Neurosecretion: an overview | ScienceDirect Topics (2023)

Neurosekretion

Neurons are excitable cells that send their axons throughout the nervous system to release their neurotransmitters and neuromodulators primarily at specialized chemical synapses. Neurohumoral or neurosecretory cells form a unique subset of neurons whose axonal terminals are not associated with classical synapses. Two examples of neurosecretory cells in the hypothalamus are neuropituitary and hypophysiotropic cells. The prototypeThe neuropituitary cells are the magnicellular neurons of the hypothalamic paraventricular nucleus (PVH) and the supraoptic nucleus (SON).hypophysiotropic cellsIt includes all neurons that secrete their products into the portal vessels of the pituitary gland in the middle eminence.Figure 7.1).

Neurosecretory cells, at their simplest, are neurons that secrete substances directly into the bloodstream to act as hormones. the theory ofNeurosekretionemerged from Scharrer's groundbreaking work,³who used morphological techniques to identify stained secretory granules in SON and HPV neurons. They found that cutting the pituitary stalk resulted in accumulation of these granules in the hypothalamus, leading them to hypothesize that hypothalamic neurons were the source of substances secreted by the neural lobe (posterior pituitary gland). It is now well established that axon terminals in the neural lobe arise from magnicellular SON and HPV neurons containing oxytocin and the antidiuretic hormone arginine vasopressin (AVP).

The modern definition ofNeurosekretionit evolved to involve the release of any neuronal secretion product from a neuron. In fact, a fundamental tenet of neuroscience is that all neurons in the CNS, including neurons that secrete AVP and oxytocin in the neural lobe, receive multiple synaptic inputs primarily at their dendrites and cell bodies. In addition, neurons have the fundamental ability to recognize and integrate inputs from multiple neurons through specific receptors. They, in turn, fire action potentials that result in the release of neurotransmitters and neuromodulators at synapses formed with postsynaptic neurons. The vast majority of communication between neurons is carried out by classical, fast-acting neurotransmitters (e.g. glutamate, γ-aminobutyric acid [GABA], acetylcholine) and neuromodulators (e.g. dopamine, epinephrine, norepinephrine, neuropeptides) that act on chemical synapses work.^18,19Neurosecretion represents a fundamental concept to understand the mechanisms used by the nervous system to control behavior and maintain homeostasis.

In the age of optogenetics, multidimensional omics, and personalized medicine, the importance of these early observations is often not fully appreciated. However, the reports of these early studies are instructive, and it is no exaggeration to say that the confirmation of the neurosecretion hypothesis represented one of the greatest advances in the field of neuroscience and neuroendocrinology. In fact, this and other early experiments, including the pioneering work of Geoffrey Harris,⁶led to the fundamental concept that the hypothalamus secretes hormones directly into the bloodstream (pituitary neural cells). These observations provided the principles upon which the modern discipline of neuroendocrinology is built.

Neurosekretiongenerally understood as the release of peptides or amines from specialized neurons into the circulation. In mammals, the classical neurosecretory systems secrete oxytocin or vasopressin from the axon terminals of the posterior pituitary and also peptides and amines, which control the anterior pituitary, from the terminals of the middle eminence. Invertebrates have other systems not considered here, but with similar functions. Peptides and amines are packed into dense vesicles that are released by exocytosis. The mechanism of exocytosis is similar to that of other cells and requires an increase in intracellular calcium. It is also known that neurosecretory neurons exocytose dense-nucleated vesicles from their dendrites. Dendritic secretion appears to be a general property of peptidergic neurons with widespread organizational functions in the central nervous system.

Increased intracellular formation of key advanced glycation endproducts - methylglyoxal precursors

Post-translational modifications of proteins, so-called advanced glycation end-products (AGEs), are formed by glucose-derived dicarbonyls that react with amino groups of unprotonated lysine and arginine residues of proteins. Methylglyoxal, formed by the non-enzymatic cleavage of the glycolytic intermediate triosephosphate, is responsible for most of the hyperglycemia-induced increase in AGE adducts in diabetic tissues.⁵⁴Intracellular methylglyoxal is detoxified by the glyoxalase system.⁵⁵The enzyme glyoxalase I, together with glyoxalase II and a catalytic amount of glutathione, reduces this highly reactive α-oxoaldehyde to D-lactate (Figure 37.6). In cells, methylglyoxal reacts with unprotonated arginine residues to form the major methylglyoxal-derived epitope MG-H1 (methylglyoxalhydroimidazolone 1). Intracellular production of AGE precursors damages target cells through three general mechanisms (Figure 37.7). First, modification of intracellular proteins by AGE alters their function. Second, AGE modification of extracellular matrix components alters their interaction with other matrix components and with matrix integrin receptors. Third, intracellular methylglyoxal increases expression of both the pattern recognition receptor for AGE (RAGE) and its major endogenous ligands, the pro-inflammatory calgranulins S100.⁵⁶Binding of these ligands to RAGE causes a cooperative interaction with the innate immune system's Toll-like receptor 4 (TLR4) signaling molecule.⁵⁷RAGE expression, S100A8, S100A12 and high mobility groupbox 1(HMGB1) are increased by high glucose concentrations in cell cultures and in diabetic animals. This hyperglycemia-induced overexpression is mediated by ROS-induced increases in methylglyoxal, which enhance binding of the transcription factors nuclear factor κB (NFκB) and activator protein 1 (AP1) to RAGE promoters and RAGE ligands, respectively.⁵⁶

