Nervous system disorders in a patient with Adie syndrome (a clinical case)

Holmes-Adie syndrome, or tonic pupil syndrome, is a condition characterized by a triad of main symptoms: unilateral tonic pupil dilation, accommodative paresis without or with a significant reduction in pupillary light reflex, and decreased tendon reflexes. The disease is based on dysfunction of the parasympathetic nervous system. The syndrome results from damage to the ciliary ganglion, which carries parasympathetic innervation to the m.sphincter pupillae, cornea, and eyeball. Often the condition is accompanied by dysfunction of the spinal ganglia and, as a consequence, autonomic dysfunction in the form of sweating disorders, usually on one side of the body, rarely — by heart rhythm disorders, lability of blood pressure. A frequent sign of Adie syndrome is the absence or reduction in patellar, rarely Achilles, reflexes. The etiology of the disease is not definitively determined, bacterial or viral factors are not excluded. The diagnosis of Adie syndrome is mainly based on a clinical comparison of the symptoms of the disease, as well as on a thorough and comprehensive examination by a neuroophthalmologist with mandatory testing of pupillary responses with low doses of pilocarpine (narrowing of the pupil is characteristic). Despite the positive prognosis for the patient’s life and his ability to work, the condition belongs to the group of difficult-to-treat ones, and the management consists in symptomatic vision correction.

Nicotinic acetylcholine receptor redux: Discovery of accessories opens therapeutic vistas

The neurotransmitter acetylcholine (ACh) acts in part through a family of nicotinic ACh receptors (nAChRs), which mediate diverse physiological processes including muscle contraction, neurotransmission, and sensory transduction. Pharmacologically, nAChRs are responsible for tobacco addiction and are targeted by medicines for hypertension and dementia. Nicotinic AChRs were the first ion channels to be isolated. Recent studies have identified molecules that control nAChR biogenesis, trafficking, and function. These nAChR accessories include protein and chemical chaperones as well as auxiliary subunits. Whereas some factors act on many nAChRs, others are receptor specific. Discovery of these regulatory mechanisms is transforming nAChR research in cells and tissues ranging from central neurons to spinal ganglia to cochlear hair cells. Nicotinic AChR–specific accessories also enable drug discovery on high-confidence targets for psychiatric, neurological, and auditory disorders.

Spinal ganglia control nociceptive input to the central nervous system

Accumulating observations suggest that peripheral somatosensory ganglia may regulate pain transmission, yet direct evidence is sparse. Here we show that the peripheral afferent nociceptive information undergoes dynamic filtering within dorsal root ganglia (DRG) and suggest that this filtering occurs at the axonal bifurcations (t-junctions). Using simultaneous in vivo electrophysiological recordings from the peripheral (spinal nerve) and central (dorsal root) aspects of rodent spinal nerves, ganglionic transplantation of GABAergic progenitor cells, and optogenetics we demonstrate tonic and dynamic filtering of action potentials traveling through the DRG. Filtering induced by focal application of GABA or optogenetic GABA release from the DRG-transplanted GABAergic progenitor cells was specific to nociceptive fibers. Light-sheet imaging and computer modeling demonstrated that, compared to other somatosensory fiber types, nociceptors have shorter stem axons, making somatic control over t-junctional filtering more efficient. Optogenetically-induced GABA release within DRG enhanced filtering and reduced both acute and chronic inflammatory and neuropathic pain in vivo. These findings support the potential gating of pain information within the somatosensory system, and suggests new therapeutic approaches for pain relief.

