The aryl hydrocarbon receptor agonist ITE reduces inflammation and urinary dysfunction in a mouse model of autoimmune prostatitis.

Objectives: Prostate inflammation is linked to lower urinary tract dysfunction and is a key factor in chronic prostatitis/chronic pelvic pain syndrome. Autoimmunity was recently identified as a driver of prostate inflammation. Agonists of the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, have been used to suppress autoimmunity in mouse models of colitis, rhinitis, and dermatitis, but whether AHR agonists suppress prostate autoimmunity has not been examined.

Skin Reinnervation by Collateral Sprouting Following Spared Nerve Injury in Mice.

Following peripheral nerve injury, denervated tissues can be reinnervated via regeneration of injured neurons or collateral sprouting of neighboring uninjured afferents into denervated territory. While there has been substantial focus on mechanisms underlying regeneration, collateral sprouting has received less attention. Here, we used immunohistochemistry and genetic neuronal labeling to define the subtype specificity of sprouting-mediated reinnervation of plantar hindpaw skin in the mouse spared nerve injury (SNI) model, in which productive regeneration cannot occur.

Scientific and Regulatory Policy Committee Technical Review: Biology and Pathology of Ganglia in Animal Species Used for Nonclinical Safety Testing.

Dorsal root ganglia (DRG), trigeminal ganglia (TG), other sensory ganglia, and autonomic ganglia may be injured by some test article classes, including anti-neoplastic chemotherapeutics, adeno-associated virus-based gene therapies, antisense oligonucleotides, nerve growth factor inhibitors, and aminoglycoside antibiotics. This article reviews ganglion anatomy, cytology, and pathology (emphasizing sensory ganglia) among common nonclinical species used in assessing product safety for such test articles (TAs). Principal histopathologic findings associated with sensory ganglion injury include neuron degeneration, necrosis, and/or loss; increased satellite glial cell and/or Schwann cell numbers; and leukocyte infiltration and/or inflammation.

Scientific and Regulatory Policy Committee Points to Consider: Sampling, Processing, Evaluation, Interpretation, and Reporting of Test Article-Related Ganglion Pathology for Nonclinical Toxicity Studies.

Certain biopharmaceutical products consistently affect dorsal root ganglia, trigeminal ganglia, and/or autonomic ganglia. Product classes targeting ganglia include antineoplastic chemotherapeutics, adeno-associated virus-based gene therapies, antisense oligonucleotides, and anti-nerve growth factor agents. This article outlines "points to consider" for sample collection, processing, evaluation, interpretation, and reporting of ganglion findings; these points are consistent with published best practices for peripheral nervous system evaluation in nonclinical toxicity studies.

Pulmonary lesions induced by SARS-CoV-2 infection in domestic cats.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease 2019, which ranges from fatal disease in some to mild or subclinical in most affected individuals. Many recovered human patients report persistent respiratory signs; however, lung disease in post-acute infection is poorly understood. Our objective was to describe histologic lung lesions and viral loads following experimental SARS-CoV-2 infection in 11 cats.

Astrocytes contribute to pain gating in the spinal cord.

Various pain therapies have been developed on the basis of the gate control theory of pain, which postulates that nonpainful sensory inputs mediated by large-diameter afferent fibers (Aβ-fibers) can attenuate noxious signals relayed to the brain. To date, this theory has focused only on neuronal mechanisms. Here, we identified an unprecedented function of astrocytes in the gating of nociceptive signals transmitted by neurokinin 1 receptor–positive (NK1R) projection neurons in the spinal cord.

Protective Immunity and Persistent Lung Sequelae in Domestic Cats after SARS-CoV-2 Infection.

Severe acute respiratory syndrome coronavirus 2 readily transmits between domestic cats. We found that domestic cats that recover from an initial infection might be protected from reinfection. However, we found long-term persistence of inflammation and other lung lesions after infection, despite a lack of clinical symptoms and limited viral replication in the lungs.

Revisiting PNS Plasticity: How Uninjured Sensory Afferents Promote Neuropathic Pain.

Despite the widespread study of how injured nerves contribute to chronic pain, there are still major gaps in our understanding of pain mechanisms. This is particularly true of pain resulting from nerve injury, or neuropathic pain, wherein tactile or thermal stimuli cause painful responses that are particularly difficult to treat with existing therapies. Curiously, this stimulus-driven pain relies upon intact, uninjured sensory neurons that transmit the signals that are ultimately sensed as painful.

and lactational 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD) exposure exacerbates urinary dysfunction in hormone-treated C57BL/6J mice through a non-malignant mechanism involving proteomic changes in the prostate that differ from those elicited by testosterone and estradiol.

