Experimental Chronic Prostatitis/Chronic Pelvic Pain Syndrome Increases Anxiety-Like Behavior: The Role of Brain Oxidative Stress, Serum Corticosterone, and Hippocampal Parvalbumin-Positive Interneurons

Abstract

Mechanisms of the brain-related comorbidities in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) are still largely unknown, although CP/CPPS is one of the major urological problems in middle-aged men, while these neuropsychological incapacities considerably diminish life quality. The objectives of this study were to assess behavioral patterns in rats with CP/CPPS and to determine whether these patterns depend on alterations in the brain oxidative stress, corticosterone, and hippocampal parvalbumin-positive (PV+) interneurons. Adult male Wistar albino rats from CP/CPPS (intraprostatic injection of 3% λ-carrageenan, day 0) and sham (0.9% NaCl) groups were subjected to pain and anxiety-like behavior tests (days 2, 3, and 7). Afterwards, rats were sacrificed and biochemical and immunohistochemical analyses were performed. Scrotal allodynia and prostatitis were proven in CP/CPPS, but not in sham rats. Ethological tests (open field, elevated plus maze, and light/dark tests) revealed significantly increased anxiety-like behavior in rats with CP/CPPS comparing to their sham-operated mates starting from day 3, and there were significant intercorrelations among parameters of these tests. Increased oxidative stress in the hippocampus, thalamus, and cerebral cortex, as well as increased serum corticosterone levels and decreased number of hippocampal PV+ neurons, was shown in CP/CPPS rats, compared to sham rats. Increased anxiety-like behavior in CP/CPPS rats was significantly correlated with these brain biochemical and hippocampal immunohistochemical alterations. Therefore, the potential mechanisms of observed behavioral alterations in CP/CPPS rats could be the result of an interplay between increased brain oxidative stress, elevated serum corticosterone level, and loss of hippocampal PV+ interneurons.

Effects of Polyphenols on Oxidative Stress, Inflammation, and Interconnected Pathways during Spinal Cord Injury

“…In a recent study, Daverey and Agrawal showed that 10 μM of curcumin and riluzole protected astrocytes derived from the human spinal cord against oxidative stress via Nrf2/HO-1 signaling [227]. Previously, Jiang et al showed that curcumin in different concentrations (5,10,15,20, and 25 mM) for 2 h activated Nrf2 target genes in primary spinal cord astrocytes, attenuated the level of intracellular ROS, and decreased oxidative damage and mitochondrial dysfunction [228]. Additionally, i.v.…”

“…Previous reviews indicated the crucial role of oxidative stress and axonal dysregulations in the pathogenesis of Parkinson's disease [11], epilepsy [12], and some other NDDs [13]. Accordingly, cytokines [14], nitric oxide (NO), antioxidant response element (ARE) [15], and other oxidative stress/inflammatory mediators, as well as extrinsic dysregulated pathways, seem to be potential regulators of such pathological conditions. We have also previously provided the role of apoptosis and autophagy following SCI [3]; however, no focus has been yet done on the pivotal role of oxidative stress after SCI.…”

Anxiogenic Potential of Experimental Sleep Fragmentation Is Duration-Dependent and Mediated via Oxidative Stress State

“…Our hypothesis was based on the fact that the hippocampus, together with other circuits of the limbic system, amygdala, prefrontal cortex, and others is on the crossroad of fear, memory, and anxiety pathways and that PV+ interneuron inhibitory projects control anxiety [65,66]. Loss of the hippocampal neurons coupled with anxiety-related behavior has been demonstrated in other studies [30,67]. However, it should still be underlined that hippocampal PV + interneurons [68] are involved in the behavioral patterns, including fear and anxiety [69], although they do not influence the mechanism of sleep fragmentation-evoked anxietylike behavior.…”

Mechanism of Acupuncture and Moxibustion on Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Narrative Review of Animal Studies

“…Recent studies have fully shown that the mechanism of brain-related comorbidities of CP/CPPS is closely related to the brain. Sutulovic et al [ 56 ] showed that anxiety-like behavior in rats with CP/CPPS increased, and the potential mechanisms of observed behavioral alterations could result from an interplay between increased brain oxidative stress, elevated serum corticosterone level, and loss of hippocampal PV + interneurons. They [ 57 ] also showed that CP/CPPS increases susceptibility to lindane-induced seizures in rats associated with the increased level of IL-1 β and IL-6 in the cortex and thalamus.…”