Electrophysiological and inflammatory changes of CA1 area in male rats exposed to acute kidney injury: Neuroprotective effects of erythropoietin

The high mortality rate associated with acute kidney injury (AKI) is commonly due to progressive, inflammatory multiple organ dysfunction, which often involves neurological complications. The AKI-stimulated mechanisms leading to brain dysfunction are not well understood, which hinders development of new therapeutic avenues to minimize AKI-mediated neural effects. The hippocampal CA1 area is a particularly vulnerable region during AKI but the electrophysiological and inflammatory mechanisms involved in this vulnerability remain largely unknown. Here, we used immunohistochemistry to quantitatively investigate the number of astrocytes expressing glial �brillary acidic protein (GFAP) as an indicator of inflammation, and whole cell patch clamp to evaluate electrophysiological changes in CA1 at different time points following induction of bilateral renal ischemia (BRI) in male Wistar rats. Further we evaluated the effectiveness of erythropoietin (EPO, 1000 U/kg i.p.) in mitigating BRI-associated changes. Plasma concentrations of blood urea nitrogen (BUN) were signi�cantly enhanced at 24 h, 72 h and 1 week, and creatinine (Cr) was increased at 24 h after reperfusion, which were changes reduced by EPO. BRI led to an increase in CA1 GFAP-positive cells 24 h and 72 h, but not 1 week, after reperfusion, and EPO reversed this effect of BRI at 24 h. Additionally, BRI caused an increase in the peak amplitude and coefficient of variation of CA1 pyramidal neuronal action potentials, which were changes not seen in presence of EPO. When taken together, altered neuronal electrophysiological properties and astrogliosis could contribute to the neurological complications induced by AKI, and EPO offers hope as a potential neuroprotective agent. © 2021 Elsevier Inc

Hyperexcitability of VTA dopaminergic neurons in male offspring exposed to physical or psychological prenatal stress

Prenatal stress (PS) exposure leads to cognitive and behavioral alterations in offspring including an increased risk of substance abuse and anxiety disorders. Signalling from dopamine (DA) neurons of the ventral tegmental area (VTA) in the mesoaccumbal and mesocortical pathways plays a vital role in drug dependency and anxiety behavior. To provide further knowledge about the changes in drug seeking behavior and anxiety behaviors in prenatally stressed mice, we conducted ex vivo investigations in VTA brain slices of adult male PS offspring to evaluate the effects of two types of PS (physical vs. psychological) on activity of DA neurons. Elevated plus maze (EPM) was used to assess anxiety-like behaviors and conditioned place preference (CPP) was used to evaluate drug reinforcing effects in mice. An increased anxiety-like behavior and preference to morphine was observed in prenatally stressed mice. PS VTA DA cells exhibited greater Ih current and a higher frequency and amplitude of sEPSCs, which were consistent with a greater degree of pre- or postsynaptic excitability of the VTA. This was confirmed by lower rheobase and lower firing thresholds in PS VTA neurons, as well as increases in spontaneous firing frequency. When taken together, these data suggest that alterations in VTA DA neurons in this mouse model of prenatal stress might be associated with later life alterations in drug seeking and anxiety-like behaviors through their role in mesocortical and mesoaccumbal pathways. © 2020 Elsevier Inc

Affective dimensions of pain and region -specific involvement of nitric oxide in the development of empathic hyperalgesia

Empathy for pain depends on the ability to feel, recognize, comprehend and share painful emotional conditions of others. In this study, we investigated the role of NO in a rat model of empathic pain. Pain was socially transferred from the sibling demonstrator (SD) who experienced five formalin injection to the naïve sibling observer (SO) through observation. SO rats received L-NAME (a nonspecific NO synthase inhibitor) or L-arginine (a precursor of NO) prior to observing the SD. Nociception, and concentrations of NO metabolites (NOx) in the serum, left and right hippocampus, prefrontal cortex, and cerebellum were evaluated. Nociceptive responses were significantly increased in the pain-observing groups. NOx levels measured 24 h after the last pain observation using the Griess method, were indicative of NOx concentration decreases and increases in the left hippocampus and cerebellum, respectively. There was an increase in tissue concentration of NOx in cerebellum and prefrontal cortex in both pain and observer groups 7 days after the fifth formalin injection. Our results suggest that NO is involved in development of empathic hyperalgesia, and observation of sibling�s pain can change NO metabolites in different brain regions in observer rats. © 2020, The Author(s)

Looking into a Deluded Brain through a Neuroimaging Lens

Delusions are irrational, tenacious, and incorrigible false beliefs that are the most common symptom of a range of brain disorders including schizophrenia, Alzheimer�s, and Parkinson�s disease. In the case of schizophrenia and other primary delusional disorders, their appearance is often how the disorder is first detected and can be sufficient for diagnosis. At this time, not much is known about the brain dysfunctions leading to delusions, and hindering our understanding is that the complexity of the nature of delusions, and their very unique relevance to the human experience has hampered elucidation of their underlying neurobiology using either patients or animal models. Advances in neuroimaging along with improved psychiatric and cognitive modeling offers us a new opportunity to look with more investigative power into the deluded brain. In this article, based on data obtained from neuroimaging studies, we have attempted to draw a picture of the neural networks involved when delusion is present and evaluate whether different manifestations of delusions engage different regions of the brain. © The Author(s) 2020

Estrogen attenuates physical and psychological stress-induced cognitive impairments in ovariectomized rats

Introduction: Women are more vulnerable to stress-related disorders than men, which is counterintuitive as female sex hormones, especially estrogen, have been shown to be protective against stress disorders. Methods: In this study, we investigated whether two different models of stress act differently on ovariectomized (OVX) rats and the impact of estrogen on physical or psychological stress-induced impairments in cognitive-behaviors. Adult female Wistar rats at 21�22 weeks of age were utilized for this investigation. Sham and OVX rats were subjected to physical and psychological stress for 1 hr/day for 7 days, and cognitive performance was assessed using morris water maze (MWM) and passive avoidance (PA) tests. The open field and elevated plus maze tests (EPM) evaluated exploratory and anxiety-like behaviors. Results: In sham and OVX rats, both physical and psychological stressors were associated with an increase in EPM-determined anxiety-like behavior. OVX rats exhibited decreased explorative behavior in comparison with nonstressed sham rats (p <.05). Both physical stress and psychological stress resulted in disrupted spatial cognition as assayed in the MWM (p <.05) and impaired learning and memory as determined by the PA test when the OVX and sham groups were compared with the nonstressed sham group. Estrogen increased explorative behavior, learning and memory (p <.05), and decreased anxiety-like behavior compared with vehicle in OVX rats exposed to either type of stressor. Conclusions: When taken together, estrogen and both stressors had opposite effects on memory, anxiety, and PA performance in a rat model of menopause, which has important implications for potential protective effects of estrogen in postmenopausal women exposed to chronic stress. © 2021 The Authors. Brain and Behavior published by Wiley Periodicals LL