Gait Ignition Failure in JNPL3 Human Tau-mutant Mice

Cognitive impairments and motor dysfunction are commonly observed behavioral phenotypes in genetic animal models of neurodegenerative diseases. JNPL3 transgenic mice expressing human P301L-mutant tau display motor disturbances with age- and gene dose-dependent development of neurofibrillary tangles, suggesting that tau pathology causes neurodegeneration associated with motor behavioral abnormalities. Although gait ignition failure (GIF), a syndrome marked by difficulty in initiating locomotion, has been described in patients with certain forms of tauopathies, transgenic mouse models mirroring human GIF syndrome have yet to be reported. Using the open field and balance beam tests, here we discovered that JNPL3 homozygous mice exhibit a marked delay of movement initiation. The elevated plus maze excluded the possibility that hesitation to start in JNPL3 mice was caused by enhanced levels of anxiety. Considering the normal gait ignition in rTg4510 mice expressing the same mutant tau in the forebrain, GIF in JNPL3 mice seems to arise from abnormal tau deposition in the hindbrain areas involved in locomotor initiation. Accordingly, immunohistochemistry revealed highly phosphorylated paired helical filament tau in JNPL3 brainstem areas associated with gait initiation. Together, these findings demonstrate a novel behavioral phenotype of impaired gait initiation in JNPL3 mice and underscore the value of this mouse line as a tool to study the neural mechanisms and potential treatments for human GIF syndrome.

AcuD Gene Knockout Attenuates the Virulence of Talaromyces marneffei in a Zebrafish Model

Talaromyces marneffei is the only dimorphic species in its genus and causes a fatal systemic mycosis named talaromycosis. Our previous study indicated that knockdown of AcuD gene (encodes isocitrate lyase of glyoxylate bypass) of T. marneffei by RNA interference approach attenuated the virulence of T. marneffei, while the virulence of the AcuD knockout strains was not studied. In this study, T. marneffei-zebrafish infection model was successfully established through hindbrain microinjection with different amounts of T. marneffei yeast cells. After co-incubated at 28°C, the increasing T. marneffei inoculum doses result in greater larval mortality; and hyphae generation might be one virulence factor involved in T. marneffei-zebrafish infection. Moreover, the results demonstrated that the virulence of the ΔAcuD was significantly attenuated in this Zebrafish infection model.

Hidrocefalia Congénita: Síndrome de Gómez-López-Hernández, un síndrome subdiagnosticado. Caso clínico / Congenital Hydrocephalus: Gómez-López-Hernández syndrome. An underdiagnosed Syndrome. A clinical case

Resumen: Introducción: Las hidrocefalias son condiciones complejas influenciadas por factores genéticos y ambientales. Excluyendo las hidrocefalias adquiridas por infección o tumores encefálicos, las hidrocefalias congénitas de causa genética pueden ocurrir de forma aislada (hidrocefalia aislada, pura o no sindromática) o como componente de un síndrome genético definido (hidrocefalia sindromática). Objetivo: Presentar una hidrocefalia congénita sindromática con un diagnóstico co nocido, y realizar una revisión de la literatura. Caso clínico: Preescolar con diagnóstico prenatal de hidrocefalia y romboencefalosinapsis, cariotipo y estudio de TORCH normales. Al nacer se confirmaron los diagnósticos prenatales y se excluyó malformación del desarrollo cortical cerebral. En la primera semana de vida se realizó derivación ventrículo peritoneal. En una reevaluación a la edad de 4 años, la ausencia de reflejos corneales y alopecia parietal bilateral asociado a romboencefalosinapsis reunieron los criterios diagnósticos definitivos de una displasia cerebelo-trigémino dermal (Síndrome de Gómez, López-Hernández (SGLH)). Conclusiones: El SGLH es un síndro me neurocutáneo infrecuente, posiblemente una condición esporádica que está subdiagnostica da. Con las nuevas tecnologías imageneológicas y genéticas pre y post natales podemos acceder a un diagnóstico de precisión de las hidrocefalias de origen genético, en el cual la alta sospecha de equipos de especialistas clínicos es esencial. Sin el diagnóstico preciso no podemos acceder a un pronóstico a largo plazo, prevención de morbilidad agregada y un consejo genético adecuado, que son requeridos en la pediatría actual.

