Breaking the links between ageism and health: An integrated perspective.

Ageism refers to prejudice, stereotypes or discrimination based on a person's actual or perceived chronological age. While ageism can affect people at all stages of the human lifespan, ageism against older adults has emerged as the most pervasive and potentially harmful. Much is now understood about how ageism can impact older people's health and wellbeing via structural, organisational, and provider level biases that threaten the provision of equitable and ethical healthcare. Negative attitudes about age and ageing also contribute to workforce shortages in aged care sectors, such as residential aged care and nursing. However, often underappreciated is how self-directed ageism, which refers to ageism turned against oneself, can also be an important determinant of health and wellbeing. Relative to external sources of ageism, negative internalised ageist beliefs are not only experienced more frequently in older adults' everyday lives, but are also more strongly linked to their health and wellbeing. Here we highlight how this understanding means that eliminating ageism requires a multifaceted approach that targets not only health care systems and aged care professionals, but older people themselves. Because normal age-related cognitive changes in how we think, perceive and reason increase the risk of older people viewing themselves through a negative and ageist lens, we provide a novel discussion of how broader insights from cognitive ageing literature must play a central role in any agenda focused on breaking the links between ageism and health.

Oral health-related quality of life is more strongly correlated with mental health than with oral health in relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a leading cause of neurological disability in young and middle-aged populations, associated with substantial burden of illness. Because a growing literature now shows that this burden extends to poorer oral health, oral health-related quality of life (OHRQoL) may be reduced as well. OBJECTIVES: To test whether people with relapsing-remitting MS (RRMS) have poorer OHRQoL than demographically matched controls, and to establish which variables are associated with worse OHRQoL. MATERIALS AND METHODS: In total, 64 people with RRMS and 69 demographically matched controls participated. Both groups completed the Oral Health Impact Profile (OHIP-14), a validated measure of OHRQoL, as well as an objective oral health examination performed by a qualified dentist, a measure of dental-related functionality and a measure of mental health. RESULTS: OHRQoL was significantly poorer in the RRMS relative to the control group. However, although poorer OHRQoL in the RRMS group was moderately associated with objectively assessed oral health (r = .30), it was more strongly associated with mental health (r = .61). For the control group, the reverse pattern of association was evident, with OHRQoL more strongly associated with oral health (r = .48) relative to mental health (r = .20). CONCLUSION: People with RRMS report poorer OHRQoL than demographically matched controls, but these appraisals are more strongly linked to mental health than to objective oral health indicators.

Dental anxiety and oral health following stroke: a pilot study.

BACKGROUND: Oral health is often poorer in people living with acquired brain injury relative to non-clinical controls. However, although anxiety disorders become more common following stroke, no study to date has tested whether dental anxiety might contribute to stroke survivors' increased vulnerability to poorer oral health. This pilot study reports the first test of whether the anxiety disturbances that commonly present following stroke extend to dental anxiety, and if dental anxiety in this group is linked to poorer oral health. MATERIALS AND METHODS: First-time stroke survivors (N = 35) and demographically matched controls (N = 35) completed validated measures of dental anxiety, oral health, negative affect, and life satisfaction. RESULTS: Stroke survivors did not differ from controls in their overall levels of dental anxiety or oral health, but uniquely for the stroke group, dental anxiety was strongly associated with poorer oral health, and this effect remained significant even after controlling for negative affect and life satisfaction. CONCLUSION: Stroke survivors who have higher levels of dental-related anxiety may be at increased risk of poorer oral health.

Memory decline in older individuals predicts an objective indicator of oral health: findings from the Sydney Memory and Ageing Study.

