Changes in motor behavior and lumbar motoneuron morphology following repeated chlorpyrifos exposure in rats.

Chlorpyrifos is an organophosphate pesticide associated with numerous health effects including motor performance decrements. While many studies have focused on the health effects following acute chlorpyrifos poisonings, almost no studies have examined the effects on motoneurons following occupational-like exposures. The main objective of this study was to examine the broad effects of repeated occupational-like chlorpyrifos exposures on spinal motoneuron soma size relative to motor activity. To execute our objective, adult rats were exposed to chlorpyrifos via oral gavage once a day, five days a week for two weeks. Chlorpyrifos exposure effects were assessed either three days or two months following the last exposure. Three days following the last repeated chlorpyrifos exposure, there were transient effects in open-field motor activity and plasma cholinesterase activity levels. Two months following the chlorpyrifos exposures, there were delayed effects in sensorimotor gating, pro-inflammatory cytokines and spinal lumbar motoneuron soma morphology. Overall, these results offer support that subacute repeated occupational-like chlorpyrifos exposures have both short-term and longer-term effects in motor activity, inflammation, and central nervous system mechanisms.

Vagus nerve stimulation-induced cognitive enhancement: Hippocampal neuroplasticity in healthy male rats.

BACKGROUND: Vagus nerve stimulation (VNS) improves cognition in humans and rodents, but the effects of a single session of VNS on performance and plasticity are not well understood. OBJECTIVE: Behavioral performance and hippocampal (HC) electrophysiology/neurotrophin expression were measured in healthy adult rats after VNS paired training to investigate changes in cognition and synaptic plasticity. METHODS: Platinum/iridium electrodes were surgically implanted around the left cervical branch of the VN of anesthetized male Sprague-Dawley rats (N = 47). VNS (100 µs biphasic pulses, 30 Hz, 0.8 mA) paired Novel Object Recognition (NOR)/Passive Avoidance Task (PAT) were assessed 24 h after training and post-mortem tissue was collected 48 h after VNS (N = 28). Electrophysiology recordings were collected using a microelectrode array system to assess functional effects on HC slices 90 min after VNS (N = 19). Sham received the same treatment without VNS and experimenters were blinded. RESULTS: Stimulated rats exhibited improved performance in NOR (p < 0.05, n = 12) and PAT (p < 0.05, n = 14). VNS enhanced long-term potentiation (p < 0.05, n = 7-12), and spontaneous spike amplitude (p < 0.05, n = 7-12) and frequency (p < 0.05, n = 7-12) in the CA1. Immunohistochemical analysis found increased brain-derived neurotrophic factor expression in the CA1 (p < 0.05, n = 8-9) and CA2 (p < 0.01, n = 7-8). CONCLUSION: These findings suggest that our VNS parameters promote synaptic plasticity and target the CA1, which may mediate the positive cognitive effects of VNS. This study significantly contributes to a better understanding of VNS mediated HC synaptic plasticity, which may improve clinical utilization of VNS for cognitive enhancement.

Effects of transcranial direct current stimulation on brain cytokine levels in rats.

Transcranial direct current stimulation (tDCS) has shown therapeutic potential to mitigate symptoms of various neurological disorders. Studies from our group and others used rodent models to demonstrate that tDCS modulates synaptic plasticity. We previously showed that 30 min of 0.25 mA tDCS administered to rats induced significant enhancement in the synaptic plasticity of hippocampal neurons. It has also been shown that tDCS induces expression of proteins known to mediate synaptic plasticity. This increase in synaptic plasticity may underly the observed therapeutic benefits of tDCS. However, the anti-inflammatory benefits of tDCS have not been thoroughly elucidated. Here we report that three sessions of tDCS spaced 1-3 weeks apart can significantly reduce levels of several inflammatory cytokines in brains of healthy rats. Rats receiving tDCS experienced enhanced synaptic plasticity without detectable improvement in behavioral tests or significant changes in astrocyte activation. The tDCS-mediated reduction in inflammatory cytokine levels supports the potential use of tDCS as a countermeasure against inflammation and offers additional support for the hypothesis that cytokines contribute to the modulation of synaptic plasticity.

Altered hippocampal function and cytokine levels in a rat model of Gulf War illness.

AIMS: Gulf War illness (GWI) is a disorder affecting military personnel deployed in the Gulf War (GW) from 1990 to 1991. Here, we will use a rat model of GWI to evaluate hippocampal function and cytokine levels. MATERIALS AND METHODS: Rats were exposed to diethyltoluamide and permethrin via dermal absorption and pyridostigmine bromide via gavage with or without a 5-min restraint for 28 days. Immediate and delayed effects of GW chemical exposure were evaluated using electrophysiology to quantitate hippocampal function, behavioral tests to assess cognitive effects and biochemical assays to measure neurotransmitter and cytokine levels. KEY FINDINGS: Behavioral data revealed a statistically significant increase in motor activity at 3 months following completion of exposures, potentially indicating increased excitability, and/or restlessness. Electrophysiology data revealed statistically significant changes in paired pulse facilitation and input-output function of CA1 hippocampal neurons within 24 h and 3 months following completion of exposures. There was also a statistically significant reduction in the frequency of spontaneous firing activity of hippocampal neurons within 24 h following exposures. Naïve hippocampal slices directly incubated in GW chemicals also resulted in similar changes in electrophysiological parameters. Biochemical measurements revealed reduced hippocampal glutamate level at 3 months post-exposure. Furthermore, there was a statistically significant increase in plasma and hippocampal levels of IL-13, as well as decrease in plasma level of IL-1ß. SIGNIFICANCE: Our data support an effect on glutamate signaling within the hippocampus as indicated by changes in PPF and hippocampal level of glutamate, with some activation of T helper type 2 immune response.