Lorne M. Mendell | |
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| Citizenship | United States |
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| Known for | Neurotophins and neuroplasticity |
| Spouse(s) | Nancy Mendell, Ph.D. |
| Children | 2 |
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Lorne Mendell is a neurobiologist currently employed as a distinguished professor in the department of neurobiology and behavior at Stony Brook University in New York. [1] His research focuses primarily on neurotrophins in neonatal and adult mammals, and on the neuroplasticity of the mammalian spinal cord. His research interests lie in other areas including pain, nerve wind-up, and specifically the neurotrophin NT-3. He has contributed to the growing pool of knowledge of axonal development and regeneration of immature and mature neurons. He has been a part of the search for novel treatments for spinal cord injuries and continues to study neurotrophins to determine their effects on neuronal plasticity. He served a term as president of the Society of Neuroscience during 1997–1998.
Mendell graduated from McGill University in 1961 with a Bachelor of Science in both mathematics and physics. He earned his Ph.D. in neurophysiology from the Massachusetts Institute of Technology in 1965. He is married to Nancy Mendell, a professor emerita in the department of applied mathematics and statistics at Stony Brook University. They have a son and a daughter. [2]
Shortly after earning his Ph.D., Mendell became a faculty member at Duke University Medical Center in 1968. He remained at Duke until 1980 when he joined the faculty at Stony Brook University. Since then, Mendell has held numerous positions in a number of associations and organizations. He has also received many honors and awards throughout his career as a neurobiologist. [1]
Mendell's research within neurotrophins has focused specifically on nerve growth factors (NGF) and their role that they play within inflammatory pain. [3] Within this, there was also a focus in brain-derived neurotrophic factor (BDNF) and their sensitizing effect on specific synaptic transmission between nociceptors and their target. [4] In his recent labs, he has been studying the contributions of a third neurotrophin (NT-3) and the effects of altering the synapses involved in transmission between stretch receptors and motor neurons.
Mendell's research on neuronal plasticity is specifically focused on the mammalian spinal cord. He has combined some of his research from NT-3 to help show how neurotrophins can help alter the function of both damaged and undamaged neurons.
Much of the work Mendell has done with both neurotrophin and neuronal plasticity has some overlap into the realm of pain, and what their roles are in both reducing and relieving pain. For example, Mendell has conducted research which has shown the relationship between nerve growth factors and inflammatory pain.
Mendell discovered the property of windup pain in the spinal cord. Windup is the property of C-fibres in the peripheral nerves of the spinal cord that when stimulated at repetitious low frequencies there will be a gradual accumulation in the amplitude of response. [5]
Mendell has been interested in the role neurotrophins play in nervous plasticity since at least the mid-1990s. At the time, neurotrophins were understood to be significant factors in neuronal development and differentiation in the central and peripheral nervous system, however; scientists were still exploring the specific functions of individual neurotrophins. Subsequent findings suggested that neurotrophins have effects on both damaged and undamaged neurons. As such, neurotrophins are a major facet of spinal cord injury research. Mendell's research on neurotrophins has evolved synchronously with the understanding of neurotrophins. In more recent times, Mendell's research has been focused partly on spinal cord injury and the use of neurotophins as a possible treatment. [6]
Hyperalgesia, increase of sensitivity to a stimulus, was found by Mendell to be influenced by the introduction of nerve growth factor (NGF). It functions by interactions with sensory nociceptive neurons. Mendell was able to investigate how rodents and mammals sensitivity to thermal and mechanical stimulus was increased through exposure to NGF. [7] NGF was shown by Mendell to also play a role in the development of young mammals. Mature animals, he showed, that NGF had a possible role in the linkage of hyperalgesia and inflammation. [8]
In 1965, Mendell's doctoral dissertation was published in the academic journal Nature . His dissertation focused on neuronal fibers in the spinal cord and their effect on other fibers, specifically how C fibers in the dorsal horn of the spinal cord affect A fibers. Mendell's research did not support the conclusion that the activation of C fibers did not have an effect on the A fibers in question.
Mendell contributed to a 2016 publication that focused on the relationship between a protein called CD2AP and the plasticity of neurons. [6] It is known that the growth of an axon of a neuron helps with both the adaptive and maladaptive plasticity within the nervous system. Therefore, if an axon becomes injured, or cannot function to its best ability, the consequences can be in the form of neurologic disease. The protein CD2AP in this study was looked at in depth, which is responsible for coordinating axon outgrowth. Mendell and his team were able to observe that CD2AP is amplified within dorsal root ganglions (DRGs) during axonal sprouting, but decreases in quantity during axonal regeneration. Based on these findings, it is still undetermined what the exact relationship between the control of the regeneration of previously damaged axons and the additional development of non-damaged axons is.
Mendell was also involved in a 2011 study, that explored the mechanisms involved in the relationship between neuronal growth factors (NGF) and pain. [9] The NGF-TrkA axis, can facilitate the development of many different types of long-term acute and chronic pain. Specific mutations in NGF or TrkA genes can lead to a decrease in the sensitivity to pain. This study suggested an important relationship between the pain and the number of NGF-responsive (TrkA-positive) nociceptors connected to the tissue where the pain is coming from. This relationship has important implications in the treatment of chronic pain. With this relationship in mind, the pain can be targeted by more specific treatment.
Mendell has also put forth research about the increased possibility of promoting spinal cord repair through a combination of several different treatments. [10] The mechanisms involved in this are due to the additive effects when several different neurotrophins and proteins are combined, including chondroitinase ABC, NT3, and enhanced levels of NR2D. These together allow for either the synthesis or strengthening of spinal circuits, as well as slight recovery of function for those that have been damaged.
An axon or nerve fiber is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action potentials away from the nerve cell body. The function of the axon is to transmit information to different neurons, muscles, and glands. In certain sensory neurons, such as those for touch and warmth, the axons are called afferent nerve fibers and the electrical impulse travels along these from the periphery to the cell body and from the cell body to the spinal cord along another branch of the same axon. Axon dysfunction can be the cause of many inherited and acquired neurological disorders that affect both the peripheral and central neurons. Nerve fibers are classed into three types – group A nerve fibers, group B nerve fibers, and group C nerve fibers. Groups A and B are myelinated, and group C are unmyelinated. These groups include both sensory fibers and motor fibers. Another classification groups only the sensory fibers as Type I, Type II, Type III, and Type IV.
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes that impact the body, then works in tandem with the endocrine system to respond to such events. Nervous tissue first arose in wormlike organisms about 550 to 600 million years ago. In vertebrates, it consists of two main parts, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS consists of the brain and spinal cord. The PNS consists mainly of nerves, which are enclosed bundles of the long fibers, or axons, that connect the CNS to every other part of the body. Nerves that transmit signals from the brain are called motor nerves or efferent nerves, while those nerves that transmit information from the body to the CNS are called sensory nerves or afferent. Spinal nerves are mixed nerves that serve both functions. The PNS is divided into three separate subsystems, the somatic, autonomic, and enteric nervous systems. Somatic nerves mediate voluntary movement. The autonomic nervous system is further subdivided into the sympathetic and the parasympathetic nervous systems. The sympathetic nervous system is activated in cases of emergencies to mobilize energy, while the parasympathetic nervous system is activated when organisms are in a relaxed state. The enteric nervous system functions to control the gastrointestinal system. Both autonomic and enteric nervous systems function involuntarily. Nerves that exit from the cranium are called cranial nerves while those exiting from the spinal cord are called spinal nerves.
The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field of neural development draws on both neuroscience and developmental biology to describe and provide insight into the cellular and molecular mechanisms by which complex nervous systems develop, from nematodes and fruit flies to mammals.
A nociceptor is a sensory neuron that responds to damaging or potentially damaging stimuli by sending "possible threat" signals to the spinal cord and the brain. The brain creates the sensation of pain to direct attention to the body part, so the threat can be mitigated; this process is called nociception.
Brain-derived neurotrophic factor (BDNF), or abrineurin, is a protein that, in humans, is encoded by the BDNF gene. BDNF is a member of the neurotrophin family of growth factors, which are related to the canonical nerve growth factor (NGF), a family which also includes NT-3 and NT-4/NT-5. Neurotrophic factors are found in the brain and the periphery. BDNF was first isolated from a pig brain in 1982 by Yves-Alain Barde and Hans Thoenen.
Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.
Astrogliosis is an abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system (CNS) trauma, infection, ischemia, stroke, autoimmune responses or neurodegenerative disease. In healthy neural tissue, astrocytes play critical roles in energy provision, regulation of blood flow, homeostasis of extracellular fluid, homeostasis of ions and transmitters, regulation of synapse function and synaptic remodeling. Astrogliosis changes the molecular expression and morphology of astrocytes, in response to infection for example, in severe cases causing glial scar formation that may inhibit axon regeneration.
In cellular neuroscience, the soma, perikaryon, neurocyton, or cell body is the bulbous, non-process portion of a neuron or other brain cell type, containing the cell nucleus. Although it is often used to refer to neurons, it can also refer to other cell types as well, including astrocytes, oligodendrocytes, and microglia. There are many different specialized types of neurons, and their sizes vary from as small as about 5 micrometres to over 10 millimetres for some of the smallest and largest neurons of invertebrates, respectively.
Nerve growth factor (NGF) is a neurotrophic factor and neuropeptide primarily involved in the regulation of growth, maintenance, proliferation, and survival of certain target neurons. It is perhaps the prototypical growth factor, in that it was one of the first to be described. Since it was first isolated by Nobel Laureates Rita Levi-Montalcini and Stanley Cohen in 1956, numerous biological processes involving NGF have been identified, two of them being the survival of pancreatic beta cells and the regulation of the immune system.
Tropomyosin receptor kinase A (TrkA), also known as high affinity nerve growth factor receptor, neurotrophic tyrosine kinase receptor type 1, or TRK1-transforming tyrosine kinase protein is a protein that in humans is encoded by the NTRK1 gene.
Tropomyosin receptor kinase B (TrkB), also known as tyrosine receptor kinase B, or BDNF/NT-3 growth factors receptor or neurotrophic tyrosine kinase, receptor, type 2 is a protein that in humans is encoded by the NTRK2 gene. TrkB is a receptor for brain-derived neurotrophic factor (BDNF). The standard pronunciation for this protein is "track bee".
The p75 neurotrophin receptor (p75NTR) was first identified in 1973 as the low-affinity nerve growth factor receptor (LNGFR) before discovery that p75NTR bound other neurotrophins equally well as nerve growth factor. p75NTR is a neurotrophic factor receptor. Neurotrophic factor receptors bind Neurotrophins including Nerve growth factor, Neurotrophin-3, Brain-derived neurotrophic factor, and Neurotrophin-4. All neurotrophins bind to p75NTR. This also includes the immature pro-neurotrophin forms. Neurotrophic factor receptors, including p75NTR, are responsible for ensuring a proper density to target ratio of developing neurons, refining broader maps in development into precise connections. p75NTR is involved in pathways that promote neuronal survival and neuronal death.
Neurotrophic factors (NTFs) are a family of biomolecules – nearly all of which are peptides or small proteins – that support the growth, survival, and differentiation of both developing and mature neurons. Most NTFs exert their trophic effects on neurons by signaling through tyrosine kinases, usually a receptor tyrosine kinase. In the mature nervous system, they promote neuronal survival, induce synaptic plasticity, and modulate the formation of long-term memories. Neurotrophic factors also promote the initial growth and development of neurons in the central nervous system and peripheral nervous system, and they are capable of regrowing damaged neurons in test tubes and animal models. Some neurotrophic factors are also released by the target tissue in order to guide the growth of developing axons. Most neurotrophic factors belong to one of three families: (1) neurotrophins, (2) glial cell-line derived neurotrophic factor family ligands (GFLs), and (3) neuropoietic cytokines. Each family has its own distinct cell signaling mechanisms, although the cellular responses elicited often do overlap.
Nerve injury is an injury to a nerve. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve fiber injury and whether there is continuity of the nerve. Usually, however, nerve injuries are classified in five stages, based on the extent of damage to both the nerve and the surrounding connective tissue, since supporting glial cells may be involved.
Group C nerve fibers are one of three classes of nerve fiber in the central nervous system (CNS) and peripheral nervous system (PNS). The C group fibers are unmyelinated and have a small diameter and low conduction velocity, whereas Groups A and B are myelinated. Group C fibers include postganglionic fibers in the autonomic nervous system (ANS), and nerve fibers at the dorsal roots. These fibers carry sensory information.
Trk receptors are a family of tyrosine kinases that regulates synaptic strength and plasticity in the mammalian nervous system. Trk receptors affect neuronal survival and differentiation through several signaling cascades. However, the activation of these receptors also has significant effects on functional properties of neurons.
The axon reflex is the response stimulated by peripheral nerves of the body that travels away from the nerve cell body and branches to stimulate target organs. Reflexes are single reactions that respond to a stimulus making up the building blocks of the overall signaling in the body's nervous system. Neurons are the excitable cells that process and transmit these reflex signals through their axons, dendrites, and cell bodies. Axons directly facilitate intercellular communication projecting from the neuronal cell body to other neurons, local muscle tissue, glands and arterioles. In the axon reflex, signaling starts in the middle of the axon at the stimulation site and transmits signals directly to the effector organ skipping both an integration center and a chemical synapse present in the spinal cord reflex. The impulse is limited to a single bifurcated axon, or a neuron whose axon branches into two divisions and does not cause a general response to surrounding tissue.
Neurotrophic factor receptors or neurotrophin receptors are a group of growth factor receptors which specifically bind to neurotrophins.
A Campenot chamber is a three-chamber petri dish culture system devised by Robert Campenot to study neurons. Commonly used in neurobiology, the neuron soma or cell body is physically compartmentalized from its axons allowing for spatial segregation during investigation. This separation, typically done with a fluid impermeable barrier, can be used to study nerve growth factors (NGF). Neurons are particularly sensitive to environmental cues such as temperature, pH, and oxygen concentration which can affect their behavior.
Sandra M. Garraway is a Canadian-American neuroscientist and assistant professor of physiology in the Department of Physiology at Emory University School of Medicine in Atlanta, Georgia. Garraway is the director of the Emory Multiplex Immunoassay Core (EMIC) where she assists researchers from both academia and industry to perform, analyze, and interpret their multiplexed immunoassays. Garraway studies the neural mechanisms of spinal nociceptive pain after spinal cord injury and as a postdoctoral researcher she discovered roles for both BDNF and ERK2 in pain sensitization and developed novel siRNA technology to inhibit ERK2 as a treatment for pain.
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