Differential effects of exercise and hormone treatment on spinal cord injury-induced changes in micturition and morphology of external urethral sphincter motoneurons.

Background: Spinal cord injury (SCI) results in lesions that destroy tissue and spinal tracts, leading to deficits in locomotor and autonomic function. We have previously shown that after SCI, surviving motoneurons innervating hindlimb muscles exhibit extensive dendritic atrophy, which can be attenuated by treadmill training or treatment with gonadal hormones post-injury. We have also shown that following SCI, both exercise and treatment with gonadal hormones improve urinary function.

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains.

JOURNAL/nrgr/04.03/01300535-202509000-00028/figure1/v/2024-11-05T132919Z/r/image-tiff Successful polyethylene glycol fusion (PEG-fusion) of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to: (1) rapidly restore electrophysiological continuity; (2) prevent distal Wallerian Degeneration and maintain their myelin sheaths; (3) promote primarily motor, voluntary behavioral recoveries as assessed by the Sciatic Functional Index; and, (4) rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex (e.g.

Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord.

JOURNAL/nrgr/04.03/01300535-202507000-00030/figure1/v/2024-09-09T124005Z/r/image-tiff Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions; behavioral recovery is typically poor. We used a plasmalemmal fusogen, polyethylene glycol (PEG), to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic nerves.

A "Four Core Genotypes" rat model to distinguish mechanisms underlying sex-biased phenotypes and diseases.

Background: We have generated a rat model similar to the Four Core Genotypes mouse model, allowing comparison of XX and XY rats with the same type of gonad. The model detects novel sex chromosome effects (XX vs. XY) that contribute to sex differences in any rat phenotype.

EMG Testing throughout behavioral recovery after rat sciatic nerve crush injury results in exuberant motoneuron dendritic hypertrophy.

Background: Peripheral nerve injury (PNI) is the most common type of nerve trauma yet, while injured motoneurons exhibit a robust capacity for regeneration, behavioral recovery is protracted and typically poor. Neurotherapeutic approaches to PNI and repair have primarily focused on the enhancement of axonal regeneration, in terms of rate, axonal sprouting, and reconnection connectivity. Both electrical stimulation (ES) and treatment with androgens [e.

Intraneural Topography of Rat Sciatic Axons: Implications for Polyethylene Glycol Fusion Peripheral Nerve Repair.

Peripheral nerve injuries are the most common type of nerve trauma. We have been working with a novel repair technique using a plasmalemmal fusogen, polyethylene glycol (PEG), to re-fuse the membranes of severed axons. PEG-fusion repair allows for immediate re-innervation of distal targets, prevents axonal degeneration, and improves behavioral recovery.

Exercise is neuroprotective on the morphology of somatic motoneurons following the death of neighboring motoneurons via androgen action at the target muscle.

Motoneuron loss is a severe medical problem that can result in loss of motor control and eventually death. We have previously demonstrated that partial motoneuron loss can result in dendritic atrophy and functional deficits in nearby surviving motoneurons, and that an androgen-dependent effect of exercise following injury can be neuroprotective against this dendritic atrophy. In this study, we explored where the necessary site of androgen action is for exercise-driven neuroprotective effects on induced dendritic atrophy.

Exercise promotes recovery after motoneuron injury via hormonal mechanisms.

Injuries to spinal motoneurons manifest in a variety of forms, including damage to peripheral axons, neurodegenerative disease, or direct insult centrally. Such injuries produce a variety of negative structural and functional changes in both the directly affected and neighboring motoneurons. Exercise is a relatively simple behavioral intervention that has been demonstrated to protect against, and accelerate recovery from, these negative changes.

Behavioral recovery and spinal motoneuron remodeling after polyethylene glycol fusion repair of singly cut and ablated sciatic nerves.

Polyethylene glycol repair (PEG-fusion) of severed sciatic axons restores their axoplasmic and membrane continuity, prevents Wallerian degeneration, maintains muscle fiber innervation, and greatly improves recovery of voluntary behaviors. We examined alterations in spinal connectivity and motoneuron dendritic morphology as one potential mechanism for improved behavioral function after PEG-fusion. At 2-112 days after a single-cut or allograft PEG-fusion repair of transected or ablated sciatic nerves, the number, size, location, and morphology of motoneurons projecting to the tibialis anterior muscle were assessed by retrograde labeling.