BACKGROUND: Growing evidence suggests that there is an association between poor oral health and cognitive function in late adulthood. However, most studies to date have relied on cross-sectional research methods that do not permit inferences about the temporality of any association. Moreover, the few longitudinal studies that do exist have typically relied on small samples and quite limited cognitive or oral health assessments. The aim of the present study was therefore designed to provide the first direct evaluation of whether cognitive function is predictive of poor oral health in older adults. METHODS: This longitudinal research included data from 339 participants aged 70 years or older from The Sydney Memory and Ageing Study (MAS), a large cohort of healthy community-dwelling older adults. Cognitive function was assessed using a battery of tests at baseline (Wave 1) in 2005 and six years later (Wave 4) in 2011. In 2015 (Wave 6), participants were assessed for oral health using the Oral Health Assessment Tool (OHAT), number of functional occluding pairs of natural teeth and sublingual resting saliva pH (SRSpH). Ordinal least squares regression analysis was used to model the effect of cognitive function on total OHAT score, and binomial logistic regression used for SRSpH and occluding pairs of functional teeth. RESULTS: Two models were tested. In the partially adjusted model, age, gender and years of education were included. The fully adjusted model additionally included medical conditions, general health, depression, smoking, alcohol consumption, functionality, and dental care utilization. The key finding to emerge was that a six-year change in memory (from Wave 1 to Wave 4) was associated with lower sublingual resting saliva pH at Wave 6 in partially (Odds Ratio (OR) = 0.65) and fully adjusted model (OR = 0.63). CONCLUSIONS: This longitudinal study provides further evidence that a relationship between cognitive function and oral health exists, and also points to this relationship potentially being bi-directional, as previous evidence suggests. The findings from the study also suggest that older adults who present with greater than normal memory decline at an earlier point in life were more likely to experience poor oral health when this was evaluated at a later time-point, four years later.

Cognitive function and oral health in relapsing-remitting multiple sclerosis.

OBJECTIVES: Multiple sclerosis (MS) is often associated with reduced cognitive function, and there is also emerging evidence of a heightened vulnerability to oral health problems. However, although links between cognitive function and oral health have been identified in other special populations, it remains to be established whether this relationship is also evident for people with MS. The aim of this study was to provide the first empirical test of whether there is a relationship between cognitive function and oral health in people diagnosed with relapsing-remitting multiple sclerosis (RRMS). METHODS: One hundred and eleven individuals were evaluated: 56 people diagnosed with RRMS and 55 demographically matched healthy controls. All participants completed an objective oral health assessment as well as a standardized battery that assessed six distinct neurocognitive domains. RESULTS: Relative to controls, people with RRMS presented with higher rates of decayed teeth and mild gingivitis, and also performed more poorly in three of the six neurocognitive domains assessed (language, complex attention, and executive function). However, for the RRMS group, no associations emerged between oral health with performance on any of the six neurocognitive domains. CONCLUSIONS: These data cross-validate previous research which shows people with RRMS are more likely to present with both reduced cognitive function and poorer oral health, but also extends this literature in a meaningful way by additionally showing for the first time that these clinical features are unrelated in RRMS. CLINICAL RELEVANCE: The findings emphasize the need for early assessment of both oral health and cognitive function in people with RRMS so that appropriate interventions and support can be put in place for each of these clinical symptoms.

Episodic foresight in multiple sclerosis.

OBJECTIVE: Episodic foresight refers to the ability to imagine future scenarios and to then use this imaginative capacity to guide future-directed behavior. Multiple sclerosis (MS) is associated with deficits generating the phenomenological characteristics of future events (the imaginative component of episodic foresight), but no study to date has tested whether MS is also associated with deficits using episodic foresight to appropriately guide future-directed behavior. METHOD: Forty people with relapsing-remitting MS (RRMS) and 40 demographically matched healthy participants completed a validated measure that met strict criteria for assessing the functional application of episodic foresight, Virtual-Week Foresight (VW-Foresight). RESULTS: Overall, people with RRMS did not differ significantly relative to comparison participants in how likely they were to spontaneously acquire items that would later allow a problem to be solved and were also just as likely to subsequently use these items to solve the problem. However, the latter group difference was large in magnitude and just failed to attain significance. Higher levels of depression were significantly related to performance on this same "use" component of foresight in the RRMS group, and depressed RRMS participants were significantly impaired in this aspect of foresight relative to both healthy participants and nondepressed RRMS participants. The depressed MS subgroup also differed from the nondepressed subgroup in their ability to perform instrumental activities of daily living. CONCLUSIONS: People with RRMS who present with heightened levels of depressive symptomatology also appear to be at greater risk of experiencing specific problems with episodic foresight. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Event-Based but Not Time-Based Prospective Memory Is Related to Oral Health in Late Adulthood.

