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Effects of chronic dietary restriction on sensory-motor function and susceptibility to stressor stimuli in the laboratory rat.

Two sets of experiments describing the effects of chronic undernutrition on sensory-motor function and susceptibility to environmental stressors are described. In the first, Fischer 344 rats between 10 and 12 months of age were placed on an every-other-day feeding regimen. Behavioral tests designed to assess sensory function (auditory and visual thresholds), somato-motor competence (hang time from a horizontal wire, balance on a narrow beam, descent of a wire mesh pole), and sensory-motor integrity (auditory startle) were then conducted every 3 to 6 months. Chronic undernutrition significantly increased life span and increased somato-motor competence but did not affect sensory function or sensory-motor integrity. In the second set of experiments both acute and chronic dietary restriction impaired the ability of young adult Sprague-Dawley rats to effectively thermoregulate in response to a cold environment. Body temperature dropped more rapidly and recovered at a slower rate in the dietarily restricted animals. Fischer 344 rats maintained on a restricted diet for 16 months were similarly impaired. The latter findings suggest that techniques for extending life span based on laboratory animal models may have little relevance to either animals or humans living in their natural habitats where a wide variety of environmental stressors are encountered.

Animals↗

Behavioral evidence in rats for a peptidergic-noradrenergic interaction in cutaneous sensory and vascular function.

Cutaneous sensory and vascular function was examined following application of capsaicin to the sciatic nerve and systemic injection of guanethidine. Together the two drugs produced a reduction in sensitivity to heat-pain, inflammatory pain (formalin test), tactile stimulation and skin temperature of the foot that exceeded the effects of either drug alone. The inflammation produced by an injection of formalin to the plantar surface of the hind paw was reduced equally by capsaicin or capsaicin + guanethidine. Cold sensitivity and inflammation produced by yeast injection were unaffected by all treatments. The data imply a peripheral interaction between peptidergic and noradrenergic systems with significant functional implications that may be important in the pathology of familial dysautonomia.

Animals↗

New autonomic and sensory neuropathy with loss of adrenergic sympathetic function and sensory neuropeptides.

A 30-year-old woman with longstanding dizziness was found to have a severe postural fall in blood pressure and a reduced skin axon-reflex flare response. Autonomic tests indicated selective impairment of adrenergic sympathetic function. Plasma noradrenaline, adrenaline, dopamine, and dopamine beta hydroxylase were undetectable. Skin biopsy specimens showed loss of tyrosine hydroxylase and neuropeptide Y (markers of adrenergic sympathetic fibres) and of substance P and calcitonin gene-related peptide (sensory neuropeptides). A sural nerve biopsy specimen showed severe depletion of unmyelinated fibres. The constellation of losses were compatible with nerve growth factor (NGF) deprivation, which was confirmed on assay. This new syndrome may be explained by loss of trophic action of NGF.

Adrenergic Fibers↗

Autonomic and sensory nerve function in diabetic foot ulceration.

Peripheral sensory and autonomic nerve dysfunction are thought to be crucial factors in the pathogenesis of diabetic foot ulceration. However, their relative importance is not known. In this study we have compared peripheral sensory nerve function and cardiac autonomic reflexes in 51 diabetics with a history of foot ulceration and 480 diabetic control subjects. In the diabetics with ulceration ankle reflexes were absent or impaired and vibration perception threshold reduced in 96.1% and 82.4%, respectively, compared with 40.8% and 25.8%, respectively, in control subjects (P less than 0.001). Cardiac autonomic tests were abnormal more frequently in the diabetics with ulceration and an autonomic score derived from four tests was abnormal in 62.8% of those with ulceration compared with 13.5% of those without ulceration (P less than 0.001). Discriminant analysis of the two groups of diabetes showed that an abnormal autonomic score was the best predictor of foot ulceration in diabetic patients.

Diabetic Neuropathies↗

Function of sensory input in insect motor systems.

