Motor Nucleus Research Articles

The Role of the Vagus Nerve in the Microbiome and Digestive System in Relation to Epilepsy.

The Enteric Nervous System (ENS) is described as a division of the Peripheral Nervous System (PNS), located within the gut wall and it is formed by two main plexuses: the myenteric plexus (Auerbach's) and the submucosal plexus (Meissner's). The contribution of the ENS to the pathophysiology of various neurological diseases such as Parkinson's or Alzheimer's disease has been described in the literature, while some other studies have found a connection between epilepsy and the gastrointestinal tract. The above could be explained by cholinergic neurons and neurotransmission systems in the myenteric and submucosal plexuses, regulating the vagal excitability effect. It is also understandable, as the discharges arising in the amygdala are transmitted to the intestine through projections the dorsal motor nucleus of the vagus, giving rise to efferent fibers that stimulate the gastrointestinal tract and consequently the symptoms at this level. Therefore, this review's main objective is to argue in favor of the existing relationship of the ENS with the Central Nervous System (CNS) as a facilitator of epileptogenic or ictogenic mechanisms. The gut microbiota also participates in this interaction; however, it depends on many individual factors of each human being. The link between the ENS and the CNS is a poorly studied epileptogenic site with a big impact on one of the most prevalent neurological conditions such as epilepsy.

Olfactory and trigeminal routes of HSV-1 CNS infection with regional microglial heterogeneity.

Herpes simplex virus type 1 (HSV-1) primarily targets the oral and nasal epithelia before establishing latency in the trigeminal ganglion (TG) and other peripheral ganglia. HSV-1 can also infect and become latent in the central nervous system (CNS) independent of latency in the TGs. Recent studies suggest entry to the CNS via two distinct routes: the TG-brainstem connection and olfactory nerve; however, to date, there is no characterization of brain regions targeted during HSV-1 primary infection. Furthermore, the immune response by microglia may also contribute to the heterogeneity between different brain regions. However, the response to HSV-1 by microglia has not been characterized in a region-specific manner. This study investigated the time course of HSV-1 spread within the olfactory epithelium (OE) and CNS following intranasal inoculation and the corresponding macrophage/microglial response in a C57BL/6 mouse model. We found an apical to basal spread of HSV-1 within the OE and underlying tissue accompanied by an inflammatory response of macrophages. OE infection was followed by infection of a small subset of brain regions targeted by the TG in the brainstem and other cranial nerve nuclei, including the vagus and hypoglossal nerve. Furthermore, other brain regions were positive for HSV-1 antigens, such as the locus coeruleus (LC), raphe nucleus (RaN), and hypothalamus while sparing the hippocampus and cortex. Within each brain region, microglia activation also varied widely. These findings provide critical insights into the region-specific dissemination of HSV-1 within the CNS, elucidating potential mechanisms linking viral infection to neurological and neurodegenerative diseases.IMPORTANCEThis study shows how herpes simplex virus type 1 (HSV-1) spreads within the brain after infecting the nasal passages. Our data reveal the distinct pattern of HSV-1 through the brain during a non-encephalitic infection. Furthermore, microglial activation was also temporally and spatially specific, with some regions of the brain having sustained microglial activation even in the absence of viral antigens. Previous reports have identified specific brain regions found to be positive for HSV-1 infection; however, to date, there has not been a concise investigation of the anatomical spread of HSV-1 and the brain regions consistently vulnerable to viral entry and spread. Understanding these region-specific differences in infection and immune response is crucial because it links HSV-1 infection to potential triggers for neurological and neurodegenerative diseases.

The development of hepatic steatosis depends on the presence of liver-innervating parasympathetic cholinergic neurons in mice fed a high-fat diet.

