bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Decentralization on Cholinergic Neurotransmission in Neurons of Mouse Major Pelvic Ganglia
Authors: Kyi Cindy , Garcia Virginia , Schulz David J 
Published: November 2023

Major pelvic ganglia (MPG) of mouse contains postganglionic neurons innervating urinary bladder, the genitals and distal colon. Pelvic ganglia receive cholinergic parasympathetic inputs from the preganglionic neurons in the sacral cord through pelvic nerve, and sympathetic inputs from those in the lumbosacral cord through hypogastric nerve. The axons from the pelvic ganglion synapse onto postganglionic neurons on the target organ, releasing acetylcholine from parasympathetic axons and noradrenaline from sympathetic axons.Damage to the pelvic nerve due to complications from surgeries carried out in the pelvic area often results in micturition and erectile dysfunctions. The goal of this project is to understand the impact of loss of neural input on nicotinic cholinergic transmission at the major pelvic ganglia at acute and chronic stages.We performed unilateral decentralizations by transecting pelvic and hypogastric nerves on the right side of the mouse before their point of entry to the ganglion. The left side was left intact. We employed molecular and electrophysiology techniques on sham‐surgical control and decentralized adult male Swiss Webster mice. We measured the mRNA abundance of α2, α3, α4, α5, α6, α7, β2 and β4 nicotinic receptor subunits in whole MPGs using quantitative PCR (qPCR). We then measured synaptic transmission at MPG neurons using both current and voltage clamp methods. We measured synaptic strengths by recording excitatory postsynaptic currents (EPSCs) in response to pressure ejections of acetylcholine (ACh).Our results indicate that loss of input to the MPG causes increased in synaptic strength of cholinergic neurons in both acute stage (24hours) and chronic stage (28 days) post‐injury. The increased levels were more pronounced in contralateral (intact) ganglia of the decentralized animals compared to ipsilateral (transected) ganglia at both acute and chronic stages. At 28 days post injury, the synaptic strength seems to be decreasing towards the sham‐control levels and the significant difference disappears for the contralateral ganglia. The increase in synaptic strength in decentralized ganglia were also accompanied by significant increase in mRNA transcript expression for α3 and β4 subunits. Physiological experiments involving subunit specific nicotinic acetylcholine receptor blockers suggest that α3 and β4 subunits seem to be the major subunits involved in nicotinic transmission at the mouse MPG. Hence, our study suggests that loss of input to mouse MPG results in increased in synaptic transmission of the MPG neurons and this increased level is also reflected at the level of mRNA transcript numbers for the major subunits involved in the synaptic transmission.Support or Funding InformationThis project was supported by funding from Missouri Spinal Cord Injury Research Program and Craig H. Neilsen Foundation.
Activation of N‐methyl‐D‐aspartate Receptor Inhibits Enkephalinergic Neurons in Mouse Spinal Superficial Dorsal Horn
Authors: Kato Eiko , Takemura Yu , Fukushima Teruyuki , Hori Yuuichi 
Published: November 2023

Enkephalin (Enk)‐containing neurons are distributed at high concentration in the spinal cord superficial dorsal horn (SDH), where they play an important role in the transmission and modulation of nociceptive information. Recently, we performed physiological characterization of Enk‐containing neurons identified by green fluorescent protein fluorescence expressed under the control of the preproenkephalin gene promoter. We observed that Enk‐containing neurons in the SDH express the N‐methyl‐D‐aspartate receptor (NMDAR) 2B (NR2B) subunit and large conductance calcium activated potassium (BK) channels. In the present experiments, we investigated the involvement of NMDAR and BK channels in the regulation of the activity of Enk‐containing neurons in the SDH.The experiments were performed in 5‐ to 8‐week‐old male ICR mice. Under ketamine/xylazine anesthesia, the lumbar spinal cord was dissected, and transverse slices were prepared. Tight‐seal whole‐cell recordings were obtained from neurons in the SDH. L‐glutamate (Glu) was applied by pressure ejection through a glass pipette placed near the recorded neurons. After the electrophysiological experiments, the recorded neurons were sampled, and single cell real‐time RT‐PCR was performed to analyze the expression profile of genes of interest in single SDH neurons. In some experiments, the left sciatic nerve was partially ligated, and mechanical allodynia was assessed by von Frey test.Puff‐applied Glu evoked an inward current at a holding potential of −70 mV. Depolarizing the holding potential to 0 mV, outward current of long duration appeared subsequent to initial inward current. The NMDAR antagonist AP‐V abolished the outward current. The NR2B‐selective NMDAR antagonist ifenprodil reduced the outward current. The outward current was also abolished by the selective BK channels antagonist iberiotoxin. Single cell real‐time RT‐PCR analysis revealed that the neurons generating the outward current showed a significant tendency to express BK channels α‐subunit mRNA, which is consistent with the pharmacological results of a BK channels antagonist. Furthermore, single SDH neurons expressing the preproenkephalin mRNA also expressed the BK channel α‐subunit, NR1, and NR2B subunit mRNAs. The expression of NR2B increased significantly in sciatic nerve‐ligated mice.Our results suggest that Ca2+ influx through NMDAR may activate BK channels and thus inhibit Enk‐containing neurons in the SDH. NMDAR‐mediated inhibition of Enk‐containing neurons is speculated to be one of the possible cellular mechanisms of chronic pain induced by peripheral nerve injury.
OVERWEIGHT IS ASSOCIATED WITH EXACERBATED IMPAIRMENT ON HEART RATE VARIABILITY IN OFFSPRING OF HYPERTENSIVE PARENTS
Authors: Viana Ariane , Nascimento Mário Cesar , de Paiva Júlia , dos Santos Fernando , Consolim‐Colombo Fernanda Marciano , Irigoyen Maria Cláudia , De Angelis Kátia 
Published: November 2023

Considering the high prevalence of hypertension worldwide and the changes in lifestyle, which has been associated with the increase in the prevalence of overweight and obesity, it is necessary to study the mechanisms involved in the onset of such dysfunctions. The impairment on heart rate variability (HRV) has been associated with the onset of cardiovascular diseases and mortality. RedIn this sense, the objective of the present study is to evaluate cardiovascular and metabolic parameters and HRV in overweight individuals with and without family history of hypertension. This is a cross‐sectional study involving overweight sedentary men (24.9 ± 4.60 years old) with (OHT, n = 14) or without (ONT n = 10) familial history of hypertension. The body mass index (BMI) and skinfolds were evaluated. Blood lipid profile, fasting glucose and glycated hemoglobin (Hb1Ac) were analyzed. The blood pressure (BP) was measured by the auscultatory method. The RR interval was recorded during a 20 minute period at rest using a frequencimeter (Polar® RS800 model). The HRV was evaluated in the time and frequency domain. Both groups presented overweight (OHT: 30.4 ± 3.8kg/m2 and ONT: 27.7 ± 2.4 kg/m2) and elevated percent of fat mass (OHT: 34.7 ± 11.5% and ONT: 29.9 ± 9.7%). Lipid and glucose profiles were in normal range in both groups; however, the OHT group presented higher HB1Ac when compared to ONT group (5.4 ± 0.38 vs. 4.9 ± 0.32%, respectively). A negative correlation was obtained in the OHT group with respect to HDL and BMI (r2 = 0.81, p = 0.0028). Systolic (OHT: 121.1 ± 11.2 vs. ONT: 119.6 ± 5.9 mmHg) and diastolic BP (OHT: 75.5 ± 9.6 vs. ONT 77.7 ± 7.5mmHg) were similar between groups. We observed a decrease of the cardiac parasympathetic modulation (HF nu = 30.5 ± 7.2 vs. 47.43 ± 9.2%), an increase in cardiac sympathetic modulation (LF nu = 69.5 ± 7.2 vs. 52.5 ± 9.2%) and higher cardiac sympathovagal balance (3.73 ± 1.8 vs. 1.74 ± 0.75) in the OHT vs. ONT group. We conclude that family history of hypertension is associated with early metabolic and HRV dysfunctions in overweight individuals, suggesting higher predisposition to hypertension onset in this population.Support or Funding InformationUNINOVE, CAPES‐PROSUP, CNPq.
The Effect of Transcranial Magnetic Stimulation on the Autonomic Nervous System in Pediatric Stroke
Authors: Chantigian Daniel , Rich Tonya , Chen Chao‐Ying , Lixandrao Maira , Gillick Bernadette , Keller‐Ross Manda 
Published: November 2023

Transcranial Magnetic Stimulation (TMS) is used to study neurodevelopmental disorders including pediatric hemiparesis secondary to perinatal stroke and periventricular leukomalacia. Case reports of vasovagal syncope with TMS in adults and children suggest that TMS may have an effect on the autonomic nervous system (ANS); however, the effect of TMS on the ANS in children with stroke is unknown.ObjectiveDetermine blood pressure (BP) and heart rate (HR) responses to single‐pulse TMS in children with perinatal stroke and periventricular leukomalacia resulting in hemiparesis.MethodsAs a part of a larger study, autonomic data was recorded from 16 participants (9 females, 13 ± 4 yrs, mean ± SD) at rest and during resting motor threshold (RMT) testing of the primary motor cortex. RMT testing occurred for 15 ± 11 minutes. HR was continuously recorded via a 3‐lead electrocardiogram and BP was continuously recorded via a finger plethysmography device (AD Instruments, Colorado Springs, CO). Eight participants were excluded from the BP analysis because of unreliable data due to spasticity (n=5) and a lack of correct finger cuff size (n=3) in the monitoring hand. Autonomic data recorded during the first five stimulations were averaged and defined as the beginning of the stimulation session, while data recorded during the last five stimulations were averaged and defined as the end of the stimulation session.ResultsAverage HR was similar at rest (85 ± 12 bpm) compared with the beginning of the stimulation session (82 ± 12 bpm, p = 0.06) and the end of the stimulation session (82 ± 9 bpm, p = 0.06). Average mean arterial pressure (MAP) was also similar at rest (79 ± 5 mmHg) compared with the beginning of the stimulation session (83 ± 7 mmHg, p = 0.29) and the end of the stimulation session (87 ± 18 mmHg, p = 0.24). Individual responses to TMS administration were variable and ranged from −17 to + 5 bpm for HR and from − 9 to + 32 mmHg for MAP.ConclusionAlthough on average TMS did not alter HR and BP in children with stroke, variations in individual responses to TMS were observed, suggesting that the ANS in some individuals might be more responsive to TMS administration than others. It is unclear if the observed changes in individual responses are a direct result of the stimulation or due to anticipation of receiving TMS (e.g. anxiety or stress). Because of the variations in individual HR and BP responses to TMS administration, monitoring the ANS may be important for identifying individuals that are at risk for syncopal events.
ESRD Patients Have Altered Pattern of Heart Rate Variability Responses to Graded Lower Body Negative Pressure
Authors: Ye Kara , Downey Ryan , Liao Peizhou , Park Jeanie 
Published: November 2023

End stage renal disease (ESRD) patients have autonomic neuropathy that contributes to increased cardiovascular (CV) risk. The normal autonomic response to orthostatic stress induced by hypovolemia is to increase sympathetic nervous system (SNS) and decrease parasympathetic nervous system (PNS) activation in order to maintain arterial blood pressure. Prior studies have shown that healthy individuals have decreases in heart rate variability (HRV) in response to increased orthostatic stress induced by graded lower body negative pressure (LBNP), reflective of increased SNS and decreased PNS activation to the heart in response to central hypovolemia. The objective of this study was to determine if ESRD patients have intact HRV responses during orthostatic stress. Given that ESRD patients have autonomic neuropathy, we hypothesized that ESRD patients have lower HRV at baseline, and an inability to adjust SNS and PNS activity to the heart in response to orthostatic stress. We measured continuous beat‐to‐beat blood pressure and ECG at baseline for 10 minutes, and during orthostatic stress induced via increasing doses of LBNP (−5, −10, −15, −20, −30, and −40 mmHg) applied for 3 minutes at each dose in ESRD patients and healthy controls. HRV was quantified as: 1)the standard deviation of the normal R‐R interval (SDNN), which is reflective of total autonomic activity; 2) the root mean square of the successive differences between adjacent N‐N intervals (RMSSD), and 3) percentage of adjacent NN intervals that differ by greater than 50 msec (pNN50), which are primarily reflective of PNS activity to the heart. We observed that baseline SDNN (p=0.001), RMSSD (p=0.004), and pNN50 (p=0.016) were significantly lower in ESRD patients compared to healthy controls, suggestive of chronically high SNS and low PNS activity in ESRD patients. The slopes of change in RMSSD and pNN50 with increasing LBNP were significantly different between ESRD and controls (p=0.004 and p<0.001, respectively). Whereas healthy controls exhibited gradual decreases in RMSSD and pNN50 with increasing LBNP, signifying decreasing PNS activity to the heart during orthostatic stress, ESRD patients exhibited constant and unchanging RMSSD and pNN50 values, suggesting failure to adjust PNS activity to the heart during orthostatic stress. In conclusion, ESRD patients had low baseline HRV measurements, indicative of high SNS and low PNS activity that could contribute to cardiovascular complications in this population. Unlike controls, ESRD patients did not demonstrate a withdrawal of PNS activation to the heart during orthostatic stress. Failure to adjust autonomic responses during orthostatic stress in ESRD may contribute to orthostatic intolerance and increased CV risk in this patient population.Support or Funding InformationSupported by NIH HL‐098744, NIH DK‐101390, VA Merit I01CX001065, and Satellite Healthcare, a not‐for‐profit renal care provider.
Sympathetic and phrenic nerve activities in the offspring of high fat diet feeding dams
Authors: Amaral Nathalia Oda , Bassi Mirian , Sa Jessica M , Barbosa Rafaela Moreira , Zoccal Daniel , Menani Jose , Colombari Eduardo , Pedrino Gustavo , Colombari Débora Simoes Almeida 
Published: November 2023

It has been demonstrated that juvenile offspring (P30) of high fat diet (HFD) feeding dams presented elevated levels of arterial pressure, probably due to a higher sympathetic nerve activity (SNA) (Hypertension, 55: 76, 2010). In the present study, we evaluated baseline and baro‐/chemoreflex control of SNA and phrenic nerve (PN) activity in offspring of HFD feeding dams. We also investigated the brain regions responsible for the maintenance of the SNA in these animals. Female rats (280–300 g) were fed with standard diet (SD) or HFD from the 6 weeks before mating until the end of lactation. After weaning (P21), the offspring were fed with SD. At P28–P32, the males of the SD‐offspring (SD‐O, n=11) or HFD‐O (n=7) underwent the in situ working‐heart‐brainstem‐hypothalamus preparation to analyze SNA and PN amplitude and frequency at baseline conditions and during chemoreflex (0.05% KCN; 50 μl) or baroreflex (0.01% phenylephrine; 100 μl) activation. At the end of the experiments a pre‐collicular transection was performed and the changes in SNA and PN activity were evaluated. We observed that there was no change in baseline SNA or PN frequency and amplitude between groups. HFD‐O showed reduced sympatho‐excitatory response to KCN compared to SD‐O (52.1 ± 10.2, vs. SD‐O: 107.3 ± 15.1%; p<0.05), greater increase in PN burst amplitude (31.8 ± 10.4 vs. SD‐O: 14.3 ± 4.1%; p<0.05) and no changes in the tachypneic response. In addition, the sympathoinhibitory response to baroreflex stimulation was decreased in HFD‐O compared to SD‐O (−32 ± 5.1%, vs. SD‐O: −56 ± 3%; p < 0.05). After the pre‐collicular transection, a significant decrease in SNA was noted in SD‐O (−28,2 ± 4,9 %, vs. baseline, p < 0.05), but not in the HFD‐O group (8.3 ± 10.9%, vs. baseline; p>0.05). There was no change in PN activity after pre‐collicular transection. The data demonstrate that in HFD‐O there is an impairment of the baroreflex and chemoreflex control of SNA. Furthermore, the SNA maintenance in these offspring seems to depend mostly on the brainstem. We still need to determine whether these changes can be responsible for the higher blood pressure levels observed in the juvenile HFD‐O rats.Support or Funding InformationCNPq (304873/2014‐4), CAPES e FAPESP (2015/23467‐7)
Does temporary inhibition of the human primary motor cortex alter resting and isometric handgrip exercise‐mediated sympathetic neural responses?
Authors: Kimmerly Derek S. , Boe Shaun , Ladouceur Michel , Weir Julie A. 
Published: November 2023

Resting muscle sympathetic nerve activity (MSNA) is elevated in stroke patients with damage encompassing the primary motor cortex (M1) and during single‐pulse, inhibitory transcranial magnetic stimulation (TMS) protocols over M1 in healthy participants. These findings suggest a suppressive role of M1 on resting levels of MSNA. It is currently unclear whether inhibition of M1 alters resting and/or exercise‐mediated sympathetic activity in humans. We tested the hypothesis that temporary inhibition of the contralateral hand region of M1 would exaggerate resting and isometric handgrip exercise (IHG)‐mediated MSNA. 12 (7♀) young, healthy (23±3 years, 25±3 kg•m−2) participants were instrumented for recordings of fibular MSNA (microneurography), heart rate (HR, electrocardiography), and non‐invasive blood pressure (BP, Portapres®). These measures were collected at rest, during 2 minutes of IHG (35% maximum effort) and 2 minutes of post‐exercise ischemia (PEI). This protocol was repeated under the following theta burst TMS (TBS) conditions: Sham (no TBS), continuous TBS (cTBS, Inhibitory) and intermittent TBS (iTBS, Facilitatory). Sham was always performed first followed by randomly assigned cTBS and iTBS conditions. Compared to Sham (30±7 bursts•100 heartbeats−1), MSNA burst incidence was higher (p<0.02) five minutes following cTBS (42±13 bursts•100 heartbeats−1) but unchanged (p=0.49) after iTBS (30±12 bursts•100 heartbeats−1). Resting HR and mean arterial BP (MAP) recorded during Sham were unchanged (all, p>0.51) following iTBS and cTBS. From rest, MSNA increased (p<0.05) after IHG (38±9 bursts•minute−1) and remained elevated following PEI (37±8 bursts•minute−1) during the Sham condition. Furthermore, HR and MAP responses peaked (both, p < 0.01) after 2‐minutes of IHG but returned to resting levels following PEI. These MSNA and cardiovascular responses to IHG and PEI were not different (all, p>0.37) in the cTBS and iTBS conditions. In conclusion, temporary inhibition of the hand region in M1 via cTBS produced a transient sympathoexcitation but did not alter resting HR or MAP. Neither facilitatory (iTBS) nor inhibitory (cTBS) stimulation protocols altered IHG‐mediated sympathetic or cardiovascular reflex responses. These findings warrant future investigation aimed at determining whether cTBS protocols can reduce resting MSNA in patient populations characterized by exaggerated sympathoexcitation (e.g., resistant hypertension, ischemic stroke).Support or Funding InformationSupport provided by: Canadian Foundation for Innovation: Leaders Opportunity Fund
Identification of Stress‐Activated Inputs to the Dorsomedial Hypothalamus
Authors: Prestipino Louise , Ouro Emily A , Jayaratne Sachini K , Polson Jaimie W 
Published: November 2023

Acute psychological stress elicits a typical response characterized in the short term by elevated sympathetic nerve activity and increases in heart rate and blood pressure. While the primary neural circuitry that underpins these responses is still uncertain, the dorsomedial hypothalamus (DMH) is known to play a major role.1 However, the antecedent inputs responsible for DMH activation in response to stress are unknown. In the present study, retrograde tracing was combined with Fos immunohistochemistry following air jet stress (AJS) to identify neurons that both project to the DMH and are activated by stress.Sprague Dawley rats received a unilateral injection of 15–30 nl of retrograde tracer choleratoxin B subunit‐AlexaFluor 555 into the DMH. One week later rats were exposed to a 15 minute AJS protocol (n=4), while controls (n=2) were left undisturbed. Following perfusion, brain sections were processed for Fos immunohistochemistry and photographed. The distribution of retrogradely and/or Fos‐labeled neurons was mapped using a rat brain atlas.2 The number of labeled cells in key regions was counted. Data are expressed as mean ± SE cells per section.Retrogradely labeled neurons were found throughout the brainstem and forebrain (Table 1). The majority of labeled cells were located in the forebrain, in particular in the medial prefrontal cortex, lateral septal nucleus, claustrum and amygdala. Following AJS, Fos‐positive neurons were located in many, but not all, of the regions in which retrogradely labeled neurons were found. There was a significant increase in the number of Fos‐positive neurons in the Kolliker Fuse nucleus (KF) in the pons, the dorsomedial, dorsolateral and ventrolateral midbrain periaqueductal gray (PAG), amygdala, the cingulate cortex, lateral septal nucleus and the claustrum. Double‐labeled neurons were found in the brainstem in the KF and ventrolateral PAG, and in the forebrain in the amygdala, cingulate cortex, lateral septal nucleus and claustrum. However, overall there were very few double‐labeled neurons seen throughout the brain.Neurons that both project to the DMH and are activated by AJS were identified in several brain regions, particularly in the forebrain. The number of such neurons was very small, suggesting that these neurons may play a minor role in stress‐induced activation of the DMH. An alternate hypothesis is that recruitment of DMH in response to stress may be dependent upon disinhibition.
Number of labeled cells in key nuclei

Region
CTb
Fos
CTb + Fos

RVLM
0.7±0.4
9.2±5.1
0.0±0

RVMM
0.3±0.2
6.1±4
0.0±0

PBC
27.6±14.2
14.4±5.9
1.5±0.8

KF
20.2±14.8
11.0±4.0*
0.6±0.4*

dmPAG
4.4±2.1
7.3±1*
0.2±0.2

dIPAG
4.2±1.5
10.7±0.6*
0.5±0.4

IPAG
8.6±2.7
19.9±2.4
0.3±0.1

vIPAG
12.0±1.6
18.4±3.2*
1.0±0.5*

Amy
124.4±22.7
55.9±18.3*
2.4±0.7*

Cingular Cor
88.8±32.1
17.0±0.3*
3.2±0.8*

Lat SN
177.9±62.1
38.5±5.5*
4.9±1.8*

Claustrum
148.3±55.2
35.8±11*
2.1±0.4*

mPFC
192.0±79
42.4±21.1
3.3±0.8

Values are mean ± SE