Microglial activating transcription factor 3 upregulation: An indirect target to attenuate inflammation in the nervous system.

Activating Transcription Factor 3 (ATF3) is upregulated in reaction to several cellular stressors found in a wide range of pathological conditions to coordinate a transcriptional response. ATF3 was first implicated in the transcriptional reaction to axotomy when its massive upregulation was measured in sensory and motor neuron cell bodies following peripheral nerve injury. It has since been shown to be critical for successful axon regeneration in the peripheral nervous system and a promising target to mitigate regenerative failure in the central nervous system.

Systemic hypoxia mimicry enhances axonal regeneration and functional recovery following peripheral nerve injury.

Despite the ability of peripheral nerves to regenerate after injury, failure occurs due to an inability of supporting cells to maintain growth, resulting in long-term consequences such as sensorimotor dysfunction and neuropathic pain. Here, we investigate the potential of engaging the cellular adaptive response to hypoxia, via inhibiting its negative regulators, to enhance the regenerative process. Under normoxic conditions, prolyl hydroxylase domain (PHD) proteins 1, 2, and 3 hydroxylate the key metabolic regulator hypoxia inducible factor 1α (HIF1α), marking it for subsequent proteasomal degradation.

An ATF3-CreERT2 Knock-In Mouse for Axotomy-Induced Genetic Editing: Proof of Principle.

Genome editing techniques have facilitated significant advances in our understanding of fundamental biological processes, and the Cre-Lox system has been instrumental in these achievements. Driving Cre expression specifically in injured neurons has not been previously possible: we sought to address this limitation in mice using a Cre-ERT2 construct driven by a reliable indicator of axotomy, activating transcription factor 3 (ATF3). When crossed with reporter mice, a significant amount of recombination was achieved (without tamoxifen treatment) in peripherally-projecting sensory, sympathetic, and motoneurons after peripheral nerve crush in hemizygotes (65-80% by 16 d) and was absent in uninjured neurons.

Preserved Adrenal Function After Lumbar Spinal Cord Transection Augments Low Pressure Bladder Activity in the Rat.

Spinal cord injury (SCI) disconnects supraspinal micturition centers from the lower urinary tract resulting in immediate and long-term changes in bladder structure and function. While cervical and high thoracic SCI have a greater range of systemic effects, clinical data suggest that those with lower (suprasacral) injuries develop poorer bladder outcomes. Here we assess the impact of SCI level on acute changes in bladder activity.