BACKGROUND: Most evidence now indicates that cognitive function is related to poorer oral health in late adulthood, but that this relationship is not invariant across specific cognitive domains. Prospective memory (PM) is a core memory skill that refers to memory for future intentions and is known to be related to the formation of habits such as tooth flossing. However, the relationship between PM and oral health has been subject to only limited empirical study. OBJECTIVE: The two studies reported in this paper were designed to test whether PM is related to oral health in older adults of varying vulnerability status. METHODS: Study 1 sampled community-dwelling older adults (N = 172) living independently in the community; Study 2 sampled older adults living in a retirement village (N = 32). Participants in both studies were asked to complete a behavioural measure of PM, with their oral health indexed via self-report (Study 1) or an objective oral health exam (Study 2). RESULTS: In both studies, relationships emerged between event-based PM and oral health, with Study 2 showing that these relationships were specific to oral health measures of plaque and calculus. CONCLUSIONS: Older adults are particularly vulnerable to dental pathology, with important implications for their broader health and well-being. By showing that there is a relationship between oral health and a particular type of PM, this work will have potential implications for the development of more effective interventions focused on enhancing oral health outcomes in this group, such as those focused on strengthening habit formation.

Can chronic oral inflammation and masticatory dysfunction contribute to cognitive impairment?

PURPOSE OF REVIEW: This article provides an overview of current literature focused on oral health and cognitive impairment in older adulthood, focusing in particular on whether oral inflammation, tooth loss and masticatory dysfunction might increase the risk of cognitive impairment in this age group. RECENT FINDINGS: There is now general acceptance that cognitive impairment contributes to poor oral health, largely through detrimental changes in behaviours related to maintaining good oral hygiene. There is more limited evidence for the reverse causal direction, but at least some studies now suggest that inflammatory mechanisms, tooth loss and masticatory dysfunction each have the potential to contribute to cognitive decline. SUMMARY: Poorer oral health significantly correlates with cognitive dysfunction, and at least some studies suggest that there may be a bi-directional causal relationship. Randomized controlled trials assessing cognitive abilities in relation to oral hygiene or oral health interventions, or provision of removable or fixed (implant-supported) dentures, are encouraged.

A systematic review of oral health in people with multiple sclerosis.

OBJECTIVES: Despite more than 25 years of research focused on this topic, it remains unclear whether people with multiple sclerosis are more likely to present with oral health problems. The aim of this study was to provide the first systematic review of this literature. METHODS: A literature search for studies focused on oral health and multiple sclerosis was conducted using PRISMA guidelines. Electronic databases (PubMed, Scopus, Web of Science, MEDLINE and CINAHL) were searched up until February 2019. Two independent coders extracted data, and study quality graded using the Newcastle-Ottawa Scale (NOS). RESULTS: From 1281 articles identified, 17 met all the eligibility criteria. Of the seventeen studies, more than half included a nonclinical control group, and the majority were observational studies. The included studies were of poor to moderate quality. Taken together, the results provided only very limited evidence that people with multiple sclerosis are more likely to present with dental caries and gingival disease. There was suggestive evidence that people with multiple sclerosis may be at higher risk of periodontal disease and present with poorer oral hygiene, and moderate evidence for an association between multiple sclerosis and temporomandibular disorders. CONCLUSIONS: This systematic review provides evidence of an association between multiple sclerosis and at least some oral health problems. When temporomandibular disorders and periodontal status specifically have been assessed, most studies provide evidence of an association with multiple sclerosis. However, this review also clearly highlights the need for further, high-quality studies in this area.

