Long‐term microglial and astroglial activation in the hippocampus of trimethyltin‐intoxicated rat: stimulation of NGF and TrkA immunoreactivities in astroglia but not in microglia

Abstract

In the present study we investigated the microglial and astroglial response after trimethyltin (TMT) exposure over a prolonged period of time. Male Wistar rats were given a single dose of TMT (8 mg/kg, i.p.) and survived 4, 7, 21, 60 and 180 days after the administration of the toxin. Histochemistry (Griffonia simplicifolia lectin staining) and immunocytochemistry for GFAP were applied to identify micro- and astroglial cells, respectively. To assess the trophic response of glial cells (NGF and TrkA expression), single or double staining experiments were performed. In addition, the biochemical evaluation of GFAP and NGF were carried out at chosen timepoints using immunoblotting technique and ELISA, respectively. The main findings of our study were as follows. (1) A protracted activation of microglia (at least up to 2 months posttreatment). (2) A long-lasting expression of GFAP immunoreactivity (at least up to 6 months posttreatment) and a steady increase in GFAP content (at least up to 2 months posttreatment). (3) The appearance of enormously enlarged, round-shape astrocytes exclusively localized to CA1 and observed 2 months posttreatment. (4) The stimulation of NGF and TrkA expression in reactive astrocytes. (5) The strongest activation of micro- and astroglia coincided with the most prominent neurodegeneration in the hippocampus, i.e., in CA4/CA3c and CA1. It is tempting to assume that the activation of glial cells in the hippocampal areas particularly vulnerable to TMT may affect neuronal fate after neurotoxic insult.

The effect of amphetamine analogs on cleaved microtubule-associated protein-tau formation in the rat brain

“…In this regard, it is noteworthy that numerous CNS insults (e.g. kainic acid, trimethyltin, traumatic brain injury) that have been shown to increase C-tau formation (Irazuzta et al, 2001, Gabbita et al, 2005 also increase GFAP, a marker of reactive gliosis (Brock and O'Callaghan, 1987, McCann et al, 1996, Koczyk and Oderfeld-Nowak, 2000, Little et al, 2002, Wang et al, 2004a, Guo et al, 2006. Furthermore, the results of the present experiment, in which the number of C-tau immunoreactive cells has been shown to be increased in the striatum following METH or AMPH treatment, but not MDMA or PMA treatment, are in agreement with previous studies that have examined GFAP immunoreactivity or protein expression.…”

Oxidative Stress and β-Amyloid Protein in Alzheimer’s Disease

“…Microglia-derived factors secreted in response to injury can trigger reactive astrocytosis (Conway et al 1998;Koczyk and Oderfeld-Nowak 2000). Microglia could be the real target of some stimuli, and subsequently, the stimulated microglia may activate astrocytes (Rathke-Hartlieb et al 1999).…”

“…Microglia could be the real target of some stimuli, and subsequently, the stimulated microglia may activate astrocytes (Rathke-Hartlieb et al 1999). The complexity of the interaction between astrocytes and microglia makes it very difficult to separate their activities (Koczyk and Oderfeld-Nowak 2000). Activated microglia and astrocytes are closely associated with formation of amyloid plaques in AD (Rathke-Hartlieb et al 1999;Rohl et al 2010;Schubert and Rudolphi 1998).…”

TrkA immunoreactive astrocytes in dendritic fields of the hippocampal formation across estrous

“…A number of studies have reported TrkA receptor and mRNA expression by astrocytes after trauma, neurodegenerative, and Alzheimer disease in the hippocampus and other brain regions (Aguado et al, 1998; Althaus and Richter-Landsberg, 2000; Koczyk and Oderfeld-Nowak, 2000). Activated astrocytes appear within hours in the nervous system in response to diverse physical and chemical conditions (Althaus and Richter-Landsberg, 2000), increase TrkA expression (Wang et al, 1998), and can respond to neurotrophins in a receptor-mediated pathway (Grove et al, 1996).…”