Abstract: Introduction: Hydrocephalus is defined as complex conditions influenced by genetic and environmental factors. Excluding hydrocephalus acquired from infection or brain tumors, congenital hydrocephalus with a genetic cause may occur isolated (hydrocephalus isolated, pure or non-syndromatic) or as a component of a genetic syndrome (syndromic hydrocephalus). Objective: To present a syndromic congenital hydrocephalus with a known diagnosis, in order to be considered in the study of this pathology and to perform a review of hydrocephaly with a genetic cause. Clinical case: Preschool with a prenatal diagnosis of hydrocephalus and rhombencephalosynapsis, karyotype and study of TORCH was normal. At the moment of birth, the prenatal diagnoses were confirmed and a malformation of cerebral cortical development was excluded. During the first week of life, perito neal ventricle shunt was performed. A reevaluation at age 4, the absence of corneal reflexes bilate ral parietal and congenital focal alopecia associated with rhombencephalosynapsis, meet definitive criteria for cerebello-trigeminal-dermal displasia or Gómez-López-Hernández syndrome (GLHS). Conclusions: GLHS is an uncommon neurocutaneous syndrome, possibly a sporadic condition that is underdiagnosed. Due to the new imaging and genetic technologies pre and post-natal, today it is possible to achieve a better and more accurate diagnosis of hydrocephalus with a genetic origin, in which the high suspicion of teams of clinical specialists is essential. Without accurate diagnosis, we can not access to a long-term prognosis, prevention of aggregate morbidity or an adequate genetic counseling, which are required in today's pediatrics.

Rebound Feeding in the Wake of Short-Term Suspension of Food Intake Differs in the Presence of Estrous Cycle Peak versus Nadir Levels of Estradiol

BACKGROUND: Short-term interruption of feeding is ordinary in modern life but negatively impacts appetite control and body weight. Estradiol (E) imposes long-term inhibitory tonus on food consumption; however, E influence on energy repletion secondary to food deprivation (FD) is unclear. This study investigated the hypothesis that E signal strength regulates hyperphagic responses to FD of varying duration. METHODS: Ovariectomized female rats were implanted with E-containing silastic capsules (30 [E-30] or 300 µg [E-300]/mL) to replicate plasma concentrations at cycle nadir versus peak levels. RESULTS: Data show that food intake was increased equally in E-30 and E-300 rats after 12 hours of food deprivation (FD-12); yet, FD of 18 hours (FD-18) amplified refeeding by E-300 versus E-30. Caudal fourth ventricular administration of the 5′-monophosphate-activated protein kinase (AMPK) inhibitor compound C (Cc) did not modify FD-induced hyperphagia in E-30 (regardless of FD interval) or E-300 animals exposed to FD-12, but diminished refeeding after FD-18 in E-300 rats. Cc-reversible hyperglycemia occurred in refed FD-18 groups. Serum insulin was resistant to FD-12 plus refeeding, but was elevated by AMPK-dependent mechanisms in refed E-300 FD-18 rats; equivalent Cc-insensitive decrements in circulating leptin occurred in all FD groups. CONCLUSION: Current results show that estrous cycle peak, but not baseline, E levels engage hindbrain AMPK signaling to intensify hyperphagia in response to prolongation of FD. Observations of hindbrain AMPK-dependent hyperglycemia, alongside elevated insulin secretion, in refed rats exposed to FD-18 implicate this sensor in insulin resistance mechanisms of glucose partitioning in response to this metabolic imbalance.

Joubert Syndrome Presenting With Normal Pyramidal Decussation: A Case Report

Joubert syndrome (JS) is a rare genetic disorder characterized by a congenital malformation of the hindbrain, and accompanied by axonal decussation abnormalities affecting the corticospinal tract and the superior cerebellar peduncles. To the best of our knowledge, there are no reports of normal pyramidal decussation in JS. Here, we describe the case of an 18-year-old boy presenting midline-crossing corticospinal projections, which were considered normal corticospinal tract trajectories. Diffusion tensor imaging and motor evoked potential study analysis demonstrated the exclusive presence of decussating corticospinal projections in the patient. Based on these results, we suggest that JS might be associated with several, diverse corticospinal motor tract organization patterns.