Neuroprotective Effects of Exercise on the Morphology of Somatic Motoneurons Following the Death of Neighboring Motoneurons.

. Motoneuron loss is a severe medical problem that can result in loss of motor control and eventually death. We have previously demonstrated that partial motoneuron loss can result in dendritic atrophy and functional deficits in nearby surviving motoneurons, and that treatment with androgens can be neuroprotective against this dendritic atrophy.

Gonadal hormones differentially regulate sex-specific stress effects on glia in the medial prefrontal cortex.

Women are more susceptible to various stress-linked psychopathologies, including depression. Dysfunction of the medial prefrontal cortex (mPFC) has been implicated in depression, and studies indicate sex differences in stress effects on mPFC structure and function. For example, chronic stress induces dendritic atrophy in the mPFC in male rats, yet dendritic growth in females.

Polyethylene glycol (PEG) and other bioactive solutions with neurorrhaphy for rapid and dramatic repair of peripheral nerve lesions by PEG-fusion.

Background: Nervous system injuries in mammals often involve transection or segmental loss of peripheral nerves. Such injuries result in functional (behavioral) deficits poorly restored by naturally occurring 1-2 mm/d axonal outgrowths aided by primary repair or reconstruction. "Neurorrhaphy" or nerve repair joins severed connective tissues, but not severed cytoplasmic/plasmalemmal extensions (axons) within the tissue.

Neuroprotective Effects on the Morphology of Somatic Motoneurons Following the Death of Neighboring Motoneurons: A Role for Microglia?

Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone protects motoneurons from induced dendritic atrophy. We explored a potential mechanism for this induced atrophy and protection by testosterone, examining the microglial response to partial depletion of motoneurons. Motoneurons innervating the vastus medialis muscles of adult male rats were killed by intramuscular injection of cholera toxin-conjugated saporin; some saporin-injected rats were treated with testosterone.

Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery.

Retrogradely-transported neurotrophin signaling plays an important role in regulating neural circuit specificity. Here we investigated whether targeted delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic patterning and synapse formation of the lumbar MNs. , Adeno-associated virus serotype two overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and neurite outgrowth in cultured spinal cord neurons.

Protective effects of gonadal hormones on spinal motoneurons following spinal cord injury.

Spinal cord injury (SCI) results in lesions that destroy tissue and disrupt spinal tracts, producing deficits in locomotor and autonomic function. The majority of treatment strategies after SCI have concentrated on the damaged spinal cord, for example working to reduce lesion size or spread, or encouraging regrowth of severed descending axonal projections through the lesion, hoping to re-establish synaptic connectivity with caudal targets. In our work, we have focused on a novel target for treatment after SCI, surviving spinal motoneurons and their target musculature, with the hope of developing effective treatments to preserve or restore lost function following SCI.

Polyethylene glycol solutions rapidly restore and maintain axonal continuity, neuromuscular structures, and behaviors lost after sciatic nerve transections in female rats.

Complete severance of major peripheral mixed sensory-motor nerve proximally in a mammalian limb produces immediate loss of action potential conduction and voluntary behaviors mediated by the severed distal axonal segments. These severed distal segments undergo Wallerian degeneration within days. Denervated muscles atrophy within weeks.

Polyethylene glycol treated allografts not tissue matched nor immunosuppressed rapidly repair sciatic nerve gaps, maintain neuromuscular functions, and restore voluntary behaviors in female rats.

Many publications report that ablations of segments of peripheral nerves produce the following unfortunate results: (1) Immediate loss of sensory signaling and motor control; (2) rapid Wallerian degeneration of severed distal axons within days; (3) muscle atrophy within weeks; (4) poor behavioral (functional) recovery after many months, if ever, by slowly-regenerating (∼1mm/d) axon outgrowths from surviving proximal nerve stumps; and (5) Nerve allografts to repair gap injuries are rejected, often even if tissue matched and immunosuppressed. In contrast, using a female rat sciatic nerve model system, we report that neurorrhaphy of allografts plus a well-specified-sequence of solutions (one containing polyethylene glycol: PEG) successfully addresses each of these problems by: (a) Reestablishing axonal continuity/signaling within minutes by nonspecific ally PEG-fusing (connecting) severed motor and sensory axons across each anastomosis; (b) preventing Wallerian degeneration by maintaining many distal segments of inappropriately-reconnected, PEG-fused axons that continuously activate nerve-muscle junctions; (c) maintaining innervation of muscle fibers that undergo much less atrophy than otherwise-denervated muscle fibers; (d) inducing remarkable behavioral recovery to near-unoperated levels within days to weeks, almost certainly by CNS and PNS plasticities well-beyond what most neuroscientists currently imagine; and (e) preventing rejection of PEG-fused donor nerve allografts with no tissue matching or immunosuppression. Similar behavioral results are produced by PEG-fused autografts.

Conundrums and confusions regarding how polyethylene glycol-fusion produces excellent behavioral recovery after peripheral nerve injuries.

Current Neuroscience dogma holds that transections or ablations of a segment of peripheral nerves produce: (1) Immediate loss of axonal continuity, sensory signaling, and motor control; (2) Wallerian rapid (1-3 days) degeneration of severed distal axons, muscle atrophy, and poor behavioral recovery after many months (if ever, after ablations) by slowly-regenerating (1 mm/d), proximal-stump outgrowths that must specifically reinnervate denervated targets; (3) Poor acceptance of microsutured nerve allografts, even if tissue-matched and immune-suppressed. Repair of transections/ablations by neurorrhaphy and well-specified-sequences of PEG-fusion solutions (one containing polyethylene glycol, PEG) successfully address these problems. However, conundrums and confusions regarding unorthodox and dramatic results of PEG-fusion repair in animal model systems often lead to misunderstandings.

Protective Effects of Estradiol and Dihydrotestosterone following Spinal Cord Injury.

Spinal cord injury (SCI) results in lesions that destroy tissue and disrupt spinal tracts, producing deficits in locomotor and autonomic function. We previously demonstrated that motoneurons and the muscles they innervate show pronounced atrophy after SCI, and these changes are prevented by treatment with testosterone. Here, we assessed whether the testosterone active metabolites estradiol and dihydrotestosterone have similar protective effects after SCI.

Hormonal Treatment Effects on the Cross-sectional Area of Pubococcygeus Muscle Fibers After Denervation and Castration in Male Rats.

We explore the interaction of muscle innervation and gonadal hormone action in the pubococcygeus muscle (Pcm) after castration and hormone replacement. Male Wistar rats were castrated and the Pcm was unilaterally denervated; after 2 or 6 weeks, the cross-sectional area (CSA) of Pcm fibers was assessed. Additional groups of castrated rats were used to examine the effects of hormone replacement.

Neuroprotective effects of testosterone metabolites and dependency on receptor action on the morphology of somatic motoneurons following the death of neighboring motoneurons.

Partial depletion of spinal motoneuron populations induces dendritic atrophy in neighboring motoneurons, and treatment with testosterone is neuroprotective, attenuating induced dendritic atrophy. In this study we examined whether the protective effects of testosterone could be mediated via its androgenic or estrogenic metabolites. Furthermore, to assess whether these neuroprotective effects were mediated through steroid hormone receptors, we used receptor antagonists to attempt to prevent the neuroprotective effects of hormones after partial motoneuron depletion.

The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens.

Classic findings have demonstrated an important role for sex steroids as regulators of aggression, but this relationship is lacking within some environmental contexts. In mammals and birds, the adrenal androgen dehydroepiandrosterone (DHEA), a non-gonadal precursor of biologically active steroids, has been linked to aggression. Although females, like males, use aggression when competing for limited resources, the mechanisms underlying female aggression remain understudied.

Oxytocin increases VTA activation to infant and sexual stimuli in nulliparous and postpartum women.

After giving birth, women typically experience decreased sexual desire and increased responsiveness to infant stimuli. These postpartum changes may be viewed as a trade-off in reproductive interests, which could be due to alterations in brain activity including areas associated with reward. The goal of this study was to describe the roles of oxytocin and parity on reward area activation in response to reproductive stimuli, specifically infant and sexual images.