Basal Nerve Research Articles

Specific Afferent Renal Denervation Prevents Reduction in Neuronal Nitric Oxide Synthase Within the Paraventricular Nucleus in Rats With Chronic Heart Failure.

Renal denervation (RDN) has been shown to restore endogenous neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) and reduce sympathetic drive during chronic heart failure (CHF). The purpose of the present study was to assess the contribution of afferent renal nerves to the nNOS-mediated sympathetic outflow within the PVN in rats with CHF. CHF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, selective afferent RDN (A-RDN) was performed by bilateral perivascular application of capsaicin on the renal arteries. Seven days after intervention, nNOS protein expression, nNOS immunostaining signaling, and diaphorase-positive stained cells were significantly decreased in the PVN of CHF rats, changes that were reversed by A-RDN. A-RDN reduced basal lumbar sympathetic nerve activity in rats with CHF (8.5%±0.5% versus 17.0%±1.2% of max). Microinjection of nNOS inhibitor L-NMMA (L-NG-monomethyl arginine citrate) into the PVN produced a blunted increase in lumbar sympathetic nerve activity in rats with CHF. This response was significantly improved after A-RDN (Δ lumbar sympathetic nerve activity: 25.7%±2.4% versus 11.2%±0.9%). Resting afferent renal nerves activity was substantially increased in CHF compared with sham rats (56.3%±2.4% versus 33.0%±4.7%). These results suggest that intact afferent renal nerves contribute to the reduction of nNOS in the PVN. A-RDN restores nNOS and thus attenuates the sympathoexcitation. Also, resting afferent renal nerves activity is elevated in CHF rats, which may highlight a crucial neural mechanism arising from the kidney in the maintenance of enhanced sympathetic drive in CHF.

Unilateral corneal nerve cutting induces bilateral dry eye disease in a murine model.

Abstract Purpose To investigate the effect of the severing of corneal basal nerve plexus in one eye on bilateral dry eye disease in a murine model. Methods 6 week-old female BALB/c mice were divided into control (n=30) and nerve-cutting (NC) groups (n=30). The left cornea was partially incised with a 2.0mm circular trephine, through the upper two-thirds of the cornea stromal layer. Lissamine green corneal staining and tear volume measurements were performed every week for 4 weeks. At 2 and 4 weeks, dendritic cells, CD4+/CD8+ T cells, regulatory T cells in cervical lymph nodes, conjunctivocornea and spleens were analyzed by flow cytometry. With real-time RT-PCR, neuropeptides were also analyzed in intra-orbital lacrimal glands at 2 weeks. Results In bilateral eyes of mice in NC group, corneal staining grades were increased and tear volumes were decreased. CD11c+CD86hi, CD11c+MHCIIhi cells in conjunctivocornea were increased in trephined eyes at 2 weeks and in contralateral eyes at 4 weeks. CD69 were highly expressed in CD4+/CD8+ T cells in conjunctivocornea of trephined eyes at 4 weeks. CD8+IFNγ+ T cells were increased in contralateral cervical lymph nodes in NC group. Meanwhile, regulatory T cells in spleens were significantly suppressed in NC group. In addition, neuropeptide Y and neutrin were increased in intra-orbital lacrimal glands in NC group Conclusions It suggests that unilateral corneal nerve cutting may induce bilateral dry eye disease by entering activated dendritic cells into the bilateral eyes with a disturbance of immune privilege.

Spatial orientation of the adult cochlea: rotation, tilt, and angle theta 3.

