Nervous system

About: Nervous system is a research topic. Over the lifetime, 16729 publications have been published within this topic receiving 847181 citations.

Local synthesis and dual actions of progesterone in the nervous system: neuroprotection and myelination

Abstract: Progesterone (PROG) is synthesized in the brain, spinal cord and peripheral nerves. Its direct precursor pregnenolone is either derived from the circulation or from local de novo synthesis as cytochrome P450scc, which converts cholesterol to pregnenolone, is expressed in the nervous system. Pregnenolone is converted to PROG by 3beta-hydroxysteroid dehydrogenase (3beta-HSD). In situ hybridization studies have shown that this enzyme is expressed throughout the rat brain, spinal cord and dorsal root ganglia (DRG) mainly by neurons. Macroglial cells, including astrocytes, oligodendroglial cells and Schwann cells, also have the capacity to synthesize PROG, but expression and activity of 3beta-HSD in these cells are regulated by cellular interactions. Thus, Schwann cells convert pregnenolone to PROG in response to a neuronal signal. There is now strong evidence that P450scc and 3beta-HSD are expressed in the human nervous system, where PROG synthesis also takes place. Although there are only a few studies addressing the biological significance of PROG synthesis in the brain, the autocrine/paracrine actions of locally synthesized PROG are likely to play an important role in the viability of neurons and in the formation of myelin sheaths. The neuroprotective effects of PROG have recently been documented in a murine model of spinal cord motoneuron degeneration, the Wobbler mouse. The treatment of symptomatic Wobbler mice with PROG for 15 days attenuated the neuropathological changes in spinal motoneurons and had beneficial effects on muscle strength and the survival rate of the animals. PROG may exert its neuroprotective effects by regulating expression of specific genes in neurons and glial cells, which may become hormone-sensitive after injury. The promyelinating effects of PROG were first documented in the mouse sciatic nerve and in co-cultures of sensory neurons and Schwann cells. PROG also promotes myelination in the brain, as shown in vitro in explant cultures of cerebellar slices and in vivo in the cerebellar peduncle of aged rats after toxin-induced demyelination. Local synthesis of PROG in the brain and the neuroprotective and promyelinating effects of this neurosteroid offer interesting therapeutic possibilities for the prevention and treatment of neurodegenerative diseases, for accelerating regenerative processes and for preserving cognitive functions during aging.

Requirement of myeloid cells for axon regeneration.

Abstract: The role of CD11b+ myeloid cells in axonal regeneration was assessed using axonal injury models and CD11b-TK(mt-30) mice expressing a mutated HSV-1 thymidine kinase (TK) gene regulated by the myeloid-specific CD11b promoter. Continuous delivery of ganciclovir at a sciatic nerve lesion site greatly decreased the number of granulocytes/inflammatory monocytes and macrophages in the distal stump of CD11b-TK(mt-30) mice. Axonal regeneration and locomotor function recovery were severely compromised in ganciclovir-treated CD11b-TK(mt-30) mice. This was caused by an unsuitable growth environment rather than an altered regeneration capacity of neurons. In absence of CD11b+ cells, the clearance of inhibitory myelin debris was prevented, neurotrophin synthesis was abolished, and blood vessel formation/maintenance was severely compromised in the sciatic nerve distal stump. Spinal cord-injured axons also failed to regenerate through peripheral nerve grafts in the absence of CD11b+ cells. Therefore, myeloid cells support axonal regeneration and functional recovery by creating a growth-permissive milieu for injured axons.

Cell counts and maps in the larval central nervous system of the ascidian Ciona intestinalis (L.).

Abstract: Although the ascidian tadpole larva harbors a prospectively valuable prototype of the chordate nervous system, with extensively characterized neural plate cell lineages, the simple cellular composition of the resultant central nervous system (CNS) is not documented in detail. The average total number of cells in the larval CNS of Ciona intestinalis is 335 (range ±4, n = 3), 65 or 66 of which reside in the nerve cord of the tail. The estimates were made by tracing and counting the number of nuclei in serial semithin (1 mm) sections cut longitudinally through three larvae, fixed no later than 2 hours after hatching. Within a single fourth larva, L4, 266 cells constituted the CNS in the trunk region of the larva, 45 of which occurred within the visceral ganglion, 215 in the sensory vesicle, and 6 in the neck between the two. Each cell was assigned to one of thirteen categories. Most (182, roughly 68%) are classified as ependymal, a specialized non-neural cell peculiar to embryonic and larval chordates, from their position lining the cavities of the neural tube's elaborations or from clear similarities in the cytological appearance to those that do. Five cells are accessory cells of the sensory structures: three lens cells and a pigment-cup cell in the ocellus, and a single pigment cell in the otolith. Of the remaining 79 cells, 36 are sensory, 17 receptors in the ocellus and 19 presumed hydrostatic pressure receptors; these lie on the right and left, sides of the sensory vesicle, respectively. Eighteen of the visceral ganglion cells have been tentatively classified as neurons, as have the remaining 25 cells which form two clusters in the posterior region of the sensory vesicle.