Type I Chiari malformation presenting orthostatic syncope who treated with decompressive surgery / 소아과

Chiari malformations are a congenital anomaly of the hindbrain. The most common, Chiari malformation type I (CM-I), is characterized by herniation of the cerebellar tonsils extending at least 3 mm below the plane of the foramen magnum. Consequently, CM-I is associated with hydrocephalus and symptoms involving compression of the cervicomedullary junction by ectopic tonsils. Several studies have reported the clinical symptoms associated with CM-I, including suboccipital headache, weakness in the upper extremities, facial numbness, loss of temperature sensation, ataxia, diplopia, dysarthria, dysphagia, vomiting, vertigo, nystagmus, and tinnitus. Syncope is one of the rarest presentations in patients with CM-I. There are many hypotheses regarding the causes of syncope in patients with CM-I; however, the mechanisms are not clearly understood. Although surgical decompression for CM-I in patients with syncope has yielded good clinical results in some studies, such cases are rarely reported. We report a case of orthostatic syncope in a patient with CM-I who was treated with surgical intervention.

A Wide Spectrum of Axial Mesodermal Dysplasia Complex With Rhombencephalic Anomaly: A Case Report

Axial mesodermal dysplasia complex (AMDC) arises in variable combinations of craniocaudal anomalies such as musculoskeletal deformities, neuroschisis, or rhombencephalic developmental disorders. To the best of our knowledge, the co-existence of AMDC with associated musculoskeletal anomalies, medullary neuroschisis with mirror movements, and cranial nerve anomalies has not yet been reported. Here, we report the case of a 4-year-old boy whose clinical features were suggestive of Goldenhar syndrome and Poland syndrome with Sprengel deformity. Moreover, he showed mirror movements in his hands suspected of rhombencephalic malformation, and infranuclear-type facial nerve palsy of the left side of his face, the opposite side to the facial anomalies of Goldenhar syndrome. After conducting radiological studies, he was diagnosed with medullary neuroschisis without pontine malformations and Klippel-Feil syndrome with rib anomalies. Based on these findings, we propose that clinical AMDC can be accompanied by a wide variety of musculoskeletal defects and variable degrees of central nervous system malformations. Therefore, in addition to detailed physical and neurological examinations, imaging studies should be considered in AMDC.

Surgical Outcome of Adult Idiopathic Chiari Malformation Type 1

OBJECTIVE: The pathophysiology of idiopathic Chiari malformation (CM) type 1 is disturbance of free cerebrospinal fluid (CSF) flow and restoration of normal CSF flow is the mainstay of treatment. Additional migration of the medulla oblongata in pediatric patients is referred to as CM type 1.5, but its significance in adult patients is unknown. This study is to compare surgical outcomes of adult idiopathic CM type 1.5 with that of type 1. METHODS: Thirty-eight consecutive adult patients (M : F=11 : 27; median, 33.5; range, 18–63) with syringomyelia due to idiopathic CM type 1 were reviewed. Migration of the medulla oblongata was noted in 13 patients. The modified McCormick scale (MMS) was used to evaluate functional status before and one year after surgery. All patients underwent foramen magnum decompression and duroplasty. Factors related to radiological success (≥50% decrease in the diameter of the syrinx) were investigated. The follow-up period was 72.7±55.6 months. RESULTS: Preoperative functional status were MMS I in 11 patients and MMS II in 14 of CM type 1 and MMS I in 8 and II in 5 of CM type 1.5. Of patients with MMS II, 5/14 patients in group A and 3/5 patients in group B showed improvement and there was no case of deterioration. Radiological success was achieved in 32 (84%) patients and restoration of the cisterna magna (p=0.01; OR, 46.5) was the only significant factor. CONCLUSION: Migration of the medulla oblongata did not make a difference in the surgical outcome when the cisterna magna was restored.

Comparison of teratogenecity induced by nano- and micro-sized particles of zinc oxide in cultured mouse embryos / 대한수의학회지

The increasing uses of zinc oxide nanoparticles (nZnO) in industrial and personal care products raise possible danger of using nZnO in human. To determine whether ZnO induces size-dependent anomalies during embryonic organogenesis, mouse embryos on embryonic day 8.5 were cultured for 2 days under 50, 100, and 150 microg of nZnO (< 100 nm) or micro-sized ZnO (mZnO; 80 +/- 25 microm), after which the morphological changes, cumulative quantity of Zn particles, and expressions of antioxidant and apoptotic genes were investigated. Although embryos exposed to 50 microg of ZnO exhibited no defects on organogenesis, embryos exposed to over 100 microg of ZnO showed increasing anomalies. Embryos treated with 150 microg of nZnO revealed significant changes in Zn absorption level and morphological parameters including yolk sac diameter, head length, flexion, hindbrain, forebrain, branchial bars, maxillary process, mandibular process, forelimb, and total score compared to the same dose of mZnO-treated embryos. Furthermore, CuZn-superoxide dismutase, cytoplasmic glutathione peroxidase (GPx) and phospholipid hydroperoxidase GPx mRNA levels were significantly decreased, but caspase-3 mRNA level was greatly increased in nZnO-treated embryos as compared to normal control embryos. These findings indicate that nZnO has severer teratogenic effects than mZnO in developing embryos.

