Evaluation of NCS-1, DARPP-32, and neurotrophins in hippocampus and prefrontal cortex in rats submitted to sepsis

Abstract

Sepsis is defined as the host's reaction to infection and it is characterized by a systemic inflammatory response with important clinical implications. Central nervous system dysfunction secondary to sepsis is associated with local generation of pro- and anti-inflammatory cytokines, impaired cerebral microcirculation, disturbance of neurotransmitters, apoptosis, and cognitive impairment. It is known that during the process of learning and memory formation several pathways are involved such as dopaminergic and cholinergic systems. Thus, the objective of this study is to evaluate the neuronal calcium sensor (NCS-1) and dopamine-cAMP regulated phosphoprotein of 32,000 kDa (DARPP-32) expression as well as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) levels in prefrontal cortex and hippocampus of rats 12, 24, and 48 h after sepsis induction. To this aim, we used sham-operated Wistar rats or submitted to the cecal ligation and perforation procedure. After 12 and 24 h, there was an increase of NGF levels in hippocampus; and up to 48 h, a decrease of NCS-1 expression in prefrontal cortex, a decrease of BDNF levels in hippocampus and an increase of NGF levels in hippocampus. In conclusion, we believe that the low expression of NCS-1 in prefrontal cortex and low levels of BDNF in hippocampus may be associated with the pathophysiology of cognitive impairment during sepsis and a putative role of the dopaminergic system.

Sepsis sensitizes behavioural amphetamine responses while inducing inflammatory and neurotrophic vulnerability in the cecal ligation and puncture model

“…Neither CLP nor AMPH per se altered the NCS-1 levels compared with the Sham + Sal group. In contrast to our results, Comim et al (2014) demonstrate a decrease in the levels of NCS-1 in the frontal cortex 48 h after CLP. Considering that the present study evaluated the NCS-1 levels 30 days after CLP, this difference in the results may be due to the period after CLP in which this parameter was evaluated in both studies.…”

NCS-1 is a regulator of calcium signaling in health and disease

“…In Parkinson’s disease (PD), increased levels of NCS-1 mRNA were measured in substantia nigra neurons [70]. In a rat model, a significant decrease of NCS-1 levels in the prefrontal cortex was proposed to contribute to cognitive impairment during sepsis [71]. These studies convey preliminary insights in the complex roles for NCS-1 and they validate in vitro pathways.…”

Systemic Response to Infection Induces Long-Term Cognitive Decline: Neuroinflammation and Oxidative Stress as Therapeutical Targets

“…In systemic infection scenarios, such as observed in sepsis, it is not clear which mechanism triggers neuronal dysfunction. Previous report pointed to cytokines, including IL-1β, inducing synaptic dysfunction and, in consequence, diminishing levels of the neurotrophic factor BDNF (Mina et al, 2013;Comim et al, 2014;Moraes et al, 2015). Long-term consequences of infectious diseases in the brain could be directly associated with the intensity of inflammatory response or due to immune response to the presence of the pathogen in the cerebral tissue (Dorovini-Zis et al, 2011;Ferrari and Moreira, 2011;John et al, 2015;Konradt et al, 2016;Bentivoglio et al, 2018;Lebov et al, 2018).…”