Quantitative description in adult crania of (1) angular orientation of the basal turn of the cochlea relative to the sagittal (termed "rotation") and Frankfort horizontal (termed "tilt") planes, and angle theta 3 [angular relationship of the line defined by the cochlea's spiral center and cochlear (round) window, to the cochlear window]; (2) orientation of the cochlea relative to the plane defined by the horizontal and vertical portions of the facial nerve; (3) orientation of the basal turn of the cochlea relative to the plane of the posterior semicircular canal; and (4) the association of these orientations with the extent of mastoid pneumatization. Postmortem material analysis. From 41 bequeathed anatomical ear-normal cadaveric cranial, high-resolution CT scans were performed of the five crania with the largest and the five with the smallest mastoids. Eleven points in three-dimensional Cartesian space were appointed and studied with the software program FIJI. The median angle values (and ranges) for right ears were: "rotation" 52° (range 47-61); and, "tilt" 84° (79-89). The planes of the cochlear basal turn and facial nerve approximated superimposition: median 15° (2-19). Angle theta 3 for right ears was median 40° (28-44). Bilateral symmetry was found for the relationships between the planes. However, no association of any planar relationship with mastoid pneumatization was suggested. Considering the range of angles found in clinically normal adult specimens, spatial orientation of the cochlea may explain some of the difficulties in implantation.

Specific Afferent Renal Denervation Improves Reduced nNOS in the Paraventricular Nucleus in Rats with Heart Failure

Renal denervation (RDN) has been shown to restore endogenous neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN), and at the same time reduce sympathetic drive during heart failure (HF), however the role of afferent versus efferent renal nerves in this response remains to be determined. The purpose of the present study was to assess the contribution of afferent renal nerves (ARN) in the nNOS within the PVN mediated sympathetic outflow in rats with HF. HF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, selective afferent RDN (A‐RDN) was performed by bilateral perivascular application of capsaicin on the renal arteries. Seven days after intervention, A‐RDN was verified by lack of calcitonin gene‐related peptide in renal pelvic wall. A‐RDN reduced basal lumbar sympathetic nerve activity (LSNA) in rats with HF (8.5 ± 0.5 vs 17.0 ± 1.2 % of Max). nNOS‐positive cells immunostaining and ‐diaphorase staining were significantly decreased in the PVN of HF rats, findings that were ameliorated by A‐RDN. Microinjection of nNOS inhibitor L‐NMMA into the PVN resulted in a blunted increase in LSNA in HF, this response was improved after A‐RDN (ΔLSNA: 25.7 ± 2.4 vs 11.2 ± 0.9%). Resting ARN activity, expressed as a percent of peak ARN activity, was substantially increased in HF compared to sham rats (60.9 ± 2.2 vs 27.7 ± 4.4 %Amax). These results suggest that intact ARN contribute to the reduction of nNOS in the PVN, resulting in activation of the neurons in the PVN of rats with HF. Specific A‐RDN restores nNOS and thus attenuates the sympathoexcitation. Also, resting ARN activity is elevated in HF rats, which may highlight a crucial neural mechanism initiated from the kidney in the maintenance of enhanced sympathetic drive in HF.Support or Funding InformationThis work was supported by NIH grant P01 HL62222.

The potential use of low-frequency tones to locate regions of outer hair cell loss

Current methods used to diagnose cochlear hearing loss are limited in their ability to determine the location and extent of anatomical damage to various cochlear structures. In previous experiments, we have used the electrical potential recorded at the round window –the cochlear response (CR) –to predict the location of damage to outer hair cells in the gerbil. In a follow-up experiment, we applied 10 mM ouabain to the round window niche to reduce neural activity in order to quantify the neural contribution to the CR. We concluded that a significant proportion of the CR to a 762 Hz tone originated from phase-locking activity of basal auditory nerve fibers, which could have contaminated our conclusions regarding outer hair cell health. However, at such high concentrations, ouabain may have also affected the responses from outer hair cells, exaggerating the effect we attributed to the auditory nerve. In this study, we lowered the concentration of ouabain to 1 mM and determined the physiologic effects on outer hair cells using distortion-product otoacoustic emissions. As well as quantifying the effects of 1 mM ouabain on the auditory nerve and outer hair cells, we attempted to reduce the neural contribution to the CR by using near-infrasonic stimulus frequencies of 45 and 85 Hz, and hypothesized that these low-frequency stimuli would generate a cumulative amplitude function (CAF) that could reflect damage to hair cells in the apex more accurately than the 762 stimuli. One hour after application of 1 mM ouabain, CR amplitudes significantly increased, but remained unchanged in the presence of high-pass filtered noise conditions, suggesting that basal auditory nerve fibers have a limited contribution to the CR at such low frequencies.

Commentary: Oxygen regulation of breathing through an olfactory receptor activated by lactate.

Commentary: Oxygen regulation of breathing through an olfactory receptor activated by lactate.

Ontogeny and innervation of taste buds in mouse palatal gustatory epithelium

We investigated the relationship between mouse taste bud development and innervation of the soft palate. We employed scanning electron microscopy and immunohistochemistry using antibodies against protein gene product 9.5 and peripherin to detect sensory nerves, and cytokeratin 8 and α-gustducin to stain palatal taste buds. At E14, nerve fibers were observed along the medial border of the palatal shelves that tracked toward the epithelium. At E15.5, primordial stages of taste buds in the basal lamina of the soft palate first appeared. At E16, the taste buds became large spherical masses of columnar cells scattered in the soft palate basal lamina. At E17, the morphology and also the location of taste buds changed. At E18–19, some taste buds acquired a more elongated shape with a short neck, extending a variable distance from the soft palate basal lamina toward the surface epithelium. At E18, mature taste buds with taste pores and perigemmal nerve fibers were observed on the surface epithelium of the soft palate. The expression of α-gustducin was demonstrated at postnatal day 1 and the number of pored taste buds increased with age and they became pear-shaped at 8 weeks. The percent of pored fungiform-like papillae at birth was 58.3% of the whole palate; this increased to 83.8% at postnatal day 8 and reached a maximum of 95.7% at 12 weeks. The innervation of the soft palate was classified into three types of plexuses in relation to taste buds: basal nerve plexus, intragemmal and perigemmal nerve fibers. This study reveals that the nerve fibers preceded the development of taste buds in the palate of mice, and therefore the nerve fibers have roles in the initial induction of taste buds in the soft palate.

In vivo confocal microscopic characterisation of the cornea in chronic graft-versus-host disease related severe dry eye disease

AimsTo first describe in vivo confocal microscopic (IVCM) corneal findings in severe dry eye syndrome due to ocular chronic graft versus host disease (cGvHD) after allogeneic stem cell transplantation.MethodsIVCM of...

Microanatomy and ultrastructure of outer mantle epidermis of the cuttlefish, Sepia esculenta (Cephalopoda: Sepiidae)

This study describes the ultrastructural characteristics of external epidermis of mantle of Sepia esculenta using light and electron microscopy. The epidermis was thicker on the ventral surface than on the dorsal surface, with a higher secretory cell distribution on the ventral surface than on the dorsal surface. The epidermis was a single layer composed of epithelial cells, secretory cells, ciliated cells and neuroglial cells. Epithelial cells were columnar with well-developed microvilli on the free surface, and the microvilli were covered with glycocalyx. The epithelial cells were connected to the neighboring cells by tight junctions and membrane interdigitations of the apico-frontal surface. Well-developed microfilaments were arranged in a vertical direction in the cortical cytoplasm. The secretory cells were categorized into three types (A, B and C) in accordance with the light microscopical characteristics and ultrastructures of the secretory granules. The distribution of these cells was in the following order: Type A>Type B>Type C. SEM observation revealed that the secretory pore size of the Type A secretory cells was approximately 8.6μm×12.2μm. Cytoplasm displayed a red color as the result of Masson's trichrome stain and H–E stain, and contained polygonal granules of approximately 1.2μm2 with a high electron density. The secretory pore size of the Type B secretory cells was approximately 10.1μm×12.1μm. As the results of AB–PAS (pH 2.5) and AF–AB (pH 2.5) reactions, the cytoplasm displayed a red color. The cells contained membrane bounded secretory granules with very low electron density. The secretory pore of the Type C secretory cells was circular shape, and approximately 5.5μm×5.5μm. Cytoplasm was found to be homogeneous under H–E stain and Masson's trichrome stain, and displayed a red color. As the result of AB–PAS (pH 2.5) reaction, the cytoplasm displayed a red color. The electron density of the secretory substance was the highest among the three types of secretory cells. The ciliated cells had a ciliary tuft on the free surface and were distributed throughout the mantle with the exception of the adhesive organs. Neuroglial cells were connected to the basal membrane, epithelial cells, secretory cells and nerve fibers through cytoplasmic process, and contained neurosecretory granules with high electron density within the cytoplasm.

Morphometric features of corneal epithelial basal cells, and their relationship with corneal nerve pathology and clinical factors in patients with type2 diabetes.

We compared the morphometric features of corneal epithelial basal cells between patients with type2 diabetes mellitus and healthy controls, and analyzed the relationship of these features with corneal nerve fiber pathology and clinical factors in the patients. Corneal epithelial basal cells and corneal nerve fibers were visualized by corneal confocal microscopy in 75 patients with type2 diabetes and 42 age-matched controls. Density, area and area variability of corneal epithelial basal cells, as well as the width of the intercellular space between neighboring cells, were evaluated for both groups. Patients showed decreased density (P<0.02) and area (P<0.0001), larger area variability (P<0.0001) and a wider intercellular space (P<0.0001) compared with controls. Density correlated inversely with area (P<0.0001), width of intercellular space (P<0.03) and beading frequency (P<0.03), whereas it correlated directly with prothrombin time (P<0.002) and activated partial thromboplastin time (P<0.03). Area correlated inversely with duration of diabetes (P<0.05) and coefficient of variation of area (P<0.01), whereas it correlated directly with beading frequency (P<0.05). Area variability correlated inversely with area (P<0.01) and prothrombin time (P<0.01), whereas it correlated directly with fibrinogen level (P<0.0001). Type2 diabetes induces morphometric changes in corneal epithelial basal cells; this seems to be related to the morbid period of diabetes, beading frequency of corneal nerve fibers and blood coagulation state.

Congenital Myasthenic Syndrome Due to Choline Acetyltransferase Mutations in Infants

Congenital myasthenic syndromes are inherited disorders caused by various defects in neuromuscular transmission. Although the typical presentation is fatigable weakness with prominent cranial involvement, neonates can lack these hallmark manifestations, and in those with choline acetyltransferase gene mutations, basal electrophysiological testing can yield negative findings. The authors report the case of a male infant presenting at birth with oculomotor and bulbofacial weakness, hypotonia, clubfoot, and severe respiratory insufficiency. Electromyography showed myogenic signs, and basal repetitive nerve stimulation yielded negative findings. Since age 6 months, the infant had progressively improved, acquiring autonomous respiration. Prolonged subtetanic repetitive nerve stimulation disclosed a marked decremental response compatible with suspected congenital myasthenic syndrome with episodic apnea. Genetic testing identified 2 novel choline acetyltransferase mutations (R470X, F580C). Keeping a high clinical suspicion of this rare condition and undertaking early comprehensive electrophysiological assessments including prolonged repetitive nerve stimulation (10 Hz for 5 minutes) can expedite the diagnosis.

Mechanisms of Blunted Muscle Vasodilation During Peripheral Chemoreceptor Stimulation in Heart Failure Patients

We described recently that systemic hypoxia provokes vasoconstriction in heart failure (HF) patients. We hypothesized that either the exaggerated muscle sympathetic nerve activity and/or endothelial dysfunction mediate the blunted vasodilatation during hypoxia in HF patients. Twenty-seven HF patients and 23 age-matched controls were studied. Muscle sympathetic nerve activity was assessed by microneurography and forearm blood flow (FBF) by venous occlusion plethysmography. Peripheral chemoreflex control was evaluated through the inhaling of a hypoxic gas mixture (10% O(2) and 90% N(2)). Basal muscle sympathetic nerve activity was greater and basal FBF was lower in HF patients versus controls. During hypoxia, muscle sympathetic nerve activity responses were greater in HF patients, and forearm vasodilatation in HF was blunted versus controls. Phentolamine increased FBF responses in both groups, but the increase was lower in HF patients. Phentolamine and N(G)-monomethyl-l-arginine infusion did not change FBF responses in HF but markedly blunted the vasodilatation in controls. FBF responses to hypoxia in the presence of vitamin C were unchanged and remained lower in HF patients versus controls. In conclusion, muscle vasoconstriction in response to hypoxia in HF patients is attributed to exaggerated reflex sympathetic nerve activation and blunted endothelial function (NO activity). We were unable to identify a role for oxidative stress in these studies.

Quantification of burst‐to‐burst variability of basal phrenic nerve discharge in adult in vivo rat

The respiratory control system is highly dynamic; however, typical measures of respiratory variability are often limited to computing the mean±SE and/or the coefficient of variation (CV), which do not distinguish between short‐term and long‐term variability. To overcome this limitation, some studies have employed Poincaré plot (PP), irregularity score (IS), or approximate entropy (ApEn) analyses; however, these analysis methods have not been implemented and compared on a single data set. To address this issue, we used all of the above analysis methods to quantify burst‐to‐burst variability of basal phrenic nerve discharge (n=300 bursts) recorded from anesthetized or decerebrate adult rat. We found that while all methods provide insight into the overall burst‐to‐burst variability, PP, IS, and ApEn analyses provide novel information about the patterning of the data spread. Moreover, these methods provide novel information about the short‐term vs long‐term variability. We suggest that these additional analysis methods be used to more fully capture patterns of long‐term variability and provide complementary insight into the dynamics underlying the respiratory control system. Supported by HL63175

Influence of different classes of anesthetics on burst‐to‐burst variability of basal phrenic nerve discharge in adult in vivo rat

The respiratory control system is highly dynamic, allowing for breath‐to‐breath adjustments to both physiological and pathological conditions. Ongoing work in our laboratory in the adult in vivo rat focuses on exploring the influence of different classes of anesthetics on various respiratory behaviors, including basal respiratory burst patterns. In the current study, we expand on this work by examining the influence of different classes of anesthetics on burst‐to‐burst variability of basal phrenic nerve discharge. Poincaré plot and coefficient of variation analyses were performed on 300 consecutive phrenic bursts obtained from urethane (U), inactin used alone (IN) or in combination with ketamine (IN‐K) or xylazine (IN‐X), sodium pentobarbital (P), ketamine in combination with xylazine (K‐X), propofol (PRO), and isoflurane (ISO) anesthetized rats; decerebrate rats were also studied. Our analyses suggest that different classes of anesthetics differentially influence the short‐term and long‐term variability of phrenic burst frequency and timing, and that typically used measures of variability may not fully capture long‐term patterns of variability. Supported by HL63175

Therapeutic effects of human amniotic epithelial cell transplantation on double-transgenic mice co-expressing APPswe and PS1ΔE9-deleted genes

Human amniotic epithelial cells (HAECs), which exhibit characteristics of embryonic and pluripotent stem cells, could be utilized for cell therapy without legal or ethical problems. Double-transgenic (TG) mice (n=20) and wild-type (WT) mice (n=20) were randomly assigned to two groups, respectively. The transplantation group was treated with HAECs and the control group with PBS. A six-radial arm water maze was used to assess spatial memory. Immunofluorescence was utilized to track HAEC survival. Immunohistochemistry was used to determine octamer-binding protein 4 (oct-4) and nanog expression in the HAECs. High-performance liquid chromatography (HPLC) was used to measure acetylcholine levels in the hippocampus. The density of cholinergic neurons in the basal forebrain and nerve fibers in the hippocampus was measured following acetylcholinesterase staining. Results showed that transplanted HAECs survived for at least eight weeks and migrated to the third ventricle without immune rejection. Graft HAECs also expressed the specific stem cell markers oct-4 and nanog. Compared with the control group, HAEC transplantation significantly ameliorated spatial memory deficits in TG mice, as well as increased acetylcholine levels and the number of hippocampal cholinergic neurites. Intracerebroventricular HAEC transplantation improved spatial memory in double-TG mice, and results suggested that increased acetylcholine levels in the hippocampus, released by surviving cholinergic neurites, were responsible for this improvement.

Nerve Terminal Growth Remodels Neuromuscular Synapses in Mice following Regeneration of the Postsynaptic Muscle Fiber

Muscle fibers degenerate and regenerate in response to contractile damage, during aging, and in various muscle diseases that weaken the fibers. It is known that degeneration and regeneration of the segment of the postsynaptic fiber produces dramatic alterations in the neuromuscular junction (NMJ) that forms on the regenerated fiber, but the mechanisms here are incompletely understood. We have used a laser microbeam to damage the postsynaptic fibers at individual NMJs in the sternomastoid muscle of living young adult mice and then followed the synapses vitally over time using fluorescent proteins expressed in motor neurons and glial cells and staining of postsynaptic acetylcholine receptors. We find, in contrast to previous reports, that the mouse nerve terminal retains contact with the synaptic basal lamina marked by cholinesterase staining even in the absence of the target, showing that this terminal does not require a continuous supply of target-derived molecules for its maintenance. Thus, remodeling of the nerve terminal during the period of target absence does not explain the subsequent changes in the new NMJ. Rather, we see that the synapse becomes altered as the new fiber segment regenerates. Mechanisms for remodeling the synapse include failure of the regenerating muscle fiber to contact the old basal lamina and nerve terminal, growth of the nerve terminal and its glia toward the regenerating fiber, and remodeling of the initial contact as the nerve terminal becomes varicose.

Comparison of pelvic plexus blockade to other conventional techniques of analgesia in transrectal ultrasound guided prostate biopsy

To compare the degree of pain, efficacy and safety of pelvic plexus block to other conventional techniques of analgesia in 12 core transrectal ultrasound guided biopsy of prostate. The study included 160 consecutive cases of prostate biopsy, prospectively randomized into four groups of 40 each -Men in group 1 (control arm) received lignocaine gel (2%) only; Group 2 received lignocaine gel with basal periprostatic nerve block (BPNB) with 2% lignocaine; Group 3 received lignocaine gel (2%) with apical periprostatic block (APNB) with 2% lignocaine and Group 4 received lignocaine gel with pelvic plexus block. Pain was recorded on a 10 point visual analogue scale by a nurse. Patients in pelvic plexus block group had lowest pain score (1.25±0.43) while lignocaine injection than BPNB (1.53±0.45) and APNB (1.58±0.50, P value = 0.008). The mean pain score among 4 groups while taking the biopsy cores were 4.85, 2.67, 2.48 and 1.95, respectively. Patients who received pelvic plexus block experienced least pain than BPNB and APNB groups (p value 0.001 and 0.002, respectively). Perineal pain persisted longer in pelvic plexus block group than apical and periprostatic groups. Duration of dysuria was less in pelvic plexus nerve block group. Hematuria and rectal bleed complications were comparable in all groups. Prostate biopsy should be performed with either periprostatic nerve block (basal or apical) or pelvic plexus block under Doppler ultrasonography guidance. Pelvic plexus block provides superior analgesia to basal and apical periprostatic block.

