cancer patients. Novel interventions are needed due to the current lack of effective CIPN treatments.

Novel role of the nociceptin system as a regulator of glutamate transporter expression in developing astrocytes.

Our previous results showed that oligodendrocyte development is regulated by both nociceptin and its G-protein coupled receptor, the nociceptin/orphanin FQ receptor (NOR). The present in vitro and in vivo findings show that nociceptin plays a crucial conserved role regulating the levels of the glutamate/aspartate transporter GLAST/EAAT1 in both human and rodent brain astrocytes. This nociceptin-mediated response takes place during a critical developmental window that coincides with the early stages of astrocyte maturation.

Effects of paclitaxel on the development of neuropathy and affective behaviors in the mouse.

Paclitaxel, one of the most commonly used cancer chemotherapeutic drugs, effectively extends the progression-free survival of breast, lung, and ovarian cancer patients. However, paclitaxel and other chemotherapy drugs elicit peripheral nerve fiber dysfunction or degeneration that leads to peripheral neuropathy in a large proportion of cancer patients. Patients receiving chemotherapy also often experience changes in mood, including anxiety and depression.

The opioid system and brain development: effects of methadone on the oligodendrocyte lineage and the early stages of myelination.

Oligodendrocytes express opioid receptors throughout development, but the role of the opioid system in myelination remains poorly understood. This is a significant problem as opioid use and abuse continue to increase in two particular populations: pregnant addicts (in whom drug effects could target early myelination in the fetus and newborn) and adolescents and young adults (in whom late myelination of 'higher-order' regions takes place). Maintenance treatments for opioid addicts include the long-lasting opioids methadone and buprenorphine.

The incorporation of growth factor and chondroitinase ABC into an electrospun scaffold to promote axon regrowth following spinal cord injury.

Spinal cord injury results in tissue necrosis in and around the lesion site, commonly leading to the formation of a fluid-filled cyst. This pathological end point represents a physical gap that impedes axonal regeneration. To overcome the obstacle of the cavity, we have explored the extent to which axonal substrates can be bioengineered through electrospinning, a process that uses an electrical field to produce fine fibres of synthetic or biological molecules.

Two pole air gap electrospinning: Fabrication of highly aligned, three-dimensional scaffolds for nerve reconstruction.

We describe the structural and functional properties of three-dimensional (3D) nerve guides fabricated from poly-ε-caprolactone (PCL) using the air gap electrospinning process. This process makes it possible to deposit nano-to-micron diameter fibers into linear bundles that are aligned in parallel with the long axis of a cylindrical construct. By varying starting electrospinning conditions it is possible to modulate scaffold material properties and void space volume.

Evaluating neuronal and glial growth on electrospun polarized matrices: bridging the gap in percussive spinal cord injuries.

One of the many obstacles to spinal cord repair following trauma is the formation of a cyst that impedes axonal regeneration. Accordingly, we examined the potential use of electrospinning to engineer an implantable polarized matrix for axonal guidance. Polydioxanone, a resorbable material, was electrospun to fabricate matrices possessing either aligned or randomly oriented fibers.

Opioid addiction and pregnancy: perinatal exposure to buprenorphine affects myelination in the developing brain.

Buprenorphine is a mu-opioid receptor partial agonist and kappa-opioid receptor antagonist currently on trials for the management of pregnant opioid-dependent addicts. However, little is known about the effects of buprenorphine on brain development. Oligodendrocytes express opioid receptors in a developmentally regulated manner and thus, it is logical to hypothesize that perinatal exposure to buprenorphine could affect myelination.

The adhesive role of acetylcholinesterase (AChE): detection of AChE binding proteins in developing rat spinal cord.

Acetylcholinesterase (AChE) is expressed by dorsal root ganglion (DRG) neurons during developmental periods when their central axons are growing into and through the spinal cord. Importantly, our previous studies have shown that AChE induces DRG axonal outgrowth by an adhesive mechanism and thus, have now employed a blot overlay technique to screen for potential AChE binding proteins in the developing spinal cord. Our results show that: (1) AChE binds to proteins with apparent molecular weights of 200, 110, 35, and 33 kDa; (2) these proteins are developmentally expressed during periods of axonal outgrowth from DRG neurons; (3) all four proteins are synthesized by astrocytes; and (4) AChE binding to these proteins is highly dependent on ionic strength supporting an electrostatic mechanism of adhesion.

Differential transactivation of sphingosine-1-phosphate receptors modulates NGF-induced neurite extension.

The process of neurite extension after activation of the TrkA tyrosine kinase receptor by nerve growth factor (NGF) involves complex signaling pathways. Stimulation of sphingosine kinase 1 (SphK1), the enzyme that phosphorylates sphingosine to form sphingosine-1-phosphate (S1P), is part of the functional TrkA signaling repertoire. In this paper, we report that in PC12 cells and dorsal root ganglion neurons, NGF translocates SphK1 to the plasma membrane and differentially activates the S1P receptors S1P1 and S1P2 in a SphK1-dependent manner, as determined with specific inhibitors and small interfering RNA targeted to SphK1.

The mammalian amiloride-insensitive non-specific salt taste receptor is a vanilloid receptor-1 variant.

The amiloride-insensitive salt taste receptor is the predominant transducer of salt taste in some mammalian species, including humans. The physiological, pharmacological and biochemical properties of the amiloride-insensitive salt taste receptor were investigated by RT-PCR, by the measurement of unilateral apical Na+ fluxes in polarized rat fungiform taste receptor cells and by chorda tympani taste nerve recordings. The chorda tympani responses to NaCl, KCl, NH4Cl and CaCl2 were recorded in Sprague-Dawley rats, and in wild-type and vanilloid receptor-1 (VR-1) knockout mice.