GIPR signaling modulates PYY-induced hypophagia and malaise in rodents.

Circumventricular organs (CVOs), exemplified by the area postrema (AP), lack a classical blood-brain barrier (BBB) and feature expanded perivascular spaces (PVS) that support neuroimmune communication. Yet the precise localization of immune cells within CVO PVS, and the tempo of their reorganization under systemic metabolic stress, remain unclear. We used three-dimensional multiplex immunofluorescence and immunoelectron microscopy to map Iba1-positive cells relative to laminin-positive basement membranes and CD31-positive vessels, and applied P2RY12 immunostaining to distinguish parenchymal microglia. At baseline, the AP contained abundant P2RY12-negative, Iba1-positive cells within the PVS, closely aligned to basement membranes and exceeding levels in other regions. We then induced type 1 diabetes with streptozotocin (200 mg/kg) and examined tissue 7 days later, comparing the AP with the BBB-intact solitary nucleus (Sol). In the AP, PVS area was significantly reduced, structural complexity increased, and Iba1-positive cell numbers rose; no comparable changes were detected in the Sol. These findings indicate that CVO PVS harbor a distinct Iba1-positive, P2RY12-negative immune niche. In the AP, vascular and immune compartments remodel within 1 week of systemic metabolic perturbation, nominating the AP as an early-responding hub for peripheral-to-brain signaling and a target for early biomarker development and intervention in diabetes, and early therapeutic targeting.

The autonomic nervous system (ANS) coordinates the body's response to stress. Proinflammatory cytokines [e.g., tumor necrosis factor-alpha (TNFα)], released in response to different stressors, may influence underlying pathophysiology involving autonomic dysfunction. The present study evaluated the impact of peripheral TNFα on cellular activation in brain stem nuclei associated with autonomic function, including the dorsal vagal complex (DVC) and the ventral lateral medulla (VLM). Mice received a single intraperitoneal injection of TNFα and were processed 2 h later to identify immunoreactive c-Fos in brain stem nuclei as a measure of cellular activity. The number of c-Fos-immunoreactive cells increased after TNFα challenge within the DVC and VLM. Cells immunoreactive for c-Fos were concentrated lateral to the area postrema (AP), a circumventricular organ medial to the subdivision of the caudal portion of the nucleus of the solitary tract (cNTS) within the DVC. To examine the role of microglia in mediating cellular responses to peripheral TNFα, minocycline was administered into the fourth ventricle to decrease microglial function. Minocycline treatment reduced ionized calcium binding adapter molecule 1 (IBA-1) immunoreactivity in the AP and cNTS. When animals were challenged with TNFα after receiving minocycline, fewer c-Fos-positive cells were induced in the DVC and selectively in the rostral VLM. These findings highlight the spatial selectivity of cells in the brain stem to increased peripheral proinflammatory signaling, as well as the impact of resident microglia on autonomic circuitry responses.NEW & NOTEWORTHY This study investigates how peripheral tumor necrosis factor-alpha (TNFα) affects neuronal activity in autonomic nuclei of the brain stem and how microglia contribute to this response. Peripheral TNFα increased neuronal activation (c-Fos expression) in the dorsal vagal complex (DVC) and ventrolateral medulla (VLM), particularly near the area postrema. Inhibiting microglia with intracerebroventricular minocycline reduced both microglial markers and TNFα-induced neuronal activity, suggesting that microglia play a key role in modulating cytokine-driven autonomic signaling in the brain stem.

Integrating clinical findings with neuroradiological changes is a crucial skill in neurology, particularly for diagnosis. Multiple Sclerosis (MS) lesions in the brainstem are rarely asymptomatic, leading to unique and often localised clinical syndromes. MS lesions exhibit a characteristic perivenular distribution, which in the brainstem is imprinted by the consistent topography of the penetrating veins. This review provides an integrative perspective on the anatomical patterns of MS lesions in the brainstem (midbrain, pons, and medulla). It correlates specific clinical syndromes with radiological appearances, aiding in both diagnosis and functional localisation. We searched the available literature using keywords related to the three brainstem sections (midbrain, pons, medulla) and eloquent anatomical locations (medial longitudinal fasciculus, cerebellar peduncle, nerve fascicle, aqueduct, area postrema), aiming to correlate specific radiological patterns of MS lesions with their consistent clinical syndromes as reported in the literature. Brainstem MS lesions often cause irritative symptoms rather than full functional loss. Unlike other conditions, visible MS lesions on MRI rarely disappear and usually remain as silent lesions following an acute event. The consistent venous architecture creates specific radiological patterns that link to distinct clinical presentations. In contrast, inflammatory disorders like NMOSD and MOGAD cause more aggressive and extensive dysfunction. The visual details of MS brainstem lesions reflect their close relationship to venous anatomy, which can be anticipated even when the central vein sign is not directly visualised. Recognising these specific clinical-radiological syndromes provides a unique and insightful diagnostic tool for MS, underscoring the value of strong functional and radiological-anatomical interpretation skills in clinical neurology.