Laser Scanning In Vivo Confocal Microscopy Demonstrating Significant Alteration of Human Corneal Nerves Following Herpes Zoster Ophthalmicus

60-YEAR-OLD WOMAN with herpes zoster ophthalmicus(HZO) of the right eye was treated with 800 mg ofacyclovir5timesperdayfor7days. Therewasnosignificantmedicalhis- tory. She developed reduced vision and ocular pain due to HZO disci- form keratouveitis (a central disc- like region of corneal edema with objective of the microscope was placedincontactwiththecorneaand thepatientwasaskedtofixateondis- tance targets arranged in a grid pat- tern to enable acquisition of mul- tipleconfocalimagesoverawidearea of cornea. Macromedia Freehand 10 (SanFrancisco,California)wasused to arrange images into wide-field montages of the subbasal nerve plexus. A montage of the left sub- basal nerve plexus demonstrated nerve fiber bundles arranged in a ra- diatingpattern,convergingtoforma typical clockwise whorl, or vortex, pattern,andLangerhans(antigenpre- senting) cells were distributed throughout the imaged region (Figure 1). In contrast, a montage of the right subbasal nerve plexus could not be produced owing to the scarcity of subbasal nerves. Indeed, only occasional nonbranching sub- basal nerves were visible in the mid- peripheral cornea (Figure 2A) and most images of the right cornea con- sisted of a bare, nerve-free Bowman layer (Figure 2B) with Langerhans cells (Figure 2C). COMMENT

Blood Pressure Regulation in Humans

Within an individual, diastolic blood pressure (DBP) is negatively related to sympathetic burst incidence, such that lower pressure is associated with high burst incidence. Our goal was to explore the use of a calculation of a DBP "error signal" in the control of muscle sympathetic nerve activity in men and women. Baseline muscle sympathetic nerve activity was measured in healthy young men (n=22) and women (n=28). Women had significantly lower muscle sympathetic nerve activity than men (29+/-3 versus 43+/-2 bursts per 100 heartbeats; P<0.05). For each individual, the DBP at which there is a 50% likelihood of a muscle sympathetic nerve activity burst, the "T50" value, was calculated. Mean DBP was subtracted from the T50 blood pressure as an approximate error signal for burst activation. Error signal was negative in both sexes, indicating that DBP in both sexes was higher than the DBP value associated with a 50% burst likelihood. However, average error signal was significantly larger in women (-4+/-2 mm Hg) than in men (-1+/-0 mm Hg; P<0.05 versus women). We conclude that women operate at a mean DBP greater than their T50 compared with men, and this may be a contributing factor to low basal muscle sympathetic nerve activity in women. The relationship between error signal and burst incidence may provide important insight into the control of muscle sympathetic nerve activity across sexes and in various populations.

Neonatal stress affects vulnerability of cholinergic neurons and cognition in the rat: Involvement of the HPA axis

Adverse experiences early in life may sensitize specific neurocircuits to subsequent stressors. We have evaluated in maternal separation (MS) rats, an animal paradigm of early-life stress, the effects of a selective cholinergic lesion on cognitive function as well as susceptibility of cholinergic neurons to the lesion. MS rats subjected to a cholinergic lesion by administration of the immunotoxin 192 IgG-saporin, showed significant decreases in both choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity compared to control lesioned rats. Morris water maze results revealed a significant impairment in learning and memory function in MS adult rats and further cognitive deficits after the lesion. The lesion of cholinergic neurons induced a significant decrease in glucocorticoid receptor density in MS rats, accompanied by increases in CRF mRNA expression. Decreases in NGF and increases in NGF-p75NTR expression have also been found in MS rats. Our results suggest that vulnerability of basal forebrain cholinergic nerve cells might be affected by the HPA axis. The present data are discussed not only in terms of conditions that occur during ageing or Alzheimer disease, but also regarding a purported involvement of the cholinergic system in the regulation of HPA axis activity.