A pontine-medullary loop crucial for REM sleep and its deficit in Parkinson's disease.

Identifying the properties of the rapid eye movement (REM) sleep circuitry and its relation to diseases has been challenging due to the neuronal heterogeneity of the brainstem. Here, we show in mice that neurons in the pontine sublaterodorsal tegmentum (SubLDT) that express corticotropin-releasing hormone-binding protein (Crhbp+ neurons) and project to the medulla promote REM sleep. Within the medullary area receiving projections from Crhbp+ neurons, neurons expressing nitric oxide synthase 1 (Nos1+ neurons) project to the SubLDT and promote REM sleep, suggesting a positively interacting loop between the pons and the medulla operating as a core REM sleep circuit. Nos1+ neurons also project to areas that control wide forebrain activity. Ablating Crhbp+ neurons reduces sleep and impairs REM sleep atonia. In Parkinson's disease patients with REM sleep behavior disorders, CRHBP-immunoreactive neurons are largely reduced and contain pathologic α-synuclein, providing insight into the mechanisms underlying the sleep deficits characterizing this disease.

[Aortic Valve Papillary Fibroelastoma Stated for Preoperative Twelve Years without Any Symptom: Report of a Case].

We experienced a case of papillary fibroelastoma of aortic valve, which had been located for preoperative 12 years without any symptom. We could assess tumor growth rate of 0.17 mm/year. Because of recent reports of recurrence, close follow-up should be continued.

Effectiveness of radiation therapy on brain invasion by human papillomavirus-related multiphenotypic sinonasal carcinoma: A case report.

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is newly suggested and characterized by HPV-related tumors. HMSC has a relatively good prognosis. No cases of brain invasion have been reported to date. We encountered a case of brain invasion by HMSC, in which we assessed the effectiveness of radiotherapy in comparison with biopsy and autopsy. A 69-year-old man was referred to a hospital three months after intracerebral hemorrhage (ICH). Contrast magnetic resonance imaging revealed a tumor in the ethmoid sinus involving the brain. We performed transnasal biopsy and intensity-modulated radiotherapy for sinonasal and intracranial lesions. Despite radiotherapy, the patient died on day 41 after radiation. Biopsy specimens displayed mixed findings of epithelial and mesenchymal components. The tumor was immunoreactive for p16, and the RNA in situ hybridization for HPV was positive. Finally, we diagnosed the patient as having HMSC. Autopsy of the sinonasal tissue revealed a reduction in the number of tumor cells. There was a marked reduction in the number of tumor cells in the sinonasal tissue compared to that in the invaded brain tissue. The effectiveness of radiotherapy could depend on the histopathological components and location of the lesion, even in the same patient.

Experience using mTOR inhibitors for subependymal giant cell astrocytoma in tuberous sclerosis complex at a single facility.

BACKGROUND: Subependymal giant cell astrocytoma (SEGA) is occasionally seen in tuberous sclerosis complex (TSC). Two main options are currently available for treating SEGA: surgical resection or pharmacotherapy using mammalian target of rapamycin inhibitors (mTORi). We hypothesized that opportunities for surgical resection of SEGA would have reduced with the advent of mTORi. METHODS: We retrospectively reviewed the charts of patients treated between August 1979 and July 2020, divided into a pre-mTORi era group (Pre-group) of patients treated before November 2012, and a post-mTORi era group (Post-group) comprising patients treated from November 2012, when mTORi became available in Japan for SEGA. We compared groups in terms of treatment with surgery or mTORi. We also reviewed SEGA size, rate of acute hydrocephalus, recurrence of SEGA, malignant transformation and adverse effects of mTORi. RESULTS: In total, 120 patients with TSC visited our facility, including 24 patients with SEGA. Surgical resection was significantly more frequent in the Pre-group (6 of 7 patients, 86 %) than in the Post-group (2 of 17 patients, 12 %; p = 0.001). Acute hydrocephalus was seen in 1 patient (4 %), and no patients showed malignant transformation of SEGA. The group treated using mTORi showed significantly smaller SEGA compared with the group treated under a wait-and-see policy (p = 0.012). Adverse effects of pharmacotherapy were identified in seven (64 %; 6 oral ulcers, 1 irregular menstruation) of the 11 patients receiving mTORi. CONCLUSIONS: The Post-group underwent surgery significantly less often than the Pre-group. Since the treatment option to use mTORi in the treatment of SEGA in TSC became available, opportunities for surgical resection have decreased in our facility.