The organization and function of sensory input has been examined in three insect motor systems: locust jumping, cockroach walking, and locust flight. In these three systems sensory input is primarily involved in the production of the normal patterns of motor activity rather than in the compensation for sudden changes in the external environment. At least two general functions for sensory input in the normal patterning of motor activity can be identified: (1) compensation for changes in the peripheral elements of the motor system which occur as a result of use and maturation and (2) regulation of switching from one phase of a movement to another following the attainment of a specific state by peripheral structures. Reflex pathways may exist for compensating for sudden environmental disturbances but these have not yet been clearly demonstrated.

Animals↗

Nicotinic acetylcholine receptors in sensory cortex.

Acetylcholine release in sensory neocortex contributes to higher-order sensory function, in part by activating nicotinic acetylcholine receptors (nAChRs). Molecular studies have revealed a bewildering array of nAChR subtypes and cellular actions; however, there is some consensus emerging about the major nAChR subtypes and their functions in sensory cortex. This review first describes the systems-level effects of activating nAChRs in visual, somatosensory, and auditory cortex, and then describes, as far as possible, the underlying cellular and synaptic mechanisms. A related goal is to examine if sensory cortex can be considered a model system for cortex in general, because the use of sensory stimuli to activate neural circuits physiologically is helpful for understanding mechanisms of systems-level function and plasticity. A final goal is to highlight the emerging role of nAChRs in developing sensory cortex, and the adverse impact of early nicotine exposure on subsequent sensory-cognitive function.

Animals↗

Experimentally induced ulcers and gastric sensory-motor function in rats.

Prior studies have demonstrated that inflammation can sensitize visceral afferent neurons, contributing to the development of hyperalgesia. We hypothesized that both afferent and efferent pathways are affected, resulting in changes in motor and sensory function. Kissing ulcers (KU) were induced in the distal stomach by injecting 60% acetic acid for 45 s into a clamped area of the stomach. In controls, saline was injected into the stomach. A balloon catheter was surgically placed into the stomach, and electromyographic responses to gastric distension were recorded from the acromiotrapezius muscle at various times after ulcer induction. The accommodation reflex was assessed by slowly infusing saline into the distally occluded stomach. Gastric pressure changes in response to vagal stimulation were measured in anesthetized rats. Contractile function of circular muscle strips was examined in vitro using force-displacement transducers. KU caused gastric hypersensitivity that persisted for at least 14 days. Fluid distension of the stomach led to a rapid pressure increase in KU but not in control animals, consistent with an impaired accommodation reflex. Gastric ulcers enhanced the contractile response to vagal stimulation, whereas the effect of cholinergic stimulation on smooth muscle in vitro was not changed. These data suggest that inflammation directly alters gastric sensory and motor function. Increased activation of afferents will trigger vagovagal reflexes, thereby further changing motility and indirectly activating sensory neurons. Thus afferent and efferent pathways both contribute to the development of dyspeptic symptoms.

Acetic Acid↗

Anatomy and histology of joint innervation.

Joint diseases are mostly accompanied with hyperalgesia and/or pain in the joint region. As about 60% of the knee joint innervation may be classified as nociceptive, the structure of joint afferents became a matter of interest. The function of a sensory nerve fibre may be defined by its location, its morphology and its biochemical composition. This review is therefore focused on the composition of articular nerves, the morphology of sensory endings, their content of mitochondria and neuropeptides, and the plasticity of neuropeptide synthesis during joint inflammation. As the knee joint of the cat belongs to the best examined articular tissue concerning the sensory function of its afferent innervation, most of the morphological data have also been determined in this model. The histological studies revealed a dense afferent innervation of all parts of joints. Most of the afferents terminate in non-corpuscular endings. Although the ultrastructure of these endings has been examined in great detail, up to now no morphological and biochemical details can be used to discriminate between mechanosensitive and nociceptive afferents. Only the differences in the content of mitochondria in single nerve fibres may be related to different sensory functions. The content of different neuropeptides in joint afferents highlights an additional efferent function of a proportion of joint afferents. The dense innervation with peptidergic joint afferents indicates an important, but up to now mainly unknown role of neuropeptides in a normal joint. Pathological conditions like joint inflammations lead to an enhanced release of neuropeptides into the joint tissue and a specific upregulation of neuropeptide biosynthesis in articular afferents.

