Abstract

The clinical presentation of schizophrenia involves a variety of symptoms, which in many cases include hallucinations and delusions. Experimentally revealed alterations in both pre-pulse inhibition (PPI) and latent inhibition (LI) are also apparent in individuals afflicted with this disorder. Many have speculated that altered synaptic connections are, in part, responsible for this subset of behavioral abnormalities. We have previously reported that neonatal chronic low-dose injections of domoic acid (DOM) produce adult rats with deficits in PPI and LI. The current study was conducted to determine whether this toxin-treatment would alter the degree of apoptosis occurring in the developing brain. Results revealed significant decreases in caspase-3 within the right prelimbic cortex (PrL) in both male and female DOM-treated rats suggesting that even modest alterations in glutamate (Glu) signaling during critical periods of central nervous system (CNS) maturation will modify ontogenetic processes in the prefrontal cortex (PFC) of the juvenile rat.

Highlights

  • Apoptosis is a form of programmed cellular death which, unlike necrosis, does not involve the release of harmful substances into the extra-cellular environment

  • We have previously reported that, as adults, rats that were chronically exposed to very low doses of domoic acid (DOM) during critical periods of central nervous system (CNS) maturation, demonstrate persistent behavioural abnormalities that are consistent with those observed within the clinical population and that are homologous with those reported in other animal models of this disorder

  • Results revealed statistically significant treatment effects with DOM-treated males demonstrating decreased optical density measurements in the right prelimbic cortex (PrL) [t(8) = −2.838, p = 0.022] (Figure 1 and Figure 2) and with DOMtreated females demonstrating decreased immunopositive cell counts in the right PrL [t(8) = −2.307, p = 0.050] (Figure 3). In addition to these statistically significant findings, a consistent tendency for decreased caspase-3 staining noted in DOM-treated rats compared to their saline counterparts

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Summary

Introduction

Apoptosis is a form of programmed cellular death which, unlike necrosis, does not involve the release of harmful substances into the extra-cellular environment. Three main pathways are involved in apoptotic signalling: the extrinsic pathway, the intrinsic pathway, and the perforin/granzyme. Each pathway leads to the activation of the so termed “execution pathway”; beginning with caspase-3 activation, and involving various mechanisms of cellular death (e.g. chromosomal degradation, cytoskeletal degradation, phagocytic uptake of apoptotic bodies) (reviewed in [1]). The quantification of activated capase-3 is a common marker for determining apoptotic cell death (reviewed in [2] [3]). How to cite this paper: Robbins, M.A., Ryan, C.L. and Doucette, T.A. (2016) Alterations in Caspase-3 in Juvenile Rats Treated Neonatally with Domoic Acid. Journal of Behavioral and Brain Science, 6, 357-363.

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