Immunohistochemical evaluation of the protein expression of nerve growth factor and its TrkA receptor in rat limbic regions following electroshock seizures

Abstract

Repeated (but not acute) exposure to brief, noninjurious seizures evoked by minimal electroconvulsive shock (ECS) decreases neuronal death in limbic system and increases mRNA levels for nerve growth factor (NGF). Thus, the induction of NGF is a potential mechanism for the neuroprotection evoked by repeated ECS. The neuroprotective action of NGF is mediated by the TrkA receptor. This study determined whether repeated ECS exposure increased TrkA and NGF protein levels. To determine the functional significance of changes in these proteins, we compared the effects of ECS given daily either for 7 days (chronic ECS) or for 1 day (acute ECS). After chronic ECS, upregulation of both NGF and TrkA was found in perirhinal cortex, thalamus, and amygdala. In hippocampus, TrkA was upregulated in CA2, CA3 and CA4. NGF increase in hippocampus was found in CA1 and dentate gyrus. In frontal cortex and substantia innominata, an increase in NGF (but not in TrkA) was found. In most brain regions, TrkA and NGF remained unchanged after acute ECS. Our results demonstrate that repeated exposure to ECS causes an upregulation of TrkA and NGF proteins in several limbic areas in which neuroprotective effects are observed suggesting that NGF contributes to ECS-evoked neuroprotection.

The effect of mild stress stimulation on the nerve growth factor (NGF) and tyrosine kinase receptor A (TrkA) immunoreactivity in the paraventricular nucleus (PVN) of the hypothalamus and hippocampus in aged vs. adult rats

“…NGF-ir and TrkA-ir cells in the hypothalamus (including PVN) or hippocampal areas have been detected under physiological conditions in non-stressed adult rodents (Aloe et al, 1990;Badowska-Szalewska et al, 2006a, 2006bConti et al, 2009). Most researchers agree that both NGF and its receptor TrkA are continuously expressed throughout aging and at least the NGF level is unaltered in the hippocampus (Katoh-Semba et al, 1998;Kelly et al, 2000;Williams et al, 2005;Niewiadomska et al, 2006).…”

“…The same antibodies were used in our previous studies (Badowska-Szalewska et al, 2011a,b). The specificity of the NGF antibody applied here was tested by Western blotting by Conti et al (2009). The specificity of the TrkA antibody was examined by Lee et al (2008).…”

“…However, some researchers have noted a decrease in NGF levels within the hippocampus after exposure to certain acute and/or chronic stressors, for instance, after acute and chronic footshock or acute rotatory stress (Scaccianoce et al, 2000). On the other hand, Conti et al (2009) examining NGF and TrkA immunoreactivity, showed that repeated (but not acute) exposure to a minimal electroconvulsive shock caused an upregulation in the NGF-ir and TrkA-ir in some hippocampal regions of adult rats. These discrepant data can be explained by the nature of the stressors (e.g.…”

The rat perirhinal cortex: A review of anatomy, physiology, plasticity, and function

“…Although there are low levels of nerve growth factor (NGF) and TrkA present in the neocortex (Altar et al, 1991;Merlio et al, 1992), the other neurotrophins and their receptors are more widely expressed throughout the neocortex (Klein et al, 1990;Merlio et al, 1992;Altar et al, 1994). However, the parahippocampal region shows higher levels of neurotrophins compared to rest of the neocortex: NGF (Lin et al, 1996;Conti et al, 2009), brain-derived neurotrophic factor (BDNF, Sato et al, 1996;Vezzani et al, 1999;Engler-Chiurazzi et al, in press), NT-3 (Eagleson et al, 2001) and all three Trk receptors (Bengzon et al, 1993) have been shown to be strongly expressed in the perirhinal cortex. It must be noted that so far, no study has looked at NT-4/5 expression in the perirhinal cortex.…”

The TrkB-Positive Dopaminergic Neurons are Less Sensitive to MPTP Insult in the Substantia Nigra of Adult C57/BL Mice

“…While localization and function of GDNF receptors were potently documented, only few studies reported existence of Trk mRNAs in the nigrostriatal regions [31,52]. Although TrkA-containing cholinergic neurons were distributed in the cerebral cortex and basal forebrain regions [10,17,27], the previous studies denied positive localization of TrkA protein in nigral neurons [6,30,40]. On the other hand, apparently, distribution patterns and dynamic changes of TrkB and TrkC proteins remain obscure in the adult substantia nigra and particularly in Parkinsonian state.…”