Posttraumatic epilepsy may be a state in which underlying epileptogenicity involves focal cortical dysplasia.

INTRODUCTION: The occurrence rate of posttrauma epilepsy ranges widely from 1% to 30%. Little is known about the underlying epileptogenesis of traumatic brain injury (TBI)-related epilepsy (TRE), because no comparison between TRE and TBI without epilepsy has been performed in terms of neuropathology. Therefore, we postulated that different neuropathological factors may be present between TRE and TBI without epilepsy. The purpose of this study was to clarify differences between TRE and TBI without epilepsy. METHODS: We studied patients who experienced severe head trauma and underwent brain surgery. The age range of the patients was 9-71 years old. Patients with medically resistant epilepsy were included in the Epilepsy group, and patients without epilepsy were included in the nonepilepsy group. Pathological findings, age, sex, and cause of head trauma were statistically compared between these two groups. RESULTS: This study involved 10 patients, nine of whom met the inclusion criteria. Pathological findings for all patients in the Epilepsy group included focal cortical dysplasia (FCD) (p = 0.012). CONCLUSION: The difference between TRE and TBI without epilepsy was underlying FCD in patients with TRE.

A case of focal cortical dysplasia type Ib atypically showing reversible intensity changes on magnetic resonance imaging which could be affected by epileptic discharge activity.

Focal cortical dysplasia (FCD) was first described as a distinct neuropathological entity in 1971 by Taylor and colleagues. FCD is thought to be an embryological migration disorder and is thus considered a non-progressive, unchangeable disease throughout life. A 9-year-old right-handed boy was referred from a local hospital for medically intractable epileptic seizures. Serial magnetic resonance images (MRI) showed intensity changes that indicated exacerbation and remission. After presurgical evaluations including intracranial video-electroencephalogram monitoring, we performed a lesionectomy aided by MRI and epileptic focus resection. He has been free from seizures for more than 3 years. Neuropathological findings showed FCD type Ib. We surgically treated a patient with FCD, which showed MRI intensity changes indicating exacerbation and remission. Although FCD type Ib is generally invisible on MRI, in this patient, changes in intensity on MRI made FCD type Ib visible.

Mesenteric inflammatory veno-occlusive disease occurring during the course of ulcerative colitis: a case report.

BACKGROUND: Mesenteric inflammatory veno-occlusive disease (MIVOD) is difficult to diagnose because of its rarity, nonspecific clinical findings, and frequent confusion with other diseases including inflammatory bowel disease. This report presents a very rare case of MIVOD that occurred during the course of ulcerative colitis (UC). CASE PRESENTATION: A 32-year-old man, who had been diagnosed with UC at the age of 29 and was in remission maintained by oral administration of 5-aminosalicylic acid (5-ASA), showed exacerbation of diarrhea and was admitted to the hospital. Since it was deemed an exacerbation of UC, intravenous steroid therapy and oral administration of tacrolimus were initiated, but his condition continued to worsen. Abdominal computed tomography (CT) was performed and showed intraperitoneal free air, leading to a diagnosis of gastrointestinal perforation and the performance of emergency surgery (subtotal colectomy and ileostomy). Histopathological examination of the resected colon of the patient showed mucosal inflammatory findings that were not typical of UC, including multiple organized thrombi with recanalization in the veins existing in the submucosal layer to the subserosal layer and an increased infiltration of inflammatory cells. These findings led to the pathological diagnosis of MIVOD. CONCLUSION: We report a very rare case in which MIVOD occurred during the course of UC.

Cytomegalovirus initiates infection selectively from high-level ß1 integrin-expressing cells in the brain.