The nerve supply of the mammary gland

Proper development and functioning of the mammary gland depends not only on hormones, but also on the nervous system. The aim of this paper was to summarize the existing knowledge on the innervation of the mammary gland in various mammalian species, including domestic animals. In general, the pattern of innervation of this gland is similar in all studied species, i.e. large farm animals, rodents, dogs and beavers, as well as humans. Using the pan-neuronal marker of neural structures PGP-9.5, it was found that the mammary gland is well supplied with nerve fibres. Very rich innervation was discovered in the nipple, and less numerous nerve endings were found in the parenchyma. Nerve fibres supply the skin, especially the nipple, and many nerve terminals are associated with blood vessels and smooth muscles throughout the organ. Immunohistochemical investigations have made it possible to distinguish two major subpopulations of nerve fibres supplying the mammary gland. One of them consists of putative sensory fibres expressing CGRP, SP, GAL and/or PACAP, and the other is presumably composed of adrenergic axons containing TH, DBH, SOM and/or VIP. Studies on the sources of innervation of the mammary gland have confirmed assumptions about the nature of the nerve fibres and have revealed that they derive from the spinal ganglia (DRG) and sympathetic trunk ganglia (SChG). In the rat, mammary gland-projecting (MGP) neurons were also found in the nodose ganglion. So far, the rat and the pig have been tested most comprehensively for the sources of the mammary gland innervation. The MGP sensory neurons were observed ipsilaterally in several consecutive DRG, suggesting that the same neurons supply several successive glands. In the case of the SChG, it was found that MGP neurons are located, among others, in the L1-L4 ganglia, which constitute a specific „mammary gland nerve centre”. Previous studies on the sources of nerve supply to female reproductive organs have revealed that the SChG L1-L4 ganglia also contain nerve cells that project to the ovary, fallopian tube and uterus. Some clinical implications of the mammary gland innervation are also discussed.

A.S.Dogel Histological research. Issue I. Zap. Imper. Academy of Sciences, vol. VII oy; E. Heimann. Beitrage zur Kenntniss der feineren Structur der Spinalganglien. Virchow's Archiv., Bd. 152, IL 2., p. 298 .; On the same. Ueber die feinere Structur der Spinalgan- glienzellen. Fortschritte der Medic. 1898. Bd. 16, no. 9; Van Gehuchten and Ch. Nelis. Quelques points concernant la structure de cellules des ganglions spinaux. "La Cellule", recueil de cytologie et d'histologie generale. 1898 2nd issue; Vladislav Kuzicka. Untersuchungen über die feinere Structur der Nervenzellen und ihrer Fortsatze. Archiv. f. microsc. Anat. 1899 H. 4, Bd. 53

A.S.Dogel (1) comes back to the question of the structures of nerve cells in general and tries to approach it with the help of Ehrlich's methods. So on this connector he studies, among other things, the structure of the spinal ganglia of many mammals.

Morphology of spinal ganglia of different segmentary levels in the domestic dog

The spinal ganglia, which perform the function of the first link on the afferent impulses’ way from the receptors to the central nervous system, recognize internal and external irritations, and are the first to transform them into a nervous impulse. As the representatives of the peripheral nervous system, they are some of the main objects of the studies in contemporary neuromorphology. Based on the results of anatomic, neurohistological, histochemical, morphometric and statistical methods of the studies, we conducted a complex survey, revealing the morphology of spinal ganglia of different segmental levels in the domestic dog. In particular, we determined the differences in the microscopic structure and morphometric parameters of cervical, thoracic, lumbar and sacral spinal ganglia and the ganglia of the cervical and lumbar enlargements in mature domestic dogs. The study showed that the spinal ganglia of domestic dogs can have different skeletotopy, different shape and sizes due to their species peculiarity. Also, the surveyed animals, according to the results of our studies, had the cervical and thoracic spinal ganglia of oval, while the lumbar and sacral – spindle-like shapes. According to the results of morphometry, the area of the spinal ganglia in lengthwise section differed: the smallest area belonged to the thoracic, the largest to the sacral spinal ganglia. The density of neuronal arrangement per 0.1 mm2 of the area of the spinal ganglia correlated with their sizes: the highest parameter was identified for the thoracic spinal ganglia, the lowest – for the sacral. The conducted studies revealed that histo- and cyto-structure of the spinal ganglia is characteristic of notable differentiation of the nervous cells of small sizes. Therefore, we differentiated neurons of the spinal ganglia into large, medium and small. The highest quantity of large neurons was found in the sacral ganglia, and largest amount of medium-sized neurons – in the ganglia of the lumbar enlargement. In other ganglia, small neurons dominated. Correspondingly, different nuclear-cytoplasmic ratio in these neurons was determined, indicating different extent of morphofunctional condition of nervous cells. We determined content of localization and separation of nucleic acids in histostructure of the spinal cord at the tissue and cellular levels.