An empirical study of how emotion dysregulation and social cognition relate to occupational burnout in dentistry.

Introduction Dentists are frequently exposed to occupational stressors, including emotionally tense interactions with patients who are experiencing pain, anxiety and fear. Unsurprisingly, dentists are also a group that experience particularly high levels of occupational burnout. The present study provides the first empirical test of whether occupational burnout is higher, and general wellbeing is lower, for dental practitioners and students who have greater difficulties managing their own emotions (emotion dysregulation) and detecting and interpreting social cues from others (social cognitive difficulties).Materials and methods Ninety-six dental practitioners and 54 dental students completed validated measures of emotion regulation, social cognitive function, occupational burnout and wellbeing.Results Consistent with broader literature, rates of burnout were significantly higher in both dental practitioners and students, relative to normative standards. Importantly, the results also identified significant associations between rates of burnout with both emotion dysregulation, as well as one of the measures of social cognitive function: the empathic disposition to experience discomfort in response to the distress of others (personal distress). Ratings of emotion dysregulation and personal distress were also significantly higher for dental students relative to practitioners.Conclusion These data highlight the importance of being able to effectively manage difficult emotions in the dental practice.

Oral Health and Cognitive Function in Older Adults: A Systematic Review.

BACKGROUND: It has often been argued that there is a relationship between oral health and cognitive decline in late adulthood, but a recent systematic review concluded that it was unclear "how or whether" any relationship exists. However, most of the studies that contributed to this review operationalised cognitive function using a brief cognitive screen and/or dementia status. OBJECTIVE: An updated systematic review was conducted that focused on how oral health relates to specific cognitive abilities in older adults (specifically, the neurocognitive domains specified in the DSM-5: learning and memory, perceptual motor function, language, executive function, complex attention, and social cognition). METHODS: A systematic review was undertaken and completed in August 2018. From a total of 1,304 potentially relevant articles, 23 were identified that assessed oral health and at least one of the specific cognitive domains in an older adult cohort. RESULTS: The most consistent relationships were identified with learning and memory, complex attention, and executive function. For each of these cognitive domains, most studies identified significant unadjusted associations with oral health; where adjustments for covariates were made, at least one of the associations with oral health remained significant in half or more of the studies. Results were less clear for the domains of language and perceptual motor function. No study assessed the relationship between social cognition and oral health. CONCLUSIONS: This systematic review provides evidence of an association between learning and memory, complex attention, and executive function with oral health in old age. Gaining a detailed picture of how specific types of cognitive decline relate to oral health has potential implications for earlier identification of older adults who experience oral health problems, and may also inform the development of more effective interventions focused on enhancing oral health outcomes in this group.

Intact spontaneous emotional expressivity to non-facial but not facial stimuli in schizophrenia: An electromyographic study.

Emotional stimuli, such as facial expressions, reliably evoke rapid, spontaneous and covert facial reactions in the perceiver that reflect the affective valence of the observed stimulus. These physiological reactions have been linked to a variety of social cognitive processes known to be disrupted in schizophrenia, such as emotion recognition and affective empathy. Moreover, individuals with schizophrenia exhibit atypical rapid facial reactions when observing emotional expressions. The current study aimed to determine if the disruption in schizophrenia is specific to facial expressions, or instead reflects more generalised emotional or motor impairments in the elicitation of this rapid facial response. Here we quantified activity in the corrugator supercilii and zygomaticus major muscle regions using electromyography while individuals with schizophrenia (n = 24) and controls (n = 21) viewed images of facial and non-facial emotional stimuli. The results indicate that schizophrenia is marked by a disruption in rapid facial responding to facial expressions, but intact responding to non-facial emotional stimuli. This dissociation between the processing of facial and non-facial emotional stimuli points to the need for a greater understanding of the degree to which facial emotion processing impairments contribute to disruptions in mimetic responding in this population.