Cytomegalovirus (CMV) is a prevalent pathogen in intrauterine infections that causes congenital anomalies such as CMV encephalitis, which is characterized by the focal areas of reactive gliosis, reactive mononuclear cells, microglial nodules, and ventriculoencephalitis. To elucidate the mechanisms of CMV susceptibility in the developing brain, cell tropism and the infectious dynamics of CMV infection were investigated. We evaluated intraventricular and intravascular infections from the perspective of the distribution of CMV and its receptor (ß1 integrin) in the earliest phase of infection. Murine CMV (MCMV) immediate early 1-positive cells were colocalized mainly with meninges and choroid plexus (after intraventricular infection) or with endothelial cells and pericytes (after intravascular infection). Using green fluorescent protein-expressing recombinant MCMV particles and fluorescent microbeads (100 to 300 nm), we revealed that CMV particle size is the primary factor determining the initial CMV distribution. ß1 Integrin inhibition using a shRNA and functional blocking antibody significantly reduced MCMV infection. IHC analysis, flow cytometric, and brain slice analyses strongly support that high-level ß1 integrin-expressing cells (eg, endothelial cells, pericytes, meninges, choroid plexus, and neural stem progenitor cells) are the first targets of MCMV. Therefore, our data demonstrate that the initial distributions of MCMV particles and ß1 integrin determine the distinct pattern of infection in the brain in the acute phase.

[A Case of Poorly Differentiated Adenocarcinoma of the Colon with Rapid Postoperative Progression Suggestive of Peritoneal Dissemination].

A 62-year-old man was admitted to our hospital because of pain in the right lower abdomen and was diagnosed with cecal cancer and an associated abscess. The patient subsequently underwent right hemicolectomy. Histopathological examination was positive for por1, se, bd3, ly3, v0, PM0, and DM0. He was discharged from the hospital 21 days postoperatively. He was hospitalized with bloating of the right lower abdomen and inflammation 31 days postoperatively. He was later diagnosed with recurrence of the initial abscess, but his symptoms did not improve, and he was considered to have peritoneal dissemination. His general condition deteriorated rapidly, and he died approximately 1.5 months postoperatively. Histopathological and anatomical examination later confirmed multiple organ failure with peritoneal dissemination. It is reported that prognosis of poorly differentiated adenocarcinoma is worse than that for well- or moderately differentiated adenocarcinoma. Poorly differentiated adenocarcinoma may recur immediately after curative surgery.

Induction of murine TNBS colitis is strictly controlled by a modified method using continuous inhalation anesthesia with sevoflurane.

BACKGROUND: Trinitrobenzenesulfonic acid (TNBS)-induced colitis is one of the most widely used experimental colitis models. However, there is no standard procedure for inducing colitis by TNBS because it is difficult to achieve a uniform distribution of colitis. We have developed a modified method of murine TNBS-induced colitis that involves inhalation anesthesia with sevoflurane combined with both single and repeated TNBS administrations. AIMS: To compare the usefulness of our newly developed method for inducing murine TNBS-induced colitis with that of conventional intraperitoneal anesthesia. METHODS: TNBS in ethanol was administered to C57BL/6J mice held in an inverted vertical position either under continuous inhalation anesthesia with sevoflurane, in accordance with our newly developed method, or by intraperitoneal injection with 2.5 % avertin, in accordance with the conventional procedure. Body weight change, cytokine profile, and histological findings were examined during the course of colitis. RESULTS: The dispersion of anesthesia time, TNBS retention time, and nadir weight during the course of colitis was decreased using the newly developed method compared with the conventional procedure. Optimization of the modified TNBS-induced colitis, as evidenced by the predominant expression of Th1 and Th17 cytokines on day 7, was attained by the injection of 2.25 mg TNBS in 55 % ethanol. Regulation of the TNBS retention time using inhalation anesthesia with sevoflurane allowed strict control of the disease severity of TNBS-induced colitis. Using the modified method we were also able to develop a chronic TNBS-induced colitis model by repeated TNBS administration without excessive mortality of the mice. CONCLUSIONS: Our modified method for murine TNBS-induced colitis using continuous inhalation anesthesia with sevoflurane provides a better experimental colitis model following both single and repeated TNBS administrations.

Goblet Cell Adenocarcinoma in the Stomach: A Case Report.

