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 in...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.展开更多
The purpose of the present study was to determine whether early alterations in glutamate signaling, via daily injections of the glutamate agonist, domoic acid (DOM;20 μg/kg), during a critical period of CNS developme...The purpose of the present study was to determine whether early alterations in glutamate signaling, via daily injections of the glutamate agonist, domoic acid (DOM;20 μg/kg), during a critical period of CNS development (PND 8 - 14), would result in temporal memory deficits and/or alterations in tyrosine hydroxylase (TH) immunoreactivity. As adults, subjects were assessed for temporal memory ability using a recency discrimination paradigm. Both number and duration of exploratory contacts directed at familiar objects, differing by one hour in recall delay, were measured. Analyses revealed that DOM-treated females demonstrated temporal memory dysfunction, as evidenced in a significantly lower proportion of total exploratory behaviour directed toward the remote object. Integrity of the dopamine system was assessed using immunohistochemistry to examine TH immunoreactivity in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Sections obtained from DOM-treated males had significantly less TH immunoreactivity in the right mPFC, while DOM-treated females had significantly greater TH immunoreactivity in the left core and right shell of the NAcc. These findings are discussed in context of early alterations to glutamate signaling in the development of human neuropsychiatric disorders.展开更多
文摘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.
文摘The purpose of the present study was to determine whether early alterations in glutamate signaling, via daily injections of the glutamate agonist, domoic acid (DOM;20 μg/kg), during a critical period of CNS development (PND 8 - 14), would result in temporal memory deficits and/or alterations in tyrosine hydroxylase (TH) immunoreactivity. As adults, subjects were assessed for temporal memory ability using a recency discrimination paradigm. Both number and duration of exploratory contacts directed at familiar objects, differing by one hour in recall delay, were measured. Analyses revealed that DOM-treated females demonstrated temporal memory dysfunction, as evidenced in a significantly lower proportion of total exploratory behaviour directed toward the remote object. Integrity of the dopamine system was assessed using immunohistochemistry to examine TH immunoreactivity in the prefrontal cortex (PFC) and nucleus accumbens (NAcc). Sections obtained from DOM-treated males had significantly less TH immunoreactivity in the right mPFC, while DOM-treated females had significantly greater TH immunoreactivity in the left core and right shell of the NAcc. These findings are discussed in context of early alterations to glutamate signaling in the development of human neuropsychiatric disorders.