A recent study directed new focus on the fetal and neonatal environment as a risk factor for urinary dysfunction in aging males. Male mice were exposed and via lactation (IUL) to the persistent environmental contaminant 2,3,7,8-tetrachlorodibenzo--dioxin (TCDD) and then administered slow-release, subcutaneous implants of testosterone and estradiol (T+E2) as adults to mimic the hormonal environment of aging men. IUL TCDD exposure worsened T+E2-induced voiding dysfunction.

Functional Anatomy of the Sensory Nervous System: Updates From the Neuroscience Bench.

The simple tripartite classification of sensory neurons as A-beta, A-delta, and C fibers fails to convey the complexity of the neurons that encode stimuli as diverse as the texture of a surface, the location of a pinprick, or the direction of hair movement as a breeze moves across the skin. It has also proven to be inadequate when investigating the molecular mechanisms underlying pain, which can encompass any combination of chemical, tactile, and thermal modalities. Beginning with a brief overview of visceral and sensory neuroanatomy, this review expands upon sensory innervation of the skin as a prime example of the heterogeneity and complexity of the somatosensory nervous system.

RANAVIRUS EPIZOOTIC IN CAPTIVE EASTERN BOX TURTLES (TERRAPENE CAROLINA CAROLINA) WITH CONCURRENT HERPESVIRUS AND MYCOPLASMA INFECTION: MANAGEMENT AND MONITORING.

Frog virus 3 (FV3) and FV3-like viruses are members of the genus Ranavirus (family Iridoviridae) and are becoming recognized as significant pathogens of eastern box turtles (Terrapene carolina carolina) in North America. In July 2011, 5 turtles from a group of 27 in Maryland, USA, presented dead or lethargic with what was later diagnosed as fibrinonecrotic stomatitis and cloacitis. The presence of FV3-like virus and herpesvirus was detected by polymerase chain reaction (PCR) in the tested index cases.

Pet-1 Switches Transcriptional Targets Postnatally to Regulate Maturation of Serotonin Neuron Excitability.

Unlabelled: Newborn neurons enter an extended maturation stage, during which they acquire excitability characteristics crucial for development of presynaptic and postsynaptic connectivity. In contrast to earlier specification programs, little is known about the regulatory mechanisms that control neuronal maturation. The Pet-1 ETS (E26 transformation-specific) factor is continuously expressed in serotonin (5-HT) neurons and initially acts in postmitotic precursors to control acquisition of 5-HT transmitter identity.

Social stress alters inhibitory synaptic input to distinct subpopulations of raphe serotonin neurons.

Anxiety disorders are among the most prevalent psychiatric disorders, yet much is unknown about the underlying mechanisms. The dorsal raphe (DR) is at the crux of the anxiety-inducing effects of uncontrollable stress, a key component of models of anxiety. Though DR serotonin (5-HT) neurons play a prominent role, anxiety-associated changes in the physiology of 5-HT neurons remain poorly understood.

Glutamatergic input is selectively increased in dorsal raphe subfield 5-HT neurons: role of morphology, topography and selective innervation.

Characterization of glutamatergic input to dorsal raphe (DR) serotonin (5-HT) neurons is crucial for understanding how the glutamate and 5-HT systems interact in psychiatric disorders. Markers of glutamatergic terminals, vGlut1, 2 and 3, reflect inputs from specific forebrain and midbrain regions. Punctate staining of vGlut2 was homogeneous throughout the mouse DR whereas vGlut1 and vGlut3 puncta were less dense in the lateral wing (lwDR) compared with the ventromedial (vmDR) subregion.

The presynaptic component of the serotonergic system is required for clozapine's efficacy.

Clozapine, by virtue of its absence of extrapyramidal side effects and greater efficacy, revolutionized the treatment of schizophrenia, although the mechanisms underlying this exceptional activity remain controversial. Combining an unbiased cheminformatics and physical screening approach, we evaluated clozapine's activity at >2350 distinct molecular targets. Clozapine, and the closely related atypical antipsychotic drug olanzapine, interacted potently with a unique spectrum of molecular targets.

Increased intrinsic excitability of lateral wing serotonin neurons of the dorsal raphe: a mechanism for selective activation in stress circuits.

The primary center of serotonin (5-HT) projections to the forebrain is the dorsal raphe nucleus (DR), a region known for its role in the limbic stress response. The ventromedial subregion of the DR (vmDR) has the highest density of 5-HT neurons and is the major target in experiments that involve the DR. However, studies have demonstrated that a variety of stressors induce activation of neurons that is highest in the lateral wing subregion (lwDR) and includes activation of lwDR 5-HT neurons.

Serotonergic transcriptional programming determines maternal behavior and offspring survival.

Central serotonergic signaling influences many physiological processes, but a requirement for reproductive success has not been demonstrated. Using mouse dams with a specific disruption in serotonin neuron development, we found that serotonergic function is required for the nurturing and survival of offspring. Full rescue of survival depended on the mother's expression level of the upstream serotonergic transcriptional cascade.