Goblet cell adenocarcinoma (GCA) is known as an amphicrine tumor often seen in the appendix. Here, we report a rare case of GCA in the stomach. An 80-year-old man underwent gastroscopy due to epigastric pain and was diagnosed with gastric cancer. He received total gastrectomy and histology showed a mixture of a moderately-differentiated tubular adenocarcinoma, a mucinous adenocarcinoma, and a tumor composed of goblet-like mucinous cells with neuroendocrine differentiation. The tumor volume ratio was about 4:1:5, respectively, and a final diagnosis of GCA was made. The metastasis of the regional lymph node was occupied by only the component of goblet-like cells. GCA should be recognized as a rare histologic subtype of gastric cancer.

A case of hepatocellular carcinoma arising from the intraductal hepatic bile duct without parenchymal lesion.

Hepatocellular carcinoma (HCC) rarely presents as an intraductal tumor with no parenchymal lesions. Here, we present a case of HCC arising from an intrahepatic bile duct. A 74-year-old man who had been treated with direct-acting antiviral therapy for hepatitis C virus infection was referred to our hospital because of elevated serum prothrombin levels induced by vitamin K absence II (PIVKA-II). Initial imaging revealed no findings suspicious of HCC; however, repeat CT six months later revealed dilation of the intrahepatic bile ducts in the lateral segment of the liver. Cholangiography revealed a significant stricture of B3, and biopsy suggested adenocarcinoma. A left hepatectomy was performed with a preoperative diagnosis of intrahepatic cholangiocarcinoma. Although a surface nodule on the lateral segment of the liver, suspicious for intrahepatic metastasis, was found intraoperatively, radical resection was performed. Histopathological examination revealed a tumor filling the intrahepatic bile duct from the stump to the peripheral bile duct, with no infiltration into the liver parenchyma. The surface nodule is a dilated peripheral bile duct filled with a tumor with no extrabiliary invasion. Immunohistochemistry suggested HCC. No tumor lesions were observed in the hepatic parenchyma, and the tumor was finally diagnosed as HCC stemming from the biliary epithelium.

Clinical characteristics of anti-GBM disease with thrombotic microangiopathy: a case report and literature review.

The coexistence of anti-glomerular basement membrane (anti-GBM) disease with thrombotic microangiopathy (TMA) is rarely encountered, and the clinical characteristics of this phenomenon are not well known.A 76-year-old Japanese woman with a history of idiopathic pulmonary disease was diagnosed with anti-GBM disease due to rapidly progressive glomerulonephritis and a positive anti-GBM antibody test result. We treated the patient with hemodialysis, glucocorticoids, and plasmapheresis. During treatment, the patient suddenly became comatose. TMA was then diagnosed because of thrombocytopenia and microangiopathic hemolytic anemia. The activity of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS-13) was retained at 48%. Although we continued the treatment, the patient died of respiratory failure. An autopsy revealed the cause of respiratory failure to be an acute exacerbation of interstitial pneumonia. The clinical findings of the renal specimen indicated anti-GBM disease; however, there were no lesions suggestive of TMA. A genetic test did not reveal an apparent genetic mutation of the atypical hemolytic uremic syndrome.We conducted a literature review of past case reports of anti-GBM disease with TMA. The following clinical characteristics were obtained. First, 75% of the cases were reported in Asia. Second, TMA tended to appear during the treatment course for anti-GBM disease and usually resolved within 12 weeks. Third, ADAMTS-13 activity was retained above 10% in 90% of the cases. Fourth, central nervous system manifestations occurred in more than half of the patients. Fifth, the renal outcome was very poor. Further studies are required to understand the pathophysiology of this phenomenon.

Effects of intrapulmonary viral tropism and cytokine expression on the histological patterns of cytomegalovirus pneumonia.