Acute Disseminated Encephalomyelitis Presenting as Rhombencephalitis: An Atypical Case Presentation

Acute disseminated encephalomyelitis (ADEM) is a demyelinating and inflammatory condition of the central nervous system, occurring predominantly in white matter. ADEM involving the rhombencephalon without affecting the white matter is very rare. Here, we present an unusual case of ADEM involving only the rhombencephalon in a 4-year-old Asian girl. The patient complained of pain in the right lower extremities, general weakness, ataxia, and dysarthria. The initial brain CT showed subtle ill-defined low-density lesions in the pons and medulla. On brain MRI, T2 high signal intensity (T2-HSI) lesions with mild swelling were present in the pons, both middle cerebellar peduncles, and the anterior medulla. The initial diagnosis was viral encephalitis involving the rhombencephalon. Curiously, a cerebrospinal fluid (CSF) study revealed no cellularity, and negative viral marker findings. Three weeks later, follow up brain MRI showed that the extent of the T2-HSI lesions in the brain stem had decreased. After reinvestigation, it was found that she had a prior history of upper respiratory infection. In this case, we report the very rare case of a patient showing isolated involvement of the rhombencephalon in ADEM, mimicking viral rhombencephalitis on CT and MR imaging. ADEM can involve unusual sites such as the rhombencephalon in isolation, without involvement of the white matter or deep gray matter and, therefore, should be considered even when it appears in unusual anatomical areas. Thorough history taking is important for making a correct diagnosis.

Leptin receptor of the hind brain nuclei is involved in the conditioned taste preference of rats / 中国应用生理学杂志

<p><b>OBJECTIVE</b>Conditioned taste preference (CTP) is a taste learning reflex by which an animal learns to prefer a substance which tastes not well and has been studied with much interest in recent years. However, the neural substrates of CTP are less known. This study aimed to determine the possible neural path- ways of CTP and whether serum leptin level and the leptin receptor (OB-Rb) in the hind brain are involved following CTP formation.</p><p><b>METHODS</b>We established CTP of quinine in rats with a 2-bottle preference test. The serum leptin concentrations were detected, the expression of c-fos in the rat brain was tested to determine the nuclei in relation with establishment of CTR Finally, the OB-Rb mRNA expression was examined by RT-qPCR assay in parabrachial nucleus (PBN) and the nucleus of the solitary tract (NST) of the hind brain.</p><p><b>RESULTS</b>Compared with control group, the level of serum leptin was higher in the CTP group (4.58 ± 0.52 vs 1.67 ± 0.25 µg/L, P < 0.01); increased c-fos positive cells were found in the anterior hypothalamus (AH, 221.75 ± 4.96 vs. 178.50 ± 6.63 cells/mm², P < 0.05), the basal lateral amygdala (BLA, 70.75 ± 6.17 vs 56.50 ± 3.62 cells/ mm², P < 0.05) and the nucleus of the solitary tract (NST, 41.25 ± 1.32 vs 32.50 ± 1.02 cells/mm², P < 0.05). But in ventromedial nucleus of the hypothalamus (VMH, 20.75 ± 2.73 vs 38.5 ± 1.54 per 1 mm², P < 005), PBN (21.50 ± 2.24 vs 36.25 ± 1.49 cells/mm², P < 0.05) and the central nucleus of the amygdala (CeA, 22.25 ± 1.53 vs 35.50 ± 2.11 cells/mm², P < 0.05), the number of c-fos positive cells was decreased in the CTP group. In addition, we found OB-Rb mRNA expression in PBN of CTP group rats was higher than that of control group (0.95 ± 0.055 vs 0.57 ± 0.034, P < 0.05), while there was no significant difference of OB-Rb mRNA expression in NST between the two groups.</p><p><b>CONCLUSION</b>Nuclei AH, BLA, NST, VMH, PBN and CeA participate in the formation of CTP. Leptin and its receptor in PBN may be involved in the formation and maintenance of CTP.</p>

Aneurysm of the Posterior Meningeal Artery Embedded Within a Dorsal Exophytic Medullary Hemangioblastoma: Surgical Management and Review of Literature

Hemangioblastomas are World Health Organization (WHO) Grade I neoplasms of the hindbrain and spinal cord, whose management can be complicated by preoperative hemorrhage. We report on a case of a young female in extremis with posterior fossa hemorrhage following rupture of a fusiform posterior meningeal artery aneurysm embedded within a medullary hemangioblastoma. We discuss management options, including operative staging and embolization, and review similar cases of hemangioblastoma associated with aneurysm.