Diabetes increases the levels of the major adduct derivative of methylglyoxal in the retina, renal glomerulus and sciatic nerve of rats.^58,59In the retina, diabetic mice with knockout of four transient potential cation channels (Trpc1/4/5/6 mice) have increased glyoxalase-1 activity and protein, protecting them from the initial phenotype of diabetic retinopathy, pericytic defect and capillarity. acellular formation.⁶⁰In the kidneys of non-diabetic mice, glyoxalase I (GLO1) degradation increases to diabetic levels, both methylglyoxal modification of glomerular proteins and oxidative stress, resulting in changes in renal morphology indistinguishable from those caused by diabetes. , while in the kidneys of diabetic mice, overexpression of GLO1 completely prevents the diabetes-induced increase in glomerular protein modification by methylgloxal, increased oxidative stress and the development of diabetic renal pathology, despite unchanged levels by diabetic hyperglycemia.⁶¹

IX Environmental and somatic signals that regulate GnRH neurosecretion

NeurosekretionGnRH levels are also regulated by numerous physiological signals from non-gonadal sources. These include sensory stimuli, information retrieved from memory, and circulating hormonal and metabolic factors. Perhaps the most studied of these regulatory inputs are photoperiodic stimuli. In seasonally reproducing animals, day length is recorded via light pathways that ultimately regulate the pineal gland's pattern of melatonin secretion. Changes in the duration of melatonin secretion from the pineal gland, in turn, activate or suppress GnRH pulse generation and thus preserve or suppress activity in the reproductive axis. In hamsters, long days are photostimulatory to the reproductive axis and these responses are likely mediated by activation and inhibition of the GnRH pulse generator, respectively. In sheep, exposure to short days stimulates GnRH pulsatility while long days are photoinhibitory; This mechanism determines the birth of the young in the spring, when the chances of survival are greatest.

There are many other examples of reproductively relevant sensory cues that cause adaptive changes in GnRH pulse amplitude or rate. GnRH pulses are acutely stimulated in ewes after visual exposure to rams, coitus induces an ovulatory surge of GnRH in rabbits by activating sensory pathways from the cervix to the hypothalamus, and pheromone signaling from male mice is extremely important for the release of GnRH spikes in female mice . In all these circumstances, the reflex pathways transmit information about the presence of a sexual partner and the GnRH pulse generator is activated to prepare the gonads for fertilization.

Chronic and acute stress can also alter the pattern of pulsatility, often in an inhibitory manner, to favor metabolic energy expenditure in adaptive stress responses rather than reproduction. Metabolic and hormonal signals such as glucose, leptin, insulin, IGFs, thyroid hormones or glucocorticoids may also be important in mediating the adaptive physiological responses of the GnRH pulse generator. Food deprivation, for example, is a condition incompatible with reproductive success; hence it is not surprising that in many species it is accompanied by suppression of the GnRH pulse generator. This regulatory mechanism can also prevent the energy reserves from being used up during incubation attempts under harsh environmental conditions. In disease states, GnRH pulsatility may also be suppressed. Immune stress and inflammatory responses may be accompanied by suppression of the GnRH pulse generator, possibly through the action of cytokines known to occur under these conditions.

pituitary

Öpituitary(pituitary) is a small bean-shaped gland about 1 cm in diameter at the base of the brain below the third ventricle, located in a bony cavity at the base of the skull (theTurkish Sela). The gland is divided into anterior and posterior parts that have different embryological origins, functions, and control mechanisms.

The secretion of all major pituitary hormones is controlled by the hypothalamus, which is under the influence of nerve stimuli from the higher centers of the brain. Control is primarily through feedback of circulating levels of hormones produced by pituitary-dependent endocrine tissues.

Not always multiple types of channels

AlthoughNeurosekretionWhile more than one channel type is supported at most CNS synapses, transmission at some synapses can be strongly dominated by a single channel type. Examples include some historically important preparations for discovering the basic principles of neurotransmission, such as the mammalian neuromuscular synapse and the giant squid synapse, where P-type or P/Q-type channels predominate. At some hippocampal inhibitory synapses, GABA release is entirely mediated by P/Q-type or N-type Ca.²⁺Channels Neurotransmission at sympathetic neuroeffector junctions is controlled almost exclusively by N-type channels Differences in the dependence of different Ca_v2 Family members gain additional importance when targeting synaptic circuits for pharmacological and possibly therapeutic interventions. For example, in the dorsal horn of the spinal cord, the major component in the pain transmission/modulation circuitry, P/Q-type Ca inhibitory synaptic transmission is dominated.²⁺Channels; in contrast, N-type channels are more closely associated with glutamate release from peptidergic primary sensory neurons that relay nociceptive information to the dorsal horn.

Publisher's summary

to the theory ofNeurosekretionit is originally based on histological evidence. Combined histological and physiological evidence provided compelling evidence for neurosecretion in the central nervous system (CNS) of annelids, crustaceans, and insects. The chapter mainly deals with the neurosecretory systems of these groups. Cells containing abundant secretory inclusions are widespread in the brain and other parts of the CNS of most invertebrates. The functional importance of many of these cells is unclear, although in many cases a correlation between the frequency of secretory inclusions and developmental stages has been observed. There are distinct well-defined neurosecretory pathways in annelids and arthropods, each consisting of cell bodies, axonal fibers containing secretory material, and fiber ends that comprise a neurohemal organ. Physiological evidence has shown functional importance for these neurosecretory systems.

10.4.3 Neurosecretory Substances

although the termNeurosekretiongenerally refers to "classic" peptidergic (assuming specific sites) neurosecretory granules within the neurosecretory cell and its axons, and also refers to the substances actually released from these axons into the hemolymph at levels consistent with the physiological Vary state of the organism. In a broader sense, the term neurosecretion can be applied to other low molecular weight substances, such as e.g. B. the Bursicon peptide, which is released from the rectal wall of the intestineLeukofea(Holman & Cook, 1972) and catecholamines in the salivary nerves of some insects (Bracket, 1972;Markeand another1973;Hausand another1973;Robertsson, 1975). In cases of localized hormone release where the substance cannot be detected by conventional neurosecretory stains, the term “neuronal secretomotor substance” makes more sense (Madrel, 1974), However. Histological studies ofObenchain and Oliver (1975)and ultrastructural observations ofNathanson (1969), which proved the presence ofConventionally stained neurosecretory granules in the peripheral nervous system at points more distal than known neurohemic organs suggest that peptidergic neurohormones may be released near effector organs.variable dEvidence for the presence of other neurosecretomotor substances in ticks comes from the detection of catecholamines by the Falck-Hillarp technique in the foot, palpal, salivary, and opisthosomal organs.nerves ofB microplusand within the varicose veins of the nerve endings in the three types of acini of the salivary glands, as well as in the nerve endings connected to the epidermal structures (Binnington & Stone, 1977). Within the synganglia, catecholamine-containing paired cell bodies were largely restricted to the ventral regions of the cortex, where aggregations of neurons sent their axons dorsally to the neuropil of the corresponding ganglia. Axons from a paired group of large cells located posterodorsally in the fourth pedal ganglion (Figure 10.14) were traced through the neuropil to the opisthosomal nerves. The neuropil of the sinanglion (Figure 10.15), particularly in the area of ​​the foot ganglia, was rich in fluorescent varices, suggesting that catecholamines can be used for both central synaptic transmission and peripheral release.

2.3 Temporal Aspects of Neural Regulation of the Endocrine System

A common feature ofNeurosekretionis the impressive rhythm of hormone release (see Akil et al.1999, Frohmannet al.1999). Circulating hormone levels, controlled by hypothalamic-pituitary regulation, normally fluctuate with a daily or "circadian" rhythm of about 24 hours. Superimposed on the circadian rhythm is a faster "ultradian" pattern of discrete hormonal pulses that also has a regular rhythm. The ultradian secretion period of the hormone varies by species. In humans, the typical pattern of anterior pituitary hormone secretion is a series of spikes at 90-120 minute intervals, with the peak concentration of the spikes varying systematically with the time of day. The temporal pattern of circadian and pulsatile hormone secretion is thought to result from the activity pattern of neurosecretory cells in the hypothalamus. Therefore, an important role of the brain in regulating the endocrine system may lie in the timing of hormone fluctuations. The suprachiasmatic nucleus of the hypothalamus has a clock function in the brain, and there are likely other circadian and ultradian clocks in the brain.

The pineal gland has the unique function of integrating sensory and endocrine functions. In lower vertebrates, the pineal gland is actually a light-sensitive third eye (Dodt and Meiss1982). Photoreceptive capacity appears to have been lost in mammals, but the role of the pineal gland is still related to phototic input. Innervation of the mammalian pineal gland involves multisynaptic inputs from the retina, particularly via the suprachiasmatic nucleus of the hypothalamus, and the pineal hormone melatonin is secreted predominantly at night.

IV.B.1.c Diffuse release sites

Immunostaining with antibodies againstneurosecretionshowed that the perivisceral organs are not exclusive sites of release of neurosecretory cells from the ventral ganglia. The axons of some of these cells emerge from peripheral nerves and form networks in the sheath that surrounds the nerve. The bullous or variceal morphology of these networks suggests that they release their product into the hemolymph and can therefore form a large diffuse neurohemal area.Figure 9). In tobacco armyworm larvae and pupae, axons from brain cells that produce the hatching hormone (one of a cascade of hormones involved in moulting) travel to the final node in the abdomen and release its hormone into the hemolymph, from the nerve surface to the rectum