Pulmonary cytomegalovirus (CMV) infection causes fatal CMV pneumonia (CMVp) in immunocompromised patients; however, the mechanisms underlying CMV-infection-induced pulmonary lesion development remain largely unknown. We examined the relationship between CMVp patterns and intrapulmonary viral tropism, including expression of inflammatory cytokines and related molecules. Double immunohistochemistry of CMV antigen and cellular markers showed that epithelial tropism was associated with a diffuse alveolar damage (DAD) pattern (CMVp-DAD) while stromal tropism was associated with a predominantly interstitial inflammation/fibrosis (IIF) (CMVp-IIF) or a combination of DAD and IIF (CMVp-complex). Transforming growth factor (TGF)-ß1 expression was relevant to CMV-induced tissue injury, and its expression was higher in CMVp-complex and CMVp-IIF than in CMVp-DAD. Expression of integrin ß6 (ITGB6), an adhesion molecule and important activator of TGF-ß1 in interstitial pneumonia, was lost in CMV-infected pneumocytes, especially CMVp-DAD, whereas CMV-negative pneumocytes in CMVp-complex and CMVp-IIF showed overexpression. Diffuse interleukin (IL)-8 up-regulation and strong expression were present in both CMV-infected pneumocytes and stromal cells only in CMVp-IIF cases with marked interstitial neutrophilic infiltration. On the basis of viral tropism and the expression of TGF-ß1, ITGB6, and IL-8, we conclude that CMV-infected pulmonary cells play an important role in the development of diverse CMVp patterns.

Peripherally Inserted Central Catheter-Related Infectious Myositis: A Case Report.

BACKGROUND Peripherally inserted central catheters (PICCs) are commonly used by clinicians in daily practice as a safe and reliable alternative to central venous catheters. While there are advantages to the use of PICCs, such as a low insertion-related complication rate and cost-effectiveness, using PICCs may expose patients to life-threatening severe complications such as a central line-associated bloodstream infection and deep venous thrombosis (DVT). There have been no reports of infectious myositis associated with PICC insertion. CASE REPORT We report a case of infectious myositis related to PICC insertion complicated by brachial DVT in a 43-year-old immunocompromised patient with myelodysplastic syndrome. Despite the administration of broad-spectrum antibiotics, the patient's condition did not improve. He developed septic shock and required emergency excision of the infected and necrotic muscles. Although the pathogen responsible for the infection was unknown, infectious myositis and myonecrosis were observed intraoperatively. Furthermore, histopathological examination revealed evidence of infectious myositis in the biceps brachii and brachial muscles. The septic shock resolved with treatment and the patient survived with residual elbow joint dysfunction. CONCLUSIONS We present a case of infectious myositis related to PICC insertion. We believe that urgent resection of infected and necrotic tissues, rather than broad-spectrum antimicrobial therapy alone, was essential to save the patient's life.

Long-Term Effects of Repeated Social Defeat Stress on Brain Activity during Social Interaction in BALB/c Mice.

Understanding the long-term effects of stress on brain function is crucial for understanding the mechanisms of depression. The BALB/c mouse strain has high susceptibility to stress and is thus an effective model for depression. The long-term effects of repeated social defeat stress (SDS) on BALB/c mice, however, are not clear. Here, we investigated the effects of repeated SDS in male BALB/c mice over the subsequent two weeks. Some defeated mice immediately exhibited social avoidance, whereas anxiety-like behavior was only evident at later periods. Furthermore, defeated mice segregated into two groups based on the level of social avoidance, namely, avoidant and nonavoidant mice. The characteristic of avoidance or nonavoidance in each individual was not fixed over the two weeks. In addition, we developed a semi-automated method for analyzing c-Fos expression in the mouse brain to investigate the effect of repeated SDS on brain activity more than two weeks after the end of the stress exposure. Following social interaction, c-Fos expression was reduced in several brain regions in the defeated mice compared with control mice. The correlation of c-Fos expression among these brain areas, with exception of the medial prefrontal cortex (mPFC) and central amygdala (CeA), was increased in defeated mice, suggesting increased synchrony. Notably, c-Fos expression in the lateral habenula (LHb) was different between mice that exhibited social avoidance from immediately after the repeated SDS and those that exhibited social avoidance only at later periods. These observations provide insight into the long-term effects of social stress on behavior and brain activity.

Epidermal growth factor receptor mutation-positive advanced lung adenocarcinoma presenting with acute respiratory failure diagnosed by thin bronchoscope through transnasal route under high-concentration oxygen mask.

A 59-year-old woman complained of continuous dyspnea. Computed tomography revealed multiple pulmonary nodules, mildly small enlarged mediastinal lymph nodes and a nodule in the liver segment 8. Her dyspnea worsened with respiratory failure 4 days after presentation. Liver biopsy was not possible as she could not hold her breath; thus, we performed bronchoscopy. For biopsy, the pulmonary nodules with a positive bronchus sign were preferred over the mