Locus ceruleus
Encyclopedia
The locus coeruleus is a nucleus in the brainstem involved with physiological
responses to stress
and panic
. It was discovered in the 18th century by Félix Vicq-d'Azyr
.
The locus coeruleus is the principal site for brain synthesis of norepinephrine
(noradrenaline). The locus coeruleus and the areas of the body affected by the norepinephrine it produces are described collectively as the locus coeruleus-noradrenergic system or LC-NA system. Norepinephrine may also be released directly into the blood from the adrenal medulla
.
The name is derived from the Latin words coeruleus and locus. Literally, this means "the blue spot", a name derived from its azure appearance in unstained brain tissue. The color is due to light scattering from melanin
in noradrenergic (producing or activated by norepinephrine) nerve cell bodies. Caeruleus is the classical Latin spelling, but coeruleus is the more common spelling. The spelling ceruleus, formed by contraction of the digraph ae or oe into e, is an American English form.
in the lateral floor of the fourth ventricle
. It is composed of mostly medium-size neurons. Melanin granules inside the neurons of the LC contribute to its blue color. Thus, it is also known as the nucleus pigmentosus pontis, meaning "heavily pigmented nucleus of the pons." The neuromelanin is formed by the polymerization
of noradrenaline and is analogous to the black dopamine
-based neuromelanin in the substantia nigra
.
In adult humans (19-78) the locus coeruleus has 22,000 to 51,000 total pigmented neurons that range in size between 31,000 to 60, 000 μm3.
, the brain stem, cerebellum
, hypothalamus
, the thalamic relay nuclei
, the amygdala
, the basal telencephalon
, and the cortex
. The norepinephrine from the LC has an excitatory effect on most of the brain, mediating arousal and priming the brain’s neurons to be activated by stimuli.
As an important homeostatic
control center of the body, the locus coeruleus receives afferents from the hypothalamus. The cingulate gyrus and the amygdala also innervate the LC, allowing emotional pain and stressors to trigger noradrenergic responses. The cerebellum and afferents from the raphe nuclei
also project to the LC, particularly the raphe pontis and raphe dorsalis.
The locus coeruleus receives inputs from a number of other brain regions, primarily:
, panic disorder
, and anxiety
. Some medications including norepinephrine reuptake inhibitor
s (reboxetine
, atomoxetine), serotonin-norepinephrine reuptake inhibitor
s (venlafaxine
), and norepinephrine-dopamine reuptake inhibitor
s (bupropion
) are believed to show efficacy by acting upon neuron
s in this area. This area of the brain is also intimately involved in REM sleep.
Psychiatric research has documented that enhanced noradrenergic postsynaptic responsiveness in the neuronal pathway (brain circuit) that originates in the locus coeruleus and end in the basolateral nucleus of the amygdala is a major factor in the pathophysiology of most stress-induced fear-circuitry disorders and especially in posttraumatic stress disorder (PTSD). The LC neurons are probably the origin of the first or second “leg” of what has been recently termed the "PTSD candidate circuit." Combat-related PTSD (in a 2005 study of deceased American army veterans from World War II) was shown to be associated with a postmortem diminished number of neurons in the locus coeruleus (LC) on the right side of the brain. The role of the LC in PTSD may explain the dramatic effectiveness of two generic medications, propranolol and prazosin
for the secondary prevention and treatment of PTSD, respectively.
), activate the hypothalamic-pituitary-adrenal axis
, and increase the sympathetic discharge/inhibit parasympathetic tone (through the brainstem). Specific to the activation of the hypothalamo-pituitary adrenal axis, norepinephrine will stimulate the secretion of corticotropin-releasing factor from the hypothalamus, which induces adrenocorticotropic hormone
release from the anterior pituitary
and subsequent cortisol synthesis in the adrenal glands. Norepinephrine released from locus coeruleus will feedback to inhibit its production, and corticotropin-releasing hormone will feedback to inhibit its production, while positively feeding to the locus coeruleus to increase norepinephrine production.