Physical activity promotes gut adaptation, nutrient responsiveness, and sensitivity to gut peptides in male mice.

Background: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease with important disability accumulation. Early-onset NMOSD, defined as disease onset before age 50, exhibits distinct clinical characteristics compared to late-onset disease. We present a case series of patients with first symptom onset before age 30. Methods: A retrospective review of 10 patients diagnosed with NMOSD at our center in San Luis Potosí, Mexico, with disease onset before age 30. Clinical presentation, imaging findings, AQP4 antibody status, treatment response, and disability outcomes were analyzed. Results: The mean age at onset was 18.6 years (range 6–30). Area postrema syndrome was the most common presentation (40%), followed by acute myelitis and optic neuritis (30% each). All tested patients were AQP4-positive. The mean EDSS at follow-up was 6.6, indicating severe disability. Most patients received rituximab with variable response rates. Conclusions: Our cohort showed higher disability than reported in other early-onset series, emphasizing the need for prompt diagnosis and aggressive treatment in this population.

Autonomic reflexes, controlling unconscious processes such as heart rate and digestion, are essential for homeostasis. Vago-vagal reflexes describe one category of autonomic reflexes in which the sensory input and motor output are both mediated through the vagus nerve. These reflexes are widely considered to rely on the nucleus of the solitary tract (NTS) for the integration of sensory information before regulating the motor output from the dorsal motor nucleus of the vagus (DMV). Here, we electrically activated the solitary tract to evoke sensory input simultaneous to whole cell recordings of DMV neurones. Criteria around measures of synaptic jitter, amplitude variance and paired pulse ratio were used to identify that ∼7% of DMV neurones probably receive direct vagal sensory input. We utilised channelrhodopsin-assisted circuit mapping to definitively confirm sensory to motor synapses. In brain slices where vagal afferents could be activated selectively with optogenetics, we evoked postsynaptic events in some DMV neurones. In some of these, optogenetically evoked input persisted in the presence of tetrodotoxin. These results confirm monosynaptic connections between vagal afferent fibres and DMV motor neurones. This study challenges the canonical circuitry underlying vago-vagal reflexes, confirming some sensory vagal afferents synapse at some DMV motor neurones, bypassing the NTS, to drive parasympathetic motor output directly. KEY POINTS: Vagal afferents terminate at second order neurones in the solitary tract nucleus, paratrigeminal nucleus and area postrema. Neuroanatomical data suggests vagal sensory afferents may also terminate and synapse onto motor neurones within the dorsal motor nucleus of the vagus (DMV) to directly modulate parasympathetic output. We utilised traditional electrical activation and channelrhodopsin-assisted circuit mapping to definitively confirm that vagal sensory afferents synapse onto DMV motor neurones. These findings suggest that some vago-vagal reflexes may be mediated by a direct sensory vagus-to-DMV circuit, enabling precise and uninterrupted drive to increase parasympathetic output.

Survodutide is a novel GCG/GLP-1 receptor (GCGR/GLP-1R) dual agonist in clinical development for people with obesity and people with metabolic dysfunction-associated steatohepatitis (MASH). Preclinically, survodutide demonstrated body weight lowering efficacy through decreased energy intake and increased energy expenditure. Here, we investigated the central site of action of survodutide and provide further insights into its mechanism of action in reducing body weight. We assessed GCGR and GLP1R expression in human and mouse circumventricular organs (CVOS) and showed for the first time that GCGR is barely detectable in area postrema (AP) and arcuate nucleus of the hypothalamus (ARH) at the single cell level. In contrast, GLP1R is expressed in these tissues. Using a fluorophore labeled survodutide to visualize sites of action in the mouse brain, survodutide was observed to directly access the CVOs and adjacent hypothalamic and hindbrain nuclei, without evidence of uniformly crossing the blood-brain-barrier. In addition, c-Fos labeling showed that multiple nuclei associated with the control of food intake were activated by survodutide. Consistent with the hypothesis that the intake suppressive effects of survodutide are GLP-1R dependent, a long-acting GCGR agonist did not induce neuronal activation in satiety-mediating regions, nor reduced food intake but showed reduction in body weight. These data further support the dual mode of action of survodutide and its potential to provide clinical benefit for people with obesity and/or MASH.

Pediatric neuromyelitis optica spectrum disorders in Dakar: Insights from a preliminary multicentric case series in Senegal.

Characterizing double seronegative neuromyelitis optica spectrum disorder: A distinct subgroup or part of the continuum?

Introduction: Area postrema syndrome, characterized by nausea, emesis, and persistent hiccups can be initial manifestation of demyelinating diseases of the central nervous system. Clinical case: we report a 4-year-old girl who presented with intractable vomiting that was noted to have signs of demyelination in the area postrema. MRI spine revealed longitudinally extensive myelitis in the cervical and thoracic spine. Neuromyelitis optica spectrum disorder was suspected. Serum anti-aquaporin 4 antibodies were positive. Oligoclonal bands in cerebrospinal fluid were negative. Conclusion: Neuromyelitis optica spectrum disorders are extremely rare in the pediatric population, this being the second case reported in Colombia. . It’s crucial to consider the possibility of such neurological disorders in the setting of intractable vomiting.

Human chorionic gonadotropin inhibits locomotion but not food intake independently of the area postrema and the nucleus tractus solitarius in female mice.

Pancreatic amylin dynamically reconfigures distributed brain networks governing appetite regulation in mice

Comparative analysis of AQP4-IgG-positive and AQP4-IgG-negative NMOSD: A multicenter study in Latin America.

A case of episodic intractable hiccups from Area Postrema Syndrome: A rare manifestation of multiple sclerosis

The nucleus of the solitary tract (NTS) and the area postrema (AP) form a tightly coupled dorsal medullary complex that integrates visceral and humoral signals governing autonomic and cardiometabolic regulation. While their neural interconnections are well characterized, the organization and functional significance of their shared vascular network remain poorly understood. Here, we used in vivo two-photon microscopy in rats, combined with fluorescent vascular labeling and retrograde neuronal tracing, to visualize and quantify blood flow within the AP–NTS microcirculation. We identified direct capillary connections between the two regions, confirming a continuous vascular network previously inferred from ex vivo studies. Analysis of red blood cell trajectories revealed that blood flow across these junctions is predominantly unidirectional, from the NTS toward the AP. Morphometric measurements showed that AP capillaries are nearly twice the diameter of those in the NTS, implying a lower local vascular resistance and providing a structural basis for this directionality. Despite these geometric differences, capillary flow velocities were similar between regions, consistent with active regulation that maintains stable perfusion dynamics. Together, these findings uncover a previously unrecognized, functionally asymmetric vascular pathway within the dorsal medulla. By enabling the directed transfer of diffusible neurohumoral signals from the NTS to the AP, this specialized microvascular network adds a novel layer of communication between two key brainstem autonomic centers and may represent an additional mechanism for the integration of visceral and circulating information.

MCC950 attenuates thyroidectomy-induced retching-like behavior by inhibiting NLRP3-mediated IL-1β release.

This article summarizes the key literature describing the effects of the pancreatic beta-cell hormone amylin on eating. One of the first described and best investigated effects of amylin on eating is its physiological effect to control meal size by inducing satiation. This effect is very rapid, short-lasting and probably directly reflects the meal-induced increase in circulating amylin levels. Evidence provided by many groups suggests that the effect of amylin on eating is directly mediated by humoral action in the central nervous system rather than by peripheral receptors. It is also clear that the caudal hindbrain, in particular the area postrema, is a key brain region mediating amylin effects, but amylin may also act at different sites in the brain. The latter is particularly true for the effect of amylin to reduce food reward. Hence, amylin not only reduces caloric intake as such but may specifically reduce high fat intake, at least in certain experimental conditions; in people, amylin receptor agonists have been shown to reduce the number of binge eating episodes. In recent years, long-lasting amylin receptor agonists have been developed. Alone or in combination with other gut hormone receptor agonists (in particular the agonist of glucagon-like peptide-1 [GLP-1] receptor, semaglutide), these molecules turned out to be highly promising therapeutic agents for the treatment of obesity.

A comparative study on clinico-radiological profile, treatment responses and outcomes of double seronegative NMOSD compared to AQP4-IgG positive NMOSD, and MOGAD.

The presence of neural stem cells (NSCs) of the subventricular and subgranular zone in the adult mammalian brain has been the focus of much attention; however, these high-function centers have low regenerative ability in response to brain damage. In this review, we focus on the mediobasal hypothalamus (MBH)-a diencephalic region lining the floor of the third ventricle-and the medulla oblongata, a brainstem structure. Both contain niche-like glial populations with context-dependent neurogenic and gliogenic potential. These evolutionarily conserved regions contain neural circuits essential for life support and display high regenerative capacity in lower vertebrates. Recently, NSCs and neural progenitor cells (NPCs) have been reported in the MBH, including the arcuate nucleus and median eminence. Mediobasal hypothalamic tanycytes, with proximal cell bodies facing the third ventricle and distal cellular processes toward the parenchyma, are identified as NSCs that supply various progenitor and ependymal cells. Neural circuits of the MBH exhibit relatively regenerative capability with near-complete or alternative neuronal circuit reorganization after hypothalamic neuronal damage. In the medulla oblongata, there are two types of NSCs: astrocyte-like NSCs in the area postrema and tanycyte-like NSCs in the central canal facing the cerebrospinal fluid. Astrocyte-like NSCs exhibit relatively active proliferation, whereas tanycyte-like NSCs are almost quiescent. Monosodium glutamate selectively induces neuronal cell death in the area postrema, and NPCs proliferate and differentiate into mature neurons, resulting in near-complete restoration of neuronal density. Experimental autoimmune encephalomyelitis causes demyelination in the medulla oblongata, and NSCs partially restore the density of oligodendrocytes. Thus, recent studies indicate that the adult MBH and medulla oblongata exhibit context-dependent regenerative responses, supplying new neurons and oligodendrocytes in response to brain damage.