Microglia in the hypendyma of the rat subcommissural organ following brain lesion with serotonin neurotoxin

Abstract

The population of microglial cells in the subependymal layer of the subcommissural organ is sparse in normal adult rats. The number of microglial cells was substantially increased in this area following intraventricular injection of the serotonin neurotoxin 5,6-dihydroxytryptamine (5,6-DHT). In sections of plastic embedded material, 1 micron thick, the majority of phagocytic cells scattered in the subependymal layer had an appearance similar to that described in classical studies of microglial cells. At the electron microscopic level microglial cells exhibited the characteristic elongate nucleus with peripheral chromatin condensation. The perikaryon was scanty, containing strands of rough endoplasmic reticulum. The abundant organelles in the processes included Golgi complexes, mitochondria, rough and smooth endoplasmic reticulum as well as dense and multivesicular bodies. In addition, the processes contained phagocytosed axon terminals originating from the dense serotoninergic input to the subcommissural organ, which had degenerated on accumulating the serotonin neurotoxin. A fraction of the phagocytosed material was contained in subependymal subcommissural organ cells, astrocytes and oligodendrocytes. At the light microscopic level the phagocytosed terminals were visualized histochemically with Schmorl's reaction, which resulted in Prussian Blue precipitates. This allowed screening of microglial cells in complete series of sections through the well-defined subependymal layer of the subcommissural organ.

Loss of Serotonin Transporter Protein after MDMA and Other Ring-Substituted Amphetamines

“…In particular, the fact that MDMA and structurally related drugs (PCA, FEN) do not typically produce signs of glial activation in the context of selective 5-HT deficits (Rowland et al, 1993;O'Callaghan and Miller, 1994;Pubill et al, 2003;Wang et al, 2004Wang et al, , 2005Rothman et al, 2004;Thomas et al, 2004; but see Wilson et al, 1993;Aguirre et al, 1999;Orio et al, 2004) has led some of these investigators to reconsider the notion that substituted amphetamines produce neurotoxic effects. When considering these data, however, it is important to bear in mind that the effects of established 5-HT neurotoxins (5,7-DHT and 5,6-DHT) on glial responses have also been largely negative, particularly in brain regions removed from the site of intracerebral toxin injection (Stagaard et al, 1987;Hardin et al, 1994;Rowland et al, 1993;Bendotti et al, 1994;Dugar et al, 1998; but see Frankfurt et al, 1991;Dugar et al, 1998). Additional research is therefore needed to more fully characterize the determinants, timing, nature, and role of glial responses in the context of selective, chemical lesions limited to fine, relatively sparse brain 5-HT axon terminals.…”

Microglial response to degeneration of serotonergic axon terminals

“…After CNS injury, microglia exhibit alterations in a number of characteristic features: "activated microglia undergo morphologic changes (del Rio-Hortega, 1932), exhibit increased or novel expression of macrophage/ monocyte antigens (Flaris et al, 1993;Graeber et al, 1990b;Sedgwick et al, 1991), and in some circumstances they proliferate (Graeber et al, 1988b;Sjostrand, 1965Sjostrand, , 1966Streit and Kreutzberg, 1988) or become phagocytic (del Rio-Hortega, 1932;Rinaman et al, 1991;Stagaard et al, 1987;Streit and Kreutzberg, 1988). The response of microglia varies, depending on the nature of the injury, e.g., neuronal death, retrograde reaction to axotomy, or axonal degeneration (Finsen et al, 1993;Flaris et al, 1993;Gehrmann et al, 1991;Streit et al, 1989).…”

Inflammatory Response Associated with Axonal Injury to Spinal Motoneurons in Newborn Rats

“…Migration of the blood-derived macrophages to the target and local proliferation of microglia would be responsible for most, if not all, of the phagocytic reaction following neuronal degeneration related to indirect neuronal trauma [Barron et al, 1990;Fulcrand and Privat, 1977;Graeber et al, 1988;Stoll et al, 1989;Torvik and Soreide, 1975], or intraneural injection of toxic ricin [Ling et al, 1992;Ling and Leong, 1987;. With respect to excitotoxic substances or neurotoxins which are widely used to induce neurodegeneration, a dual source of phagocytes has been generally accepted when they are administered intracerebrally [Akiyama and McGeer, 1989;Coffey et al, 1988Coffey et al, , 1990Marty et al, 1991;Murabe et al, 1981], whereas a pure microglial reaction has been claimed after intraventricular administration, despite the remote discrete disruption of the BBB [Stagaard et al, 1987]. Precisely what factors trigger microglial activation and what contributes to the difference in recruitment of circulating macrophages still remains a mystery, but it is reasonable to assume that at least some of these factors originate from injured neurons.…”