The LC's role in cognitive function in relation to stress is complex and multi-modal. Norepinephrine released from the LC can act on α2 receptors to increase working memory, or an excess of NE may decrease working memory by binding to the lower affinity α1 receptors.
s inhibit the firing of neurons in the locus coeruleus. When opioid consumption is stopped, the increased activity of the locus coeruleus contributes to the symptoms of opiate withdrawal. The alpha2 adrenoceptor agonist clonidine
is used to counteract this withdrawal effect by decreasing adrenergic neurotransmission from the locus coeruleus.
is responsible for Rett syndrome
. A MECP2 deficiency has been associated to catecholaminergic dysfunctions related to autonomic and sympathoadrenergic system in mouse models of Rett Syndrome (RTT). The Locus Coeruleus is the major source of noradrenergic innervation in the brain and sends widespread connections to rostral (cerebral cortex, hippocampus, hypothalamus) and caudal (cerebellum, brainstem nuclei) brain areas and. Indeed, an alteration of this structure could contribute to several symptoms observed in MECP2-deficient mice. Changes in the electrophysiological properties of cells in the locus ceruleus
were shown. These Locus Coeruleus cell changes include hyperexcitability and decreased functioning of its noradrenergic innervation. Interestingly, a reduction of the tyrosine hydroxylase (TH) mRNA level, the rate-limiting enzyme in catecholamine synthesis, was detected in the whole pons of MECP2-null male as well as in adult heterozygous female mice. Using immunoquantification techniques, a decrease of TH protein staining level, number of locus coeruleus TH-expressing neurons and density of dendritic arborization surrounding the structure was shown in symptomatic MECP2-deficient mice. However, locus coeruleus cells are not dying but are more likely losing their fully mature phenotype since no apoptotic neurons in the pons were detected. Researchers have concluded that "Because these neurons are a pivotal source of norepinephrine throughout the brainstem and forebrain and are involved in the regulation of diverse functions disrupted in Rett Syndrome, such as respiration and cognition, we hypothesize that the locus ceruleus is a critical site at which loss of MECP2 results in CNS dysfunction. Restoration of normal locus ceruleus function may therefore be of potential therapeutic value in the treatment of Rett Syndrome. This could explain why a norepinephrine reuptake inhibitor (desipramine, DMI) which enhances the extracellular NE levels at all noradrenergic synapses ameliorated some Rett syndrome symptoms in a mouse model of Rett syndrome.
. Mouse models of Alzheimer's disease show accelerated progression after chemical destruction of the locus ceruleus The norepinephrine from locus ceruleus cells in addition to its neurotransmitter role locally defuses from "varicosities". As such it provides an endogenous antiinflammatory agent in the microenvironment around the neurons, glial cell
s, and blood vessels in the neocortex and hippocampus. It has been shown that norepinephrine stimulates mouse microglia to suppress Aβ-induced production of cytokine
s and their phagocytosis of Aβ. This suggests that degeneration of the locus ceruleus might be responsible for increased Aβ deposition in AD brains.
Physiology
Physiology is the science of the function of living systems. This includes how organisms, organ systems, organs, cells, and bio-molecules carry out the chemical or physical functions that exist in a living system. The highest honor awarded in physiology is the Nobel Prize in Physiology or...
responses to stress
Stress (medicine)
Stress is a term in psychology and biology, borrowed from physics and engineering and first used in the biological context in the 1930s, which has in more recent decades become commonly used in popular parlance...
and panic
Panic
Panic is a sudden sensation of fear which is so strong as to dominate or prevent reason and logical thinking, replacing it with overwhelming feelings of anxiety and frantic agitation consistent with an animalistic fight-or-flight reaction...
. It was discovered in the 18th century by Félix Vicq-d'Azyr
Félix Vicq-d'Azyr
Félix Vicq d'Azyr was a French physician and anatomist, the originator of comparative anatomy and discoverer of the theory of homology in biology.-Biography:Vicq d'Azyr was born in Valognes, Normandy, the son of a physician...
.
The locus coeruleus is the principal site for brain synthesis of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(noradrenaline). The locus coeruleus and the areas of the body affected by the norepinephrine it produces are described collectively as the locus coeruleus-noradrenergic system or LC-NA system. Norepinephrine may also be released directly into the blood from the adrenal medulla
Adrenal medulla
The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. It is the innermost part of the adrenal gland, consisting of cells that secrete epinephrine , norepinephrine , and a small amount of dopamine in response to...
.
The name is derived from the Latin words coeruleus and locus. Literally, this means "the blue spot", a name derived from its azure appearance in unstained brain tissue. The color is due to light scattering from melanin
Melanin
Melanin is a pigment that is ubiquitous in nature, being found in most organisms . In animals melanin pigments are derivatives of the amino acid tyrosine. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms...
in noradrenergic (producing or activated by norepinephrine) nerve cell bodies. Caeruleus is the classical Latin spelling, but coeruleus is the more common spelling. The spelling ceruleus, formed by contraction of the digraph ae or oe into e, is an American English form.
Anatomy
The locus coeruleus (or "LC") is in the dorsal wall of the rostral ponsPons
The pons is a structure located on the brain stem, named after the Latin word for "bridge" or the 16th-century Italian anatomist and surgeon Costanzo Varolio . It is superior to the medulla oblongata, inferior to the midbrain, and ventral to the cerebellum. In humans and other bipeds this means it...
in the lateral floor of the fourth ventricle
Fourth ventricle
The fourth ventricle is one of the four connected fluid-filled cavities within the human brain. These cavities, known collectively as the ventricular system, consist of the left and right lateral ventricles, the third ventricle, and the fourth ventricle...
. It is composed of mostly medium-size neurons. Melanin granules inside the neurons of the LC contribute to its blue color. Thus, it is also known as the nucleus pigmentosus pontis, meaning "heavily pigmented nucleus of the pons." The neuromelanin is formed by the polymerization
Polymerization
In polymer chemistry, polymerization is a process of reacting monomer molecules together in a chemical reaction to form three-dimensional networks or polymer chains...
of noradrenaline and is analogous to the black dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
-based neuromelanin in the substantia nigra
Substantia nigra
The substantia nigra is a brain structure located in the mesencephalon that plays an important role in reward, addiction, and movement. Substantia nigra is Latin for "black substance", as parts of the substantia nigra appear darker than neighboring areas due to high levels of melanin in...
.
In adult humans (19-78) the locus coeruleus has 22,000 to 51,000 total pigmented neurons that range in size between 31,000 to 60, 000 μm3.
Connections
The projections of this nucleus reach far and wide. For example, they innervate the spinal cordSpinal cord
The spinal cord is a long, thin, tubular bundle of nervous tissue and support cells that extends from the brain . The brain and spinal cord together make up the central nervous system...
, the brain stem, cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
, hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
, the thalamic relay nuclei
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, the amygdala
Amygdala
The ' are almond-shaped groups of nuclei located deep within the medial temporal lobes of the brain in complex vertebrates, including humans. Shown in research to perform a primary role in the processing and memory of emotional reactions, the amygdalae are considered part of the limbic system.-...
, the basal telencephalon
Telencephalon
The cerebrum or telencephalon, together with the diencephalon, constitutes the forebrain. The cerebrum is the most anterior region of the vertebrate central nervous system. Telencephalon refers to the embryonic structure, from which the mature cerebrum develops...
, and the cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
. The norepinephrine from the LC has an excitatory effect on most of the brain, mediating arousal and priming the brain’s neurons to be activated by stimuli.
As an important homeostatic
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...
control center of the body, the locus coeruleus receives afferents from the hypothalamus. The cingulate gyrus and the amygdala also innervate the LC, allowing emotional pain and stressors to trigger noradrenergic responses. The cerebellum and afferents from the raphe nuclei
Raphe nuclei
The raphe nuclei are a moderate-size cluster of nuclei found in the brain stem. Their main function is to release serotonin to the rest of the brain...
also project to the LC, particularly the raphe pontis and raphe dorsalis.
The locus coeruleus receives inputs from a number of other brain regions, primarily:
- MedialMedial- Medial magmas :In abstract algebra, a medial magma is a set with a binary operation which satisfies the identity \cdot = \cdot , or more simply, xy\cdot uv = xu\cdot yv...
prefrontal cortexPrefrontal cortexThe prefrontal cortex is the anterior part of the frontal lobes of the brain, lying in front of the motor and premotor areas.This brain region has been implicated in planning complex cognitive behaviors, personality expression, decision making and moderating correct social behavior...
, whose connection is constant, excitatory, and increases in strength with raised activity levels in the subject - Nucleus paragigantocellularis, which integrates autonomicAutonomic nervous systemThe autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
and environmentNatural environmentThe natural environment encompasses all living and non-living things occurring naturally on Earth or some region thereof. It is an environment that encompasses the interaction of all living species....
al stimuli - Nucleus prepositus hypoglossiNucleus prepositus hypoglossiLocated in the medulla, the nucleus prepositus hypoglossi or NPH is part of the horizontal gaze holding system. It functions as a neural integrator....
, which is involved in gaze - Lateral hypothalamus, which releases orexinOrexinOrexins, also called hypocretins, are the common names given to a pair of excitatory neuropeptide hormones that were simultaneously discovered by two groups of researchers in rat brains....
, which, as well as its other functions, is excitatory in the locus coeruleus.
Function
The locus coeruleus may figure in clinical depressionClinical depression
Major depressive disorder is a mental disorder characterized by an all-encompassing low mood accompanied by low self-esteem, and by loss of interest or pleasure in normally enjoyable activities...
, panic disorder
Panic disorder
Panic disorder is an anxiety disorder characterized by recurring severe panic attacks. It may also include significant behavioral change lasting at least a month and of ongoing worry about the implications or concern about having other attacks. The latter are called anticipatory attacks...
, and anxiety
Anxiety
Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...
. Some medications including norepinephrine reuptake inhibitor
Norepinephrine reuptake inhibitor
A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
s (reboxetine
Reboxetine
Reboxetine is a drug marketed as an antidepressant for use in the treatment of clinical depression, panic disorder and ADD/ADHD, developed by Pharmacia . Its mesylate salt is sold under tradenames including Edronax, Norebox, Prolift, Solvex, Davedax or Vestra...
, atomoxetine), serotonin-norepinephrine reuptake inhibitor
Serotonin-norepinephrine reuptake inhibitor
Serotonin–norepinephrine reuptake inhibitors are a class of antidepressant drugs used in the treatment of major depression and other mood disorders...
s (venlafaxine
Venlafaxine
Venlafaxine is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. First introduced by Wyeth in 1993, now marketed by Pfizer, it is licensed for the treatment of major depressive disorder , as a treatment for generalized anxiety disorder, and comorbid indications in...
), and norepinephrine-dopamine reuptake inhibitor
Norepinephrine-dopamine reuptake inhibitor
A norepinephrine-dopamine reuptake inhibitor is a drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and dopamine by blocking the action of the norepinephrine transporter and the dopamine transporter , respectively...
s (bupropion
Bupropion
Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
) are believed to show efficacy by acting upon neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s in this area. This area of the brain is also intimately involved in REM sleep.
Psychiatric research has documented that enhanced noradrenergic postsynaptic responsiveness in the neuronal pathway (brain circuit) that originates in the locus coeruleus and end in the basolateral nucleus of the amygdala is a major factor in the pathophysiology of most stress-induced fear-circuitry disorders and especially in posttraumatic stress disorder (PTSD). The LC neurons are probably the origin of the first or second “leg” of what has been recently termed the "PTSD candidate circuit." Combat-related PTSD (in a 2005 study of deceased American army veterans from World War II) was shown to be associated with a postmortem diminished number of neurons in the locus coeruleus (LC) on the right side of the brain. The role of the LC in PTSD may explain the dramatic effectiveness of two generic medications, propranolol and prazosin
Prazosin
Prazosin, trade names Minipress, Vasoflex, Pressin and Hypovase, is a sympatholytic drug used to treat high blood pressure and Anxiety, PTSD and Panic Disorder. It belongs to the class of alpha-adrenergic blockers. Specifically, prazosin is selective for the alpha-1 receptors on vascular smooth...
for the secondary prevention and treatment of PTSD, respectively.
In stress
The locus coeruleus is responsible for mediating many of the sympathetic effects during stress. The locus coeruleus is activated by stress, and will respond by increasing norepinephrine secretion, which in turn will alter cognitive function (through the prefrontal cortex), increase motivation (through nucleus accumbensNucleus accumbens
The nucleus accumbens , also known as the accumbens nucleus or as the nucleus accumbens septi , is a collection of neurons and forms the main part of the ventral striatum...
), activate the hypothalamic-pituitary-adrenal axis
Hypothalamic-pituitary-adrenal axis
The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,...
, and increase the sympathetic discharge/inhibit parasympathetic tone (through the brainstem). Specific to the activation of the hypothalamo-pituitary adrenal axis, norepinephrine will stimulate the secretion of corticotropin-releasing factor from the hypothalamus, which induces adrenocorticotropic hormone
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
release from the anterior pituitary
Anterior pituitary
A major organ of the endocrine system, the anterior pituitary, also called the adenohypophysis, is the glandular, anterior lobe of the pituitary gland...
and subsequent cortisol synthesis in the adrenal glands. Norepinephrine released from locus coeruleus will feedback to inhibit its production, and corticotropin-releasing hormone will feedback to inhibit its production, while positively feeding to the locus coeruleus to increase norepinephrine production.
The LC's role in cognitive function in relation to stress is complex and multi-modal. Norepinephrine released from the LC can act on α2 receptors to increase working memory, or an excess of NE may decrease working memory by binding to the lower affinity α1 receptors.
In opiate withdrawal
OpioidOpioid
An opioid is a psychoactive chemical that works by binding to opioid receptors, which are found principally in the central and peripheral nervous system and the gastrointestinal tract...
s inhibit the firing of neurons in the locus coeruleus. When opioid consumption is stopped, the increased activity of the locus coeruleus contributes to the symptoms of opiate withdrawal. The alpha2 adrenoceptor agonist clonidine
Clonidine
Clonidine is a sympatholytic medication used to treat medical conditions, such as high blood pressure, some pain conditions, ADHD and anxiety/panic disorder...
is used to counteract this withdrawal effect by decreasing adrenergic neurotransmission from the locus coeruleus.
Rett syndrome
The genetic defect of the transcriptional regulator MECP2MECP2
MECP2 is a gene that provides instructions for making its protein product, MECP2, also referred to as MeCP2. MECP2 appears to be essential for the normal function of nerve cells. The protein seems to be particularly important for mature nerve cells, where it is present in high levels...
is responsible for Rett syndrome
Rett syndrome
Rett syndrome is a neurodevelopmental disorder of the grey matter of the brain that almost exclusively affects females. The clinical features include small hands and feet and a deceleration of the rate of head growth . Repetitive hand movements, such as wringing and/or repeatedly putting hands into...
. A MECP2 deficiency has been associated to catecholaminergic dysfunctions related to autonomic and sympathoadrenergic system in mouse models of Rett Syndrome (RTT). The Locus Coeruleus is the major source of noradrenergic innervation in the brain and sends widespread connections to rostral (cerebral cortex, hippocampus, hypothalamus) and caudal (cerebellum, brainstem nuclei) brain areas and. Indeed, an alteration of this structure could contribute to several symptoms observed in MECP2-deficient mice. Changes in the electrophysiological properties of cells in the locus ceruleus
Locus ceruleus
The locus coeruleus , is a nucleus in the brainstem involved with physiological responses to stress and panic. It was discovered in the 18th century by Félix Vicq-d'Azyr....
were shown. These Locus Coeruleus cell changes include hyperexcitability and decreased functioning of its noradrenergic innervation. Interestingly, a reduction of the tyrosine hydroxylase (TH) mRNA level, the rate-limiting enzyme in catecholamine synthesis, was detected in the whole pons of MECP2-null male as well as in adult heterozygous female mice. Using immunoquantification techniques, a decrease of TH protein staining level, number of locus coeruleus TH-expressing neurons and density of dendritic arborization surrounding the structure was shown in symptomatic MECP2-deficient mice. However, locus coeruleus cells are not dying but are more likely losing their fully mature phenotype since no apoptotic neurons in the pons were detected. Researchers have concluded that "Because these neurons are a pivotal source of norepinephrine throughout the brainstem and forebrain and are involved in the regulation of diverse functions disrupted in Rett Syndrome, such as respiration and cognition, we hypothesize that the locus ceruleus is a critical site at which loss of MECP2 results in CNS dysfunction. Restoration of normal locus ceruleus function may therefore be of potential therapeutic value in the treatment of Rett Syndrome. This could explain why a norepinephrine reuptake inhibitor (desipramine, DMI) which enhances the extracellular NE levels at all noradrenergic synapses ameliorated some Rett syndrome symptoms in a mouse model of Rett syndrome.
Alzheimer's disease
There is up to 70% loss of locus ceruleus neurons in Alzheimer's diseaseAlzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
. Mouse models of Alzheimer's disease show accelerated progression after chemical destruction of the locus ceruleus The norepinephrine from locus ceruleus cells in addition to its neurotransmitter role locally defuses from "varicosities". As such it provides an endogenous antiinflammatory agent in the microenvironment around the neurons, glial cell
Glial cell
Glial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...
s, and blood vessels in the neocortex and hippocampus. It has been shown that norepinephrine stimulates mouse microglia to suppress Aβ-induced production of cytokine
Cytokine
Cytokines are small cell-signaling protein molecules that are secreted by the glial cells of the nervous system and by numerous cells of the immune system and are a category of signaling molecules used extensively in intercellular communication...
s and their phagocytosis of Aβ. This suggests that degeneration of the locus ceruleus might be responsible for increased Aβ deposition in AD brains.
External links
- "A Lecture, Higher Brain Function: Activation of the Brain and Levels of Consciousness" at East Tennessee State UniversityEast Tennessee State UniversityEast Tennessee State University is an accredited American university located in Johnson City, Tennessee. It is part of the Tennessee Board of Regents system of colleges and universities, the nation's sixth largest system of public education, and is the fourth largest university in the state...
- Diagram at University of Texas at AustinUniversity of Texas at AustinThe University of Texas at Austin is a state research university located in Austin, Texas, USA, and is the flagship institution of the The University of Texas System. Founded in 1883, its campus is located approximately from the Texas State Capitol in Austin...
- Diagram at University of VirginiaUniversity of VirginiaThe University of Virginia is a public research university located in Charlottesville, Virginia, United States, founded by Thomas Jefferson...
- http://www2.umdnj.edu/~neuro/studyaid/Practical2000/Q45.htm