Hepatic lipid metabolism is regulated by the autonomic nervous system of the liver, with the sympathetic innervation being extensively studied, while the parasympathetic efferent innervation is less understood despite its potential importance. In this study, we investigate the consequences of disrupted brain-liver communication on hepatic lipid metabolism in mice exposed to obesogenic conditions. We found that a subset of hepatocytes and cholangiocytes are innervated by parasympathetic nerve terminals originating from the dorsal motor nucleus of the vagus. The elimination of the brain-liver axis by deleting parasympathetic cholinergic neurons innervating the liver prevents hepatic steatosis and promotes browning of inguinal white adipose tissue (ingWAT). The loss of liver-innervating cholinergic neurons increases hepatic Cyp7b1 expression and fasting serum bile acid levels. Furthermore, knockdown of the G protein-coupled bile acid receptor 1 gene in ingWAT reverses the beneficial effects of the loss of liver-innervating cholinergic neurons, leading to the reappearance of hepatic steatosis. Deleting liver-innervating cholinergic neurons has a small but significant effect on body weight, which is accompanied by an increase in energy expenditure. Taken together, these data suggest that targeting the parasympathetic cholinergic innervation of the liver is a potential therapeutic approach for enhancing hepatic lipid metabolism in obesity and diabetes.

Signals from the dorsal motor nucleus of the vagus promote jejunal fat absorption.

Signals from the dorsal motor nucleus of the vagus promote jejunal fat absorption.

The area postrema: a critical mediator of brain-body interactions.

The dorsal vagal complex contains three structures: the area postrema, the nucleus tractus solitarii, and the dorsal motor nucleus of the vagus. These structures are tightly linked, both anatomically and functionally, and have important yet distinct roles in not only conveying peripheral bodily signals to the rest of the brain but in the generation of behavioral and physiological responses. Reports on the new discoveries in these structures were highlights of the symposium. In this outlook, we focus on the roles of the area postrema in mediating brain-body interactions and its potential utility as a therapeutic target, especially in cancer cachexia.

Trigeminal cervical complex: A neural network affecting the head and neck

ObjectivesTo introduce the trigeminal cervical complex (TCC) as a comprehensive framework for understanding the anatomical and functional scope of the afferences and efferences of the trigeminal nerve and explaining common otolaryngologic symptoms, including head and neck myofascial pain syndrome. Additionally, it explores how the bidirectional transmission of neurotransmitters contributes to the sensitization of the TCC and motor nuclei. MethodsThe study was conducted as a narrative review. The authors performed a comprehensive search of multiple databases, including Medline/OVID, Embase, Scopus, and PubMed, covering publications from inception until August 2023. Both keywords and medical subject headings related to the TCC were utilized in the search. Information from 66 studies was extracted based on predetermined inclusion and exclusion criteria. ResultsThis review discusses the multiple afferent connections from cranial nerves, specifically VII, IX, X, and XI, to the TCC, and their respective efferent pathways. These connections may explain various clinical manifestations in the head and neck that cannot be attributed to other medical conditions. Additionally, the review highlights the dual sensory and motor nature of cranial nerves, emphasizing the bidirectional transmission of neurotransmitters in head and neck areas, which leads to the sensitization of both the TCC and motor nuclei innervating the cervicofacial muscles. ConclusionThe authors hypothesize that the central and peripheral sensitization and the intricate connections of the TCC can elucidate the pathophysiology of conditions such as otalgia, tinnitus, hearing loss, vertigo, headache, cervicogenic dizziness, bruxism, and other symptoms affecting the head and neck.

The development of hepatic steatosis depends on the presence of liver-innervating parasympathetic cholinergic neurons in mice fed a high-fat diet.

Hepatic lipid metabolism is regulated by the autonomic nervous system of the liver, with the sympathetic innervation being extensively studied, while the parasympathetic efferent innervation is less understood despite its potential importance. In this study, we investigate the consequences of disrupted brain-liver communication on hepatic lipid metabolism in mice exposed to obesogenic conditions. We found that a subset of hepatocytes and cholangiocytes are innervated by parasympathetic nerve terminals originating from the dorsal motor nucleus of the vagus. The elimination of the brain-liver axis by deleting parasympathetic cholinergic neurons innervating the liver prevents hepatic steatosis and promotes browning of inguinal white adipose tissue (ingWAT). The loss of liver-innervating cholinergic neurons increases hepatic Cyp7b1 expression and fasting serum bile acid levels. Furthermore, knockdown of the G protein-coupled bile acid receptor 1 gene in ingWAT reverses the beneficial effects of the loss of liver-innervating cholinergic neurons, leading to the reappearance of hepatic steatosis. Deleting liver-innervating cholinergic neurons has a small but significant effect on body weight, which is accompanied by an increase in energy expenditure. Taken together, these data suggest that targeting the parasympathetic cholinergic innervation of the liver is a potential therapeutic approach for enhancing hepatic lipid metabolism in obesity and diabetes.

Anatomic and functional evidence for renal autonomic innervation in normotensive and hypertensive rats.

Renal denervation (RDN) has been used for treating resistant hypertension. A few recent studies have shown vagal innervation of kidneys causing confusion. This study aimed to provide anatomical and functional evidence for renal autonomic innervation. Experiments were performed in male Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Pseudorabies virus (PRV) in the paraventricular nucleus and rostral ventrolateral medulla was prevented by bilateral RDN, but not subdiaphragmatic vagotomy. PRV did not appear in the dorsal motor nucleus of the vagus and nucleus tractus solitarii 72 h after renal injection of PRV. Adrenergic fibers were approximately seven times more than cholinergic fibers in the main renal artery (MRA) and its first (1RA) and second grade (2RA) branches. Adrenergic fibers in 1RA were more than those in MRA and 2RA. Tyrosine hydroxylase immunoreactivity in these arteries was higher in SHR than in WKY. Norepinephrine (NE) increased and α-receptor antagonist reduced vascular ring tension of renal arteries. The effect of NE was greater in 1RA and 2RA than in MRA, which was prevented by α-receptor antagonist. Acetylcholine (ACh) or blockage of β-receptors, M receptors, or N receptors had no significant effects on vascular ring tension and the effect of NE. Renal blood flow was reduced by electrical stimulation of renal nerves but not affected by stimulation of the subdiaphragmatic vagus. These results provide anatomical and functional evidence that kidneys are innervated and renal blood flow is regulated by renal sympathetic nerves rather than the vagus. Renal vasoconstriction is regulated by NE and adrenergic fibers rather than ACh or cholinergic fibers in WKY and SHR.NEW & NOTEWORTHY Kidneys are innervated by renal nerves rather than the vagus. Adrenergic fibers in renal arteries are about seven times more than cholinergic fibers. Renal vasoconstriction is regulated by norepinephrine and adrenergic fibers rather than acetylcholine or cholinergic fibers. Renal blood flow is regulated by renal sympathetic nerves and is not affected by the vagus. These findings provide anatomical and functional evidence for renal autonomic innervation in normotensive and hypertensive rats.

A brain-to-gut signal controls intestinal fat absorption.

Although fat is a crucial source of energy in diets, excessive intake leads to obesity. Fat absorption in the gut isprevailingly thought to occurorgan-autonomously by diffusion1-3. Whether the process is controlled by the brain-to-gut axis, however, remains largely unknown. Here we demonstrate that the dorsal motor nucleus of vagus (DMV) plays a key part in this process. Inactivation of DMV neurons reduces intestinal fat absorption and consequently causes weight loss, whereas activation of the DMV increases fat absorption and weight gain. Notably, the inactivation of a subpopulation of DMV neurons that project to the jejunum shortens the length of microvilli, thereby reducing fat absorption. Moreover, we identify a natural compound, puerarin, that mimics the suppression of the DMV-vagus pathway, which in turn leads to reducedfat absorption. Photoaffinity chemical methods and cryogenic electron microscopy of the structure of a GABAA receptor-puerarin complex reveal that puerarin binds to an allosteric modulatory site. Notably, conditional Gabra1 knockout in the DMV largely abolishes puerarin-induced intestinal fat loss. In summary, we discover that suppression of the DMV-vagus-jejunum axis controls intestinal fat absorption by shortening the length of microvilli and illustrate the therapeutic potential of puerarin binding to GABRA1 in fat loss.

Effect of Mucuna pruriens seed extract on depression-like behavior derived from mild traumatic brain injury in rats.

Traumatic brain injury (TBI) is a severe health problem for which there is no specific treatment, leading to neurological or neuropsychological consequences. One of the most described disorders, even after mild TBI (mTBI), is depression, related to mechanisms involving reactive oxygen species (ROS). The Mucuna pruriens (M. pruriens) plant has various antioxidant, neuroprotective, and anti-inflammatory properties. There is insufficient evidence of M. pruriens use for the treatment of neurobehavioral and depressive impairments induced by TBI and of the mechanisms underlying this effect, so we aimed to evaluate the ability of shortterm administration of M. pruriens extract to prevent neurobehavioral impairment and depression-like behaviors in a murine model of mTBI as well as evaluate the role of oxidative stress. Male Wistar rats underwent mTBI or sham surgery. Immediately after, they were treated with vehicle or M. pruriens extract (50 mg/kg ip/day for five days). We evaluated neurobehavioral recovery using the Neurobehavioral Severity Scale-Revised (NSS-R) and the immobility time in the forced swimming test 3, 7, 15, 30, and 60 days after mTBI. In addition, lipid peroxidation (LP) and GSH concentrations were determined in some brain areas (motor cortex, striatum, midbrain, and nucleus accumbens). M. pruriens extract did not decrease neurobehavioral impairment caused by mTBI. Nevertheless, it prevented depression-like behaviors starting three days after mTBI, reduced LP, and increased GSH in some brain areas. Conclusions: M. pruriens may prevent depression-like behaviors and reduce oxidative stress by decreasing LP and increasing concentrations of antioxidant compounds.

A high-fat diet influences neural stem and progenitor cell environment in the medulla of adult mice

It has been widely established that neural stem cells (NSCs) exist in the adult mammalian brain. The area postrema (AP) and the ependymal cell layer of the central canal (CC) in the medulla were recently identified as NSC niches. There are two types of NSCs: astrocyte-like cells in the AP and tanycyte-like cells in the CC. However, limited information is currently available on the characteristics and functional significance of these NSCs and their progeny in the AP and CC. The AP is a part of the dorsal vagal complex (DVC), together with the nucleus of the solitary tract (Sol) and the dorsal motor nucleus of the vagus (10 N). DVC is the primary site for the integration of visceral neuronal and hormonal cues that act to inhibit food intake. Therefore, we examined the effects of high-fat diet (HFD) on NSCs and progenitor cells in the AP and CC. Eight-week-old male mice were fed HFD for short (1 week) and long periods (4 weeks). To detect proliferating cells, mice consecutively received intraperitoneal injections of BrdU for 7 days. Brain sections were processed with immunohistochemistry using various cell markers and BrdU antibodies. Our data demonstrated that adult NSCs and neural progenitor cells (NPCs) in the medulla responded more strongly to short-term HFD than to long-term HFD. HFD increased astrocyte density in the Sol and 10 N, and increased microglial/macrophage density in the AP and Sol. Furthermore, long-term HFD induced mild inflammation in the medulla, suggesting that it affected the proliferation of NSCs and NPCs.

Comprehensive Morphometric Analysis of the Rhomboid Fossa: Implications for Safe Entry Zones in Brainstem Surgery

The rhomboid fossa (RF) is a crucial anatomical region in brainstem surgery, as it contains essential structures like the reticular formation and cranial nerve nuclei. This study aims to provide a detailed understanding of the RF's complex microsurgical anatomy, which is vital for the safe execution of neurosurgical procedures. Morphometric analysis was conducted on 45 adult human brainstems preserved in 10% formalin. Thirteen linear measurements were performed under 20x magnification, using a millimeter graph to identify key anatomical landmarks. The study provided precise measurements of the rhomboid fossa, with a length of 34.65 mm and a width of 22.61 mm. The facial colliculus (FC) measured 4.26 mm in length on the left and 4.45 mm on the right, with corresponding widths of 3.77 mm and 3.50 mm. The distance between the sulcus limitans incisures was 9.52 mm, while the distance from the upper border of the medullary striae to obex was 11.53 mm. The proximity of the FC to the median sulcus was measured at 0.86 mm on the right and 0.96 mm on the left. Additionally, two safe entry zones-the suprafacial and infrafacial triangles-were identified, offering pathways to reach dorsal pons lesions through the RF. This comprehensive morphometric analysis of the RF enhances the understanding of its intricate anatomy. By describing safe entry zones, the suprafacial and infrafacial triangles, and providing precise measurements of key anatomical features, this research serves as a valuable resource for neurosurgeons in planning and executing brainstem surgeries.

Neuromodulatory co-expression in cardiac vagal motor neurons of the dorsal motor nucleus of the vagus

Vagal innervation is well known to be crucial to the maintenance of cardiac health, and to protect and recover the heart from injury. Only recently has this role been shown to depend on the activity of the underappreciated dorsal motor nucleus of the vagus (DMV). By combining neural tracing, transcriptomics, and anatomical mapping in male and female Sprague-Dawley rats, we characterize cardiac-specific neuronal phenotypes in the DMV. We find that the DMV cardiac-projecting neurons differentially express pituitary adenylate cyclase-activating polypeptide (PACAP), cocaine- and amphetamine-regulated transcript (CART), and synucleins, as well as evidence that they participate in neuromodulatory co-expression involving catecholamines. The significance of these findings is enhanced by previous knowledge of the role of PACAP at the heart and of the other neuromodulators in peripheral vagal targets.

Respiratory neuropathology in spinocerebellar ataxia type 7.

Spinocerebellar ataxia type 7 (SCA7) is an autosomal dominant neurological disorder caused by deleterious CAG repeat expansion in the coding region of the ataxin 7 gene (polyQ-ataxin-7). Infantile-onset SCA7 leads to severe clinical manifestation of respiratory distress, but the exact cause of respiratory impairment remains unclear. Using the infantile-SCA7 mouse model, the SCA7266Q/5Q mouse, we examined the impact of pathological polyQ-ataxin-7 on hypoglossal (XII) and phrenic motor units. We identified the transcript profile of the medulla and cervical spinal cord and investigated the XII and phrenic nerves and the neuromuscular junctions in the diaphragm and tongue. SCA7266Q/5Q astrocytes showed significant intranuclear inclusions of ataxin-7 in the XII and putative phrenic motor nuclei. Transcriptomic analysis revealed dysregulation of genes involved in amino acid and neurotransmitter transport and myelination. Additionally, SCA7266Q/5Q mice demonstrated blunted efferent output of the XII nerve and demyelination in both XII and phrenic nerves. Finally, there was an increased number of neuromuscular junction clusters with higher expression of synaptic markers in SCA7266Q/5Q mice compared with WT controls. These preclinical findings elucidate the underlying pathophysiology responsible for impaired glial cell function and death leading to dysphagia, aspiration, and respiratory failure in infantile SCA7.

Indole induces anxiety-like behaviour in mice mediated by brainstem locus coeruleus activation

The gut microbiota produces metabolites that enrich the host metabolome and play a part in host physiology, including brain functions. Yet the biological mediators of this gut-brain signal transduction remain largely unknown. In this study, the possible role of the gut microbiota metabolite indole, originating from tryptophan, was investigated. Oral administration of indole to simulate microbial overproduction of this compound in the gut consistently led to impaired locomotion and anxiety-like behaviour in both C3H/HeN and C57BL/6J mice. By employing c-Fos protein expression mapping in mice, we observed a noticeable increase in brain activation within the dorsal motor nucleus of the vagus nerve (DMX) and the locus coeruleus (LC) regions in a dose-dependent manner. Further immune co-labelling experiments elucidated that the primary cells activated within the LC were tyrosine hydroxylase positive. To delve deeper into the mechanistic aspects, we conducted chemogenetic activation experiments on LC norepinephrine neurons with two doses of clozapine N-oxide (CNO). Low dose of CNO at 0.5 mg/kg induced no change in locomotion but anxiety-like behaviour, while high dose of CNO at 2 mg/kg resulted in locomotion impairment and anxiety-like behaviour. These findings support the neuroactive roles of indole in mediating gut-brain communication. It also highlights the LC as a novel hub in the gut-brain axis, encouraging further investigations.

The parasympathetic and sensory innervation of the proximal and distal colon in male mice.

The distributions of extrinsic neurons innervating the colon show differences in experimental animals from humans, including the vagal and spinal parasympathetic innervation to the distal colon. The neuroanatomical tracing to the mouse proximal colon has not been studied in details. This study aimed to trace the locations of extrinsic neurons projecting to the mouse proximal colon compared to the distal colon using dual retrograde tracing. The parasympathetic and sensory neurons projecting to colon were assessed using Cholera Toxin subunit B conjugated to Alexa-Fluor 488 or 555 injected in the proximal and distal colon of the same mice. Retrograde tracing from the proximal and distal colon labeled neurons in the dorsal motor nucleus of the vagus (DMV) and the nodose ganglia, while the tracing from the distal colon did not label the parasympathetic neurons in the lumbosacral spinal cord at L6-S1. Neurons in the pelvic ganglia which were cholinergic projected to the distal colon. There were more neurons in the DMV and nodose ganglia projecting to the proximal than distal colon. The right nodose ganglion had a higher number of neurons than the left ganglion innervating the proximal colon. In the dorsal root ganglia (DRG), the highest number of neurons traced from the distal colon were at L6, and those from the proximal colon at T12. DRG neurons projected closely to the cholinergic neurons in the intermediolateral column of L6 spinal cord. Small percentages of neurons with dual projections to both the proximal and distal colon existed in the DMV, nodose ganglia and DRG. We also observed long projecting neurons traced from the caudal distal colon to the transverse and proximal colon, some of which were calbindin immunoreactive, while there were no retrogradely labeled neurons traced from the proximal to distal colon. These data demonstrated that the vagal motor and motor and sensory neurons innervate both the proximal and distal colon in mice, and the autonomic neurons in the intermediate zone of the lumbosacral spinal cord do not project directly to the mouse colon, which differs from that in humans.

Effect of sex on chronic stress induced alterations in hindbrain catecholaminergic system and autonomic dysfunction resulting in gastrointestinal dysmotility

It has been reported that the clinical symptoms of functional dyspepsia (FD) exacerbate upon stress while the gender-related factors have been incompletely understood. This study aims to investigate the role of sex in chronic heterotypic stress (CHS)-induced autonomic and gastric motor dysfunction. For CHS, the rats were exposed to the combination of different stressors for 7 consecutive days. Subsequently, electrocardiography was recorded in anesthetized rats to evaluate heart rate variability (HRV) for the determination of autonomic outflow and sympathovagal balance. Solid gastric emptying (GE) was measured in control and CHS-loaded male and female rats. The immunoreactivities of catecholaminergic cell marker tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), corticotropin releasing factor (CRF), and estrogen receptor (ER-α/β) were evaluated in medullary and pontine brainstem sections by immunohistochemistry. Compared with the controls, CHS significantly delayed GE in males but not in females. There was no significant sex-related difference in parasympathetic indicator HF under either control or CHS conditions. Sympathetic indicator LF was significantly higher in control females compared to the males. The higher sympathetic output in females was found to be attenuated upon CHS; in contrast, the elevated sympathetic output was detected in CHS-loaded males. No sex- or stress-related effect was observed on ChAT immunoreactivity in the dorsal motor nucleus of N.vagus (DMV). In males, greater number of TH-ir cells was observed in the caudal locus coeruleus (LC), while they were more densely detected in the rostral LC of females. Regardless of sex, CHS elevated immunoreactivity of TH throughout the LC. Under basal conditions, greater number of TH-ir cells was detected in the rostral ventrolateral medulla (RVLM) of females. In contrast, CHS remarkably increased the number of TH-ir cells in the RVLM of males which was found to be decreased in females. There was no sex-related alteration in TH immunoreactivity in the nucleus tractus solitarius (NTS) of control rats, while CHS affected both sexes in a similar manner. Compared with females, CRF immunoreactivity was prominently observed in control males, while both of which were stimulated by CHS. ER-α/β was found to be co-expressed with TH in the NTS and LC which exhibit no alteration related to either sex or stress status. These results indicate a sexual dimorphism in the catecholaminergic and the CRF system in brainstem which might be involved in the CHS-induced autonomic and visceral dysfunction occurred in males.

Sexual Dimorphism of Spinal Neural Circuits Controlling the Mouse External Urethral Sphincter With and Without Spinal Cord Injury.

Spinal cord injury (SCI) disrupts coordination between the bladder and the external urinary sphincter (EUS), leading to transient or permanent voiding impairment, which is more severe in males. Male versus female differences in spinal circuits related to the EUS as well as post-SCI rewiring are essential for understanding of sex-/gender-specific impairments and possible recovery mechanisms. To quantitatively assess differences between EUS circuits in males versus females and in spinal intact (SI) versus SCI animals, we retrogradely traced and counted EUS-related neurons. In transgenic ChAT-GFP mice, motoneurons (MNs), interneurons (INs), and propriospinal neurons (PPNs) were retrogradely trans-synaptically traced with PRV614-red fluorescent protein (RFP) injected into EUS. EUS-MNs in dorsolateral nucleus (DLN) were separated from other GFP+ MNs by tracing them with FluoroGold (FG). We found two morphologically distinct cell types in DLN: FG+ spindle-shaped bipolar (SB-MNs) and FG- rounded multipolar (RM-MNs) cholinergic cells. Number of MNs of both types in males was twice as large as in females. SCI caused a partial loss of MNs in all spinal nuclei. After SCI, males showed a fourfold rise in the number of RFP-labeled cells in retro-DLN (RDLN) innervating hind limbs. This suggests (a) an existence of direct synaptic interactions between spinal nuclei and (b) a post-SCI increase of non-specific inputs to EUS-MNs from other motor nuclei. Number of INs and PPNs deferred between males and females: In SI males, the numbers of INs and PPNs were ∼10 times larger than in SI females. SCI caused a twofold decrease of INs and PPNs in males but not in females.

Electroacupuncture Promotes Liver Regeneration by Activating DMV Acetylcholinergic Neurons-Vagus-Macrophage Axis in 70% Partial Hepatectomy of Mice.

Lack of liver regenerative capacity is the primary cause of hepatic failure and even mortality in patients undergoing hepatectomy, with no effective intervention strategies currently available. Therefore, identifying efficacious interventions to enhance liver regeneration is pivotal for optimizing clinical outcomes. Recent studies have demonstrated that vagotomy exerts an inhibitory effect on liver regeneration following partial hepatectomy, thereby substantiating the pivotal role played by the vagus nerve in the process of liver regeneration. In recent years, electroacupuncture (EA) has emerged as a non-invasive technique for stimulating the vagus nerve. However, EA on hepatic regeneration remains uncertain. In this study, a 70% partial hepatectomy (PH) mouse model is utilized to investigate the effects of EA on acute liver regeneration and elucidate its underlying molecular mechanisms. It is observed that EA at ST36 acutely activated cholinergic neurons in the dorsal motor nucleus of the vagus nerve (DMV), resulting in increased release of acetylcholine from hepatic vagal nerve endings and subsequent activation of IL-6 signaling in liver macrophages. Ultimately, these events promoted hepatocyte proliferation and facilitated liver regeneration. These findings provide insights into the fundamental brain-liver axis mechanism through which EA promotes liver regeneration, offering a novel therapeutic approach for post-hepatectomy liver regeneration disorders.

Genetic and environmental influences on structural brain development from childhood to adolescence: A longitudinal twin study on cortical thickness, surface area, and subcortical volume

The human brain undergoes structural development from childhood to adolescence, with specific regions in the sensorimotor, social, and affective networks continuing to grow into adulthood. While genetic and environmental factors contribute to individual differences in these brain trajectories, the extent remains understudied. Our longitudinal study, utilizing up to three biennial MRI scans (n=485), aimed to assess the genetic and environmental effects on brain structure (age 7) and development (ages 7–14) in these regions. Heritability estimates varied across brain regions, with all regions showing genetic influence (ranging from 18 % to 59 %) with additional shared environmental factors affecting the primary motor cortex (30 %), somatosensory cortex (35 %), DLPFC (5 %), TPJ (17 %), STS (17 %), precuneus (10 %), hippocampus (22 %), amygdala (5 %), and nucleus accumbens (10 %). Surface area was more genetically driven (38 %) than cortical thickness (14 %). Longitudinal brain changes were primarily driven by genetics (ranging from 1 % to 29 %), though shared environment factors (additionally) influenced the somatosensory cortex (11 %), DLPFC (7 %), cerebellum (28 %), TPJ (16 %), STS (20 %), and hippocampus (17 %). These findings highlight the importance of further investigating brain-behavior associations and the influence of enriched and deprived environments from childhood to adolescence. Ultimately, our study can provide insights for interventions aimed at supporting children's development.