Cartilage, Articular↗

Marshall Parks lecture. Binocular sensory outcomes in accommodative ET.

PURPOSE: To review what is known about the normal maturational sequence for fusion and stereopsis and the binocular sensory deficits associated with accommodative esotropia (ET) and to explore the clues that accommodative ET provides about critical periods for binocular sensory function. METHODS: Studies of binocular sensory function during infancy and early childhood are presented. RESULTS: Most of the maturation of binocular sensory function occurs during the first year of life, yet a later abnormal visual experience-such as the onset of accommodative ET--can profoundly and permanently disrupt fusion and stereopsis. CONCLUSIONS: Some binocular sensory deficits may exist before the onset of accommodative ET, but others may result directly from abnormal binocular experience. The functional organization of the maturing visual system appears to be maximally sensitive to disruption by abnormal visual experience during the first months of life, but susceptibility continues until at least 4 years of age.

Accommodation, Ocular↗

[Sensory sphere function in children with enuresis].

The kinesthetic and acoustic analyzers were investigated in 62 enuretic and 50 healthy children. In patients, the sensitivity thresholds of the analyzers were substantially increased. The fall in function of the sensory sphere is a major pathogenetic factor of the disease.

Adolescent↗

Factors in prostate cancer metastasis.

Death related to prostate cancer is invariably due to the tumor metastasis (to lungs, skeleton and lymph nodes). Tumor cell metastatic behaviour is still poorly understood. The R3327 prostate tumor model in the male Copenhagen rat offers an opportunity to investigate the different aspects of metastatic processes in vivo and to evaluate effects of current and new treatment approaches. Lymphatic spread of cancer cells can be measured by determining volume of local load in successive draining lymph node stations. Surgical removal of primary tumor and inguinal lymph node shows that lymphatic metastasis in the R3327-MATLyLu tumor variant is a continuous progressive phenomenon, which starts already in early stages of tumor growth after subcutaneous transplantation. Spread to the lungs can be quantified by enumeration of macroscopically visible pleural lung colonies. Metastatic spread to the lungs can be mimicked by intravenous injection of monodispersed tumor cell suspension. Within 10 days pleural tumor colonies become visible. Effects of different agents and treatments like chemotherapeutic drugs, heparin, surgery and high energy shock wave (HESW) treatment have been described using these methods. Recently, metastasis to the vertebral column was induced by temporal occlusion of venous blood flow through the caval veins while injecting tumor cells in the lateral tail vein. The resulting osteoblastic metastatic lesions in the lumbar vertebrae and the concomitant spinal cord compression led in time to the loss of motoric and sensory function of the hind legs. These observations permit investigation of the mechanisms of bone metastasis based on biological functions, i.e. sensory and motoric function of the hind legs. Finally, it can be said that the various variants of the R3327 rat prostate tumor offer an appropriate model to study various aspects of prostate cancer and metastasis.

Animals↗

Constructs underlying measures of sensory-motor functions.

Many pathognomonic indicators of brain damage are characterized by deficits in sensory and/or motor functions. The strength of these pathognomonic signs has led to reliance on clinical administration and interpretation in the assessment of sensory and motor functions. Subsequently, the majority of measures designed to assess sensory and motor functions lack adequate reliability and psychometric confirmation of their utility. The Dean-Woodcock Sensory-Motor Battery (DWSMB) was designed to standardize the administration and interpretation of sensory-motor functions and has demonstrated satisfactory reliability. The present study further examined the psychometric properties of the DWSMB through factor analysis. It was hypothesized that at least two factors would emerge representing sensory and motor functions, respectively. A third possible factor that would reflect subcortical functioning was also hypothesized. Principal components analysis on data from over 600 participants supported a three-factor solution which accounted for 50.9% of the total variance. However, factor loadings revealed more dual loadings than expected, and factors emerged according to complexity rather than basic sensory, motor, and subcortical factors. Regardless, these data provide empirical evidence for the conceptualization of sensory-motor skills in a manner that incorporates subcortical abilities. These data also provide support for the underlying constructs of the DWSMB.

Journal Article↗

Numb rats walk - a behavioural and fMRI comparison of mild and moderate spinal cord injury.

Assessment of sensory function serves as a sensitive measure for predicting the functional outcome following spinal cord injury in patients. However, little is known about loss and recovery of sensory function in rodent spinal cord injury models as most tests of sensory functions rely on behaviour and thus motor function. We used functional magnetic resonance imaging (fMRI) to investigate cortical and thalamic BOLD-signal changes in response to limb stimulation following mild or moderate thoracic spinal cord weight drop injury in Sprague-Dawley rats. While there was recovery of close to normal hindlimb motor function as determined by open field locomotor testing following both degrees of injury, recovery of hindlimb sensory function as determined by fMRI and hot plate testing was only seen following mild injury and not following moderate injury. Thus, moderate injury can lead to near normal hindlimb motor function in animals with major sensory deficits. Recovered fMRI signals following mild injury had a partly altered cortical distribution engaging also ipsilateral somatosensory cortex and the cingulate gyrus. Importantly, thoracic spinal cord injury also affected sensory representation of the upper nonaffected limbs. Thus, cortical and thalamic activation in response to forelimb stimulation was significantly increased 16 weeks after spinal cord injury compared to control animals. We conclude that both forelimb and hindlimb cortical sensory representation is altered following thoracic spinal cord injury. Furthermore tests of sensory function that are independent of motor behaviour are needed in rodent spinal cord injury research.

Animals↗

Associations of sensory-motor functions with poor mobility in 75- and 80-year-old people.

This study investigated the associations of sensory-motor functions with mobility in elderly people. All 75- and 80-year-old residents of the city of Jyväskylä, Finland, were invited to take part in the study. A total of 617 (93%) persons were interviewed, and 500 (75%) took part in laboratory examinations. Self-reported mobility was recorded during the interview. Basic mobility functions (maximal walking speed and stair-mounting ability) and sensory-motor functions (maximal isometric muscle strength, standing balance, reaction time and visual acuity) were measured in the laboratory. Multivariate analyses showed that poor sensory-motor functions were significantly associated with poor performance in basic mobility functions and that poor performance in basic mobility functions was associated with self-reported disability in mobility. The associations discovered were consistent with models of the disablement process. Muscle strength, balance, reaction time and vision all have individual significance for mobility, underlining the need for multifactorial approaches in prevention and rehabilitation.

Activities of Daily Living↗

Behavioral phenotyping of mice in pharmacological and toxicological research.

The evaluation of behavioral effects is an important component for the in vivo screening of drugs or potentially toxic compounds in mice. Ideally, such screening should be composed of monitoring general health, sensory functions, and motor abilities, right before specific behavioral domains are tested. A rational strategy in the design and procedure of testing as well as an effective composition of different well-established and reproducible behavioral tests can minimize the risk of false positive and false negative results in drug screening. In the present review we describe such basic considerations in planning experiments, selecting strains of mice, and propose groups of behavioral tasks suitable for a reliable detection of differences in specific behavioral domains in mice. Screening of general health and neurophysiologic functions (reflexes, sensory abilities) and motor function (pole test, wire hang test, beam walking, rotarod, accelerod, and footprint) as well as specific hypothesis-guided testing in the behavioral domains of learning and memory (water maze, radial maze, conditioned fear, and avoidance tasks), emotionality (open field, hole board, elevated plus maze, and object exploration), nociception (tail flick, hot plate), psychiatric-like conditions (porsolt swim test, acoustic startle response, and prepulse inhibition), and aggression (isolation-induced aggression, spontaneous aggression, and territorial aggression) are described in further detail. This review is designed to describe a general approach, which increases reliability of behavioral screening. Furthermore, it provides an overview on a selection of specific procedures suitable for but not limited to behavioral screening in pharmacology and toxicology.

Animals↗

Structural basis for sensory rhodopsin function.

The crystal structure of sensory rhodopsin II from Natronobacterium pharaonis was recently solved at 2.1 A resolution from lipidic cubic phase-grown crystals. A critical analysis of previous structure-function studies is possible within the framework of the high-resolution structure of this photoreceptor. Based on the structure, a molecular understanding emerges of the efficiency and selectivity of the photoisomerization reaction, of the interaction of the sensory receptor and its cognate transducer protein HtrII, and of the mechanism of spectral tuning in photoreceptors. The architecture of the retinal binding pocket is compact, representing a major determinant for the selective binding of the chromophore, all-trans retinal to the apoprotein, opsin. Several chromophore-protein interactions revealed by the structure were not predicted by previous mutagenesis and spectroscopic analyses. The structure suggests likely mechanisms by which photoisomerization triggers the activation of sensory rhodopsin II, and highlights the possibility of a unified mechanism of signaling mediated by sensory receptors, including visual rhodopsins. Future investigations using time-resolved crystallography, structural dynamics, and computational studies will provide the basis to unveil the molecular mechanisms of sensory receptors-mediated transmembrane signaling.

Amino Acid Sequence↗

Isolated dysarthria due to extracerebellar lacunar stroke: a central monoparesis of the tongue.

OBJECTIVES: The pathophysiology of dysarthria can preferentially be studied in patients with the rare lacunar stroke syndrome of "isolated dysarthria". METHODS: A single study was carried out on seven consecutive patients with sudden onset of isolated dysarthria due to single ischaemic lesion. The localisation of the lesion was identified using MRI. The corticolingual, cortico-orofacial, and corticospinal tract functions were investigated using transcranial magnetic stimulation. Corticopontocerebellar tract function was assessed using 99mTc hexamethylpropylene amine oxime-single photon emission computerised tomography (HMPAO-SPECT) in six patients. Sensory functions were evaluated clinically and by somatosensory evoked potentials. RESULTS: Brain MRI showed the lesions to be located in the corona radiata (n=4) and the internal capsule (n=2). No morphological lesion was identified in one patient. Corticolingual tract function was impaired in all patients. In four patients with additional cortico-orofacial tract dysfunction, dysarthria did not differ from that in patients with isolated corticolingual tract dysfunction. Corticospinal tract functions were normal in all patients. HMPAO-SPECT showed no cerebellar diaschisis, suggesting unimpaired corticopontocerebellar tract function. Sensory functions were not affected. CONCLUSION: Interruption of the corticolingual pathways to the tongue is crucial in the pathogenesis of isolated dysarthria after extracerebellar lacunar stroke.

Cerebellum↗

Evidence that nerve growth factor promotes the recovery of peripheral neuropathy induced in mice by cisplatin: behavioral, structural and biochemical analysis.

In this study we investigate the neurotoxic action of Cisplatin (6 micrograms/g body weight for 5 treatment cycles during 15 weeks with a total dose of 30 micrograms/g), an antitumor drug, and its effect on the level of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in peripheral tissues. We found that Cisplatin in adult rodents impairs peripheral sensory function and both sympathetic and sensory peripheral innervation as shown by the hot-plate response, catecholamine distribution and substance P immunoreactivity respectively. These changes are associated with decreased NGF in intestine, paws, and bladder while NGF increased in the spinal cord. Also BDNF decreased in bladder and paws and increased in spinal cord and intestine. To further investigate the role of NGF in the pathogenesis of Cisplatin-induced peripheral neuropathies a group of animals was injected with NGF (1 microgram/g every 4 days for 4 times) following Cisplatin treatment and evaluated for sensory function, sympathetic and sensory innervation and BDNF levels. Data demonstrated that exogenous NGF administration is able to restore biochemical, structural and functional changes induced by Cisplatin. These findings suggest that the reduction of NGF availability could be a cause of Cisplatin-induced peripheral neuropathies and that NGF exogenous administration could prevent or reduce Cisplatin neurotoxicity also in cancer patients, reducing the side effects of chemotherapy.

Animals↗