Expression and antioxidation of Nrf2/ARE pathway in traumatic brain injury

OBJECTIVE@#To explore the expression of Nrf2/ARE pathway in hindbrain tissue after the traumatic brain injury (TBI) and its anti-oxidative stress effect in the secondary nerve injury.@*METHODS@#The mice with Nrf2 gene knockout were used for the establishment of brain injury model. The experimental animals were divided into four groups: (Nrf2(+)/(+)) sham-operation group, (Nrf2(+)/(+)) brain injury group, (Nrf2(-)/(-)) sham-operation group and (Nrf2(-)/(-)) brain injury group. The specimen 24 h after cerebral trauma was selected. Then RT-PCR method was adopted to detect the expression of Nrf2 mRNA in brain; Western blotting method was adopted to detect the levels of Nrf2, HO-1 and NQO1 proteins in brain; ELISA method was adopted to detect the oxidative stress indicators: protein carbonyls, 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-2'-deoxyguanosine (8-OHdG).@*RESULTS@#The Nrf2 mRNA and protein of Nrf2(-)/(-) mice were not expressed, and the difference of the relative amount of Nrf2 mRNA between Nrf2(+)/(+) TBI group and Nrf2(+)/(+) sham-operation group was not statistically significant (P>0.05); the level of Nrf2 protein in Nrf2(+)/(+) TBI group increased significantly compared with the Nrf2(+)/(+) sham-operation group (P0.05); there was only a little amount of expression of protein carbonyls, 4-HNE and 8-OHdG proteins in brain tissues in the Nrf2(+)/(+) and Nrf2(-)/(-) sham-operation groups, and the difference was not statistically significant (P>0.05); after brain injury, the three oxidative stress indicators were significantly up-regulated in the Nrf2(+)/(+) and Nrf2(-)/(-) groups, and the up-regulation of the latter group was more significant (P<0.01).@*CONCLUSIONS@#After TBI the Nrf2/ARE pathway is activated and the activity of Nrf2 transcription regulation increases. However, the regulation dose not occur in the gene transcription level and only could increase the Nrf2 protein level, while the mRNA expression level has no obvious change. The nerve cell protective effect of Nrf2/ARE pathway in TBI achieves through inhibiting the oxidative stress injuries.

A Case of Rhombencephalitis Presented with Intractable Hiccup

The term 'rhombencephalitis' refers to inflammatory diseases affecting the hindbrain. We experienced a case of rhombencephalitis in a 14 years old girl, who presented with fever, headache, and intractable hiccup for one week prior to admission. Brain MRI on admission showed bilateral high signal intensities in the dorsal portion of the medulla oblongata on T2WI and FLAIR. Examination of cerebrospinal fluid showed increased WBC count (33/mm3, Lymphocyte 81%), normal protein and glucose level. Immunoserologic study showed decreased C3, C4 level and increased Anti-ds DNA level. However, FANA was negative. The hiccup was controlled by administration of IVIG (1 g/kg/day for 2 days) and steroid (30 mg/kg/day for 3days) without any neurologic symptoms. We report a case with the brief review of related literatures.

Romboencefalitis por Listeria monocytogenes: Patología emergente en relación al brote epidémico. Presentación de tres casos clínicos / Listeria monocytogenes rhomboencephalitis: Report of three cases

An unusual number of cases of rhomb encephalitis have occurred in Chile because of the increased frequency of infections caused by Listeria monocytogenes. We report three females aged 36, 40 and 55 years, with the disease. All presented with a prodrome characterized by headache, nausea, vomiting and fever, followed by ataxia and unilateral palsies of the third, seventh and twelfth cranial nerves. One patient presented also a hemi-hypoesthesia. Magnetic resonance showed lesions in the posterior aspect of the brain stem, specifically in relation to the floor of the fourth ventricle. Blood cultures were positive for Listeria monocytogenes.

Rhombencephalosynapsis: association with single umbilical artery.

A 6-year-old girl who presented with developmental delay and non-progressive ataxia is described. MRI of brain showed agenesis of cerebellar vermis with fusion of cerebellar hemispheres and dentate nuclei. MRI findings were characteristic of rhombencephalosynapsis. Partial agenesis of corpus callosum and absent septum pellucidum were also seen. The child had also been noted to have a single umbilical artery at birth: a hitherto undescribed association.

Effects of Chronic Alcohol Exposure on Dopaminergic and Serotonergic Neurotransmission System in Rat / 대한정신약물학회지

OBJECTIVE: This study investigates the effects of chronic alcohol exposure on rat brain THmRNA expression, TH (tyrosine hydroxylase) acitivity, and TPH (tryptophan hydroxylase) activity which are important in synthesis of dopamine and serotonin and other components of both the dopaminergic and serotonergic systems of the rat brain. METHODS: Rats were fed a liquid diet containing alcohol for 4 weeks. We investigated effects of chronic alcohol exposure on dopaminergic systems as follows. We evaluated expression of THmRNA in LC, VTA and substantia nigra by using in-situ hybridization and measured activity of TH by using immunoassay. We used HPLC for simultaneous measurement of dopamine, DOPAC and HVA in the cerebral cortex, striatum, hypothalamus, hippocampus, mid brain, hind brain, and cerebellum. Also we investigated serotonergic systems as follows. We evaluated expression of TH mRNA in the dorsal raphe nucleus by using radioprobe and measured the activity of TPH by using enzyme immunoassay. We used HPLC for simultaneous measurement of 5-HT and 5-HIAA in the cerebral cortex, striatum, hypothalamus, hippocampus, mid brain, hind brain, and cerebellum. RESULTS: Alcohol exposure for 4 weeks increased the expression of TH mRNA in the ventral tegmental area and the locus ceruleus but not in the substantia nigra. The 4 weeks of alcohol exposure did not cause significant changes in levels of dopamine and metabolites in the different areas of the brain, nor was it associated with changes in the maximal binding and affinity (Kd) of anterior striatal dopamine D2 receptor. Alcohol exposure for 4 weeks had no effect on the expression of TPH mRNA or on the activity of TPH in the dorsal raphe nucleus and the hypothalamus. CONCLUSION: We reported at first that chronic alcohol exposure could increase TH mRNA in the locus ceruleus. In a previous study of acute alcohol treatment, there is increase of dopamine metabolism but in this study, we did not observe any changes in dopamine metabolism in the different areas of the brain. Also we did not see any significant changes in the synthesis and metabolism of serotonin after 4 weeks of chronic alcohol exposure compared with control. Therefore, synthesis and metabolism of serotonin was affected in the acute phase. And, as previous reports have suggested, any changes caused by alcohol returned to previous levels via adaptation and regulatory mechanisms.

Understanding Stress by Neuroscience

Stress can be defined generally as reponses to stressors on the body or in a definition more focused on the central nervous system, it can be defined as alterations in neuro-psychological homeostatic processes. There is a psychological aspect to stress, related to issues such as memory, emotion, arousal, and also a biological aspect which included activation of specific brain and endocrine circuits. This article reviews a series of neurobiological mechanisms aimed at understanding what are pathways by which stress is perceived, processed, and transduced into a neuroendocrine response. Multiple brain structures are involved in the organization of responses to stressful stimuli. Among them the hypothalamus, septohippocampal structures, amygdala, cingulate and prefrontal cortices, hindbrain regions such as the brainstem catecholamine cell body group (A2/C2 cell groups in the nucleus of the tractus solitaris; A1/C1 cell groups in the ventrolateral medulla; A6 cell groups in the locus ceruleus), the parabrachial nucleus, cuneiform nucleus, and dorsal raphe nucleus are prominent structures. We reviewed with the focus on the classic stress circuits: the limbic- hypothalamic-pituitary- adrenal axis (LHPA) and locus ceruleus-norepinephrine (LC-NE) system. Our review indicates that the LHPA stress circuit and LC- NE system are the complex systems with multiple control mechanisms and that these mechanisms are altered in pathological states, such as chronic stress and depression. The holistic features described in this reviews can provide insight into the nature and location of brain circuits and neurotransmitter receptors involved in stress and the treatment of stress-related disorders.