Age invariance in rapid facial affective reactions to emotionally valenced stimuli.

It has been suggested that an age-related positivity effect may only occur in the context of explicit information processing, but it is unclear whether this bias extends to the processing of rapid facial reactions. In addition, most studies that have looked for evidence of age-related implicit positivity have used attentional (as opposed to sensory) unawareness paradigms, or used broad-based indicators of attentional awareness that do not speak to the nature of the affective response. In the present study, younger and older adults were therefore asked to view non-facial images presented supraliminally (i.e., consciously) as well as outside of sensory awareness (i.e., subliminally) while their facial reactions were indexed using electromyography. The results indicated that both younger and older adults exhibited rapid facial reactions congruent with the emotional valence of non-facial images in both supraliminal and subliminal conditions. Relative to young, older adults did not respond with greater zygomaticus (cheek) activity to positive stimuli or reduced corrugator (brow) activity to negative stimuli in either condition. These data show that rapid facial reactions to emotional stimuli are intact in late adulthood, even in response to stimuli that activate more automatic and implicit forms of emotion processing. However, there is no evidence for any age-related positivity bias in these behavioral responses.

Age and the experience of strong self-conscious emotion.

OBJECTIVES: It remains unclear whether there are age-related changes in the experience of strong self-conscious emotion, such as shame, guilt, pride and embarrassment. Because shame and guilt figure prominently in the aetiology of depressive symptoms and other mental health problems, a better understanding of how age affects the strong experience of these two negative self-conscious emotions is of particular importance. METHODS: Thirty younger, 30 middle-aged and 30 older adults were compared on standardised cognitive assessments, in addition to an interview-based measure that assessed whether there are age differences in the likelihood of strongly experiencing four different types of self-conscious emotion within the past five years (shame, guilt, embarrassment and pride). RESULTS: The three groups did not differ in their likelihood of reporting an event that strongly elicited the positive self-conscious emotion of pride. However, older adults were more likely to report sources of pride that were other (as opposed to self) focused. Older adults were also less likely to report experiencing events that elicited all three negative self-conscious emotions, in particular, shame. CONCLUSIONS: Strong negative self-conscious emotion, and in particular shame, appears to be experienced less by older than younger adults.

Dual Delivery of NGF and bFGF Coacervater Ameliorates Diabetic Peripheral Neuropathy via Inhibiting Schwann Cells Apoptosis.

Diabetic neuropathy is a kind of insidious complications that impairs neural and vascular function and ultimately leads to somatic and visceral denervation. Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are important neurotrophic factors for stimulating angiogenesis and improving peripheral nerve function. Administrating a single factor has good therapeutic effect on diabetic peripheral neuropathy (DPN). However, the short half-life and rapid diffusion of growth factors under physiological conditions limits its clinical applications. Here, we used a biodegradable coacervate, composed of heparin and polycation, to dominate the combined release of bFGF and NGF in a steady fashion. We found this combined growth factors (GFs) coacervate, administered as a single injection, improved motor and sensory functions, restored morphometric structure and decreased apoptosis of Schwann cells in a rat model of prolonged DPN. Similarly the GFs coacervate, as compared with free bFGF and NGF combination, markedly reduced the apoptosis level of a rat Schwann cell line, RSC 96 cells in vitro. We also demonstrated that neuroprotective effects of the GFs coacervate in both rat DPN model and hyperglycemia-induced RSC 96 cell model is likely due to suppression of endocytoplasmic reticulum stress (ERS).

Single injection of a novel nerve growth factor coacervate improves structural and functional regeneration after sciatic nerve injury in adult rats.

The prototypical neurotrophin, nerve growth factor (NGF), plays an important role in the development and maintenance of many neurons in both the central and peripheral nervous systems, and can promote functional recovery after peripheral nerve injury in adulthood. However, repair of peripheral nerve defects is hampered by the short half-life of NGF in vivo, and treatment with either NGF alone or NGF contained in synthetic nerve conduits is inferior to the use of nerve autografts, the current gold standard. We tested the reparative ability of a single local injection of a polyvalent coacervate containing polycation-poly(ethylene argininylaspartate diglyceride; PEAD), heparin, and NGF, in adult rats following sciatic nerve crush injury, using molecular, histological and behavioral approaches. In vitro assays demonstrated that NGF was loaded into the coacervate at nearly 100% efficiency, and was protected from proteolytic degradation. In vivo, the coacervate enhanced NGF bioavailability, leading to a notable improvement in motor function (track walking analysis) after 30days. The NGF coacervate treatment was also associated with better weight gain and reduction in atrophy of the gastrocnemius muscle. Furthermore, light and electron microscopy showed that the number of myelinated axons and axon-to-fiber ratio (G-ratio) were significantly higher in NGF coacervate-treated rats compared with control groups. Expression of markers of neural tissue regeneration (MAP-2, S-100ß, MBP and GAP-43), as well as proliferating Schwann cells and myelin-axon relationships (GFAP and NF200), were also increased. These observations suggest that even a single administration of NGF coacervate could have therapeutic value for peripheral nerve regeneration and functional recovery.

Neurotrophic actions initiated by proNGF in adult sensory neurons may require peri-somatic glia to drive local cleavage to NGF.

The nerve growth factor (NGF) precursor, proNGF, is implicated in various neuropathological states. ProNGF signals apoptosis by forming a complex with the receptors p75 and sortilin, however, it can also induce neurite growth, proposed to be mediated by the receptor of mature NGF, tyrosine kinase receptor A (TrkA). The way in which these dual effects occur in adult neurons is unclear. We investigated the neurotrophic effects of proNGF on peptidergic sensory neurons isolated from adult mouse dorsal root ganglia and found that proNGF stimulated neurite extension and branching, requiring p75, sortilin and TrkA. Neurite growth rarely occurred in sortilin-expressing neurons but was commonly observed in TrkA-positive, sortilin-negative neurons that associated closely with sortilin-positive glia. ProNGF was unable to induce local trophic effects at growth cones where sortilin-positive glia was absent. We propose that in adult sensory neurons the neurotrophic response to proNGF is mediated by NGF and TrkA, and that peri-somatic glia may participate in sortilin- and p-75 dependent cleavage of proNGF. The potential ability of local glial cells to provide a targeted supply of NGF may provide an important way to promote trophic (rather than apoptotic) outcomes under conditions where regeneration or sprouting is required.

Regulation of negative affect in schizophrenia: the effectiveness of acceptance versus reappraisal and suppression.

Although general emotion coping difficulties are well documented in schizophrenia, there has been limited study of specific regulatory strategies such as suppression, reappraisal, and acceptance. In the present study, clinical and control participants were asked to watch video clips selected to elicit negative affect while engaging in one of these three different emotion regulation strategies (counterbalanced), versus a passive viewing condition. The experiential and expressive components of emotion were quantified using self-report and facial electromyography, respectively. A major finding was that, in contrast to control participants, individuals with schizophrenia did not report a greater willingness to reexperience negative emotion after engaging in acceptance. These data are discussed in the context of evidence highlighting the potentially important role of acceptance in understanding affective abnormalities in clinical conditions such as schizophrenia.

Poly(ADP-ribose) polymerase inhibition reverses nitrergic neurovascular dysfunctions in penile erectile tissue from streptozotocin-diabetic mice.

INTRODUCTION: Activation of the DNA repair enzyme, poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP), in response to hyperglycemia-driven oxidative/nitrosative stress, may be an important mechanism in the development of vascular and neural complications in diabetes mellitus. However, a role for PARP in diabetic erectile dysfunction (ED) has not been demonstrated. AIM: To assess whether treatment with a novel PARP-1 inhibitor, GPI 15427, could improve neurovascular dysfunction in corpus cavernosum (CC) from diabetic mice. METHODS: Diabetes was induced by streptozotocin in male MF1 mice; duration was 6 weeks. Intervention GPI 15427 treatment (20mg/kg/day intraperitoneal [i.p.]) was given for 2 weeks following 4 weeks of untreated diabetes. CC strips were mounted in aerated organ baths for measurement of pharmacological or electrical stimulation-evoked changes in smooth muscle tension. MAIN OUTCOME MEASURES: Contractile responses to noradrenergic stimulation and to pharmacological agents stimulating endothelium-dependent and -independent relaxation, and nerve-mediated relaxations against a background precontraction. RESULTS: Contractions in response to phenylephrine or activation of noradrenergic nerves were not significantly altered by diabetes. In contrast, maximum nitrergic nerve-mediated relaxation of phenylephrine-precontracted CC was approximately 28% reduced by diabetes: GPI 15427 treatment completely corrected this diabetic deficit. Similarly, maximal nitric oxide (NO)-mediated endothelium-dependent and -independent relaxations to acetylcholine and sodium nitroprusside, against phenylephrine precontraction, were attenuated approximately 37% and 23% by diabetes, respectively. These deficits were completely reversed by PARP-1 inhibition. Furthermore, GPI 15427 corrected a modest diabetic deficit in sensitivity to nitroprusside (EC(50) reduced by 0.14 log units); a similar trend was observed for acetylcholine-induced relaxation. CONCLUSIONS: GPI 15427 treatment provides marked benefits for NO-dependent neurovascular function in diabetic mouse CC. Therefore, PARP-1 inhibition may be worthy of further investigation for diabetes-associated ED.

Impaired cavernous reinnervation after penile nerve injury in rats with features of the metabolic syndrome.

INTRODUCTION: The metabolic syndrome is a cluster of cardiovascular risk factors that predispose toward the development of diseases such as diabetes. Erectile dysfunction (ED) is common in men with metabolic syndrome, but its etiology is poorly understood. Pro-erectile nitrergic nerves innervating penile erectile tissue are also susceptible to mechanical injury during pelvic surgical procedures, which can lead to sexual dysfunction. AIMS: The aims of this article are: (i) to examine erectile function in an experimental model of metabolic syndrome, the phosphoenolpyruvate carboxykinase (PEPCK)-overexpressing rat; and (ii) to study function and cavernous reinnervation after penile nerve crush injury, which permits regeneration, in transgenic rats. METHODS: We analyzed the density of noradrenergic and nitrergic nerves and performed organ bath pharmacology to assess neurogenic activity. MAIN OUTCOME MEASURES: By analyzing changes in neural structure, function, and pharmacologic responses of cavernous tissue after nerve crush injury, we were able to reveal neurologic deficits in rats with metabolic syndrome. RESULTS: Animals with features of metabolic syndrome did not develop notable changes in cavernous autonomic nerve density or nerve-evoked smooth muscle activity. However, regeneration of nitrergic nerves after crush injury in transgenic rats was impaired compared with injured controls. This was manifested as a deficit in axon regrowth and responses to axon activation. However, unlike injured controls, injured PEPCK-overexpressing rats did not develop a reduced maximal response to the nitric oxide (NO) donor, sodium nitroprusside. This suggests preserved NO responsiveness in tissues from rats with metabolic syndrome, despite impaired regeneration and return of function. CONCLUSIONS: This study revealed that rats with features of metabolic syndrome display impaired cavernous nerve regeneration after penile nerve injury, but the degree of functional impairment may be attenuated due to reduced plasticity of NO signaling. This reinnervation deficit may be of clinical relevance for understanding why ED persists in some (particularly aged) men after pelvic surgery.