Neuroscience
-
Heart rate variability (HRV),a measure of the fluctuations in the intervals between consecutive heartbeats, is an indicator of changes in the autonomic nervous system. A chronic reduction in HRV has been repeatedly linked to clinical depression. However, the chronological and mechanistic aspects of this relationship, between the neural, physiological, and psychopathological levels, remain unclear. ⋯ Lastly, we support this model by showing evidence that modification of HRV with biofeedback leads to an improvement in some symptoms of depression. The possibility that changes in HRV precede the onset of depression is critical to put to the test, not only because it could provide insights into the mechanisms of the illness but also because it may offer a predictive anddiagnosticphysiological marker for depression. Importantly, it could also help to develop new effective clinical interventions for treating depression.
-
Thioredoxin-reductase 2 (Txnrd2) belongs to the thioredoxin-reductase family of selenoproteins and is a key antioxidant enzyme in mammalian cells to regulate redox homeostasis. Here, we reported that Txnrd2 exerted a major influence in brain damage caused by Intracerebral hemorrhage (ICH) by suppressing endoplasmic reticulum (ER) stress oxidative stress and via Trx2/Prx3 pathway. Furthermore, we demonstrated that pharmacological selenium (Se) rescued the brain damage after ICH by enhancing Txnrd2 expression. ⋯ Mechanistically, we observed that loss of Txnrd2 leads to increased lipid peroxidation levels and ER stress protein expression in neurons and astrocytes. Additionally, it was revealed that Se effectively restored the expression of Txnrd2 in brain and inhibited both the activity of ER stress protein activity and the generation of reactive oxygen species (ROS) by promoting Trx2/Prx3 kilter when administrating sodium selenite in lateral ventricle. This study shed light on the effect of Txnrd2 in regulating oxidative stress and ER stress via Trx2/Prx3 pathway upon ICH and its promising potential as an ICH therapeutic target.
-
In this study, the electrophysiological and biochemical consequences of repeated exposure to morphine in male rats on glutamatergic synaptic transmission, synaptic plasticity, the expression of GABA receptors and glutamate receptors at the temporoammonic-CA1 synapse along the longitudinal axis of the hippocampus (dorsal, intermediate, ventral, DH, IH, VH, respectively) were investigated. Slice electrophysiological methods, qRT-PCR, and western blotting techniques were used to characterize synaptic plasticity properties. We showed that repeated morphine exposure (RME) reduced excitatory synaptic transmission and ability for long-term potentiation (LTP) in the VH as well as eliminated the dorsoventral difference in paired-pulse responses. ⋯ In sum, the impact of morphine may differ depending on the region of the hippocampus studied. A distinct change in the short- and long-term synaptic plasticity along the hippocampus long axis due to repeated morphine exposure, partially mediated by a change in the expression profile of glutamatergic receptor subunits. These findings can be useful in further understanding the cellular mechanism underlying deficits in information storage and, more generally, cognitive processes resulting from chronic opioid abuse.
-
The functional dichotomy of anatomical regions of the medial prefrontal cortex (mPFC) has been tested with greater certainty in punishment-driven tasks, and less so in reward-oriented paradigms. In the infralimbic cortex (IL), known for behavioral suppression (STOP), tasks linked with reward or punishment are encoded through firing rate decrease or increase, respectively. Although the ventral tegmental area (VTA) is the brain region governing reward/aversion learning, the link between its excitatory neuron population and IL encoding of reward-linked behavioral expression is unclear. ⋯ Pairing VTA glutamate inhibition with reward acquisition events reduced the weight of reward-target association expressed as a lower affinity for previously rewarded targets. For these intervals, fewer IL neurons per mouse trial showed FR decrease and were accompanied by an increase in the percentage of units with no change in FR or elevated FR. Together, we conclude that VTA glutamate neurons are likely involved in establishing IL inhibition states that encode reward acquisition, and subsequent reward-target association when a reward is omitted.
-
Neonatal encephalopathy (NE) impairs white matter development and results in long-term neurodevelopmental deficits. Leveraging prior findings of altered neuronal proteins carried by brain-derived extracellular vesicles (EVs) that are marked by a neural-specific cell surface glycoprotein Contactin-2 (CNTN2) in NE infants, the present study aimed to determine the correlation between brain and circulating CNTN2+-EVs and whether NE alters circulating CNTN2+-EV levels in mice. Brain tissue and plasma were collected from postnatal day (P)7, 10, 11, 15 mice to determine the baseline CNTN2 correlation between these two compartments (n = 4-7/time point/sex). ⋯ The findings establish a link for central CNTN2 and its release into circulation during early postnatal life. The immediate elevation and release of CNTN2 following NE highlight a potential molecular response shortly after a brain injurious event. Our findings further support the utility of circulating brain-derived EVs as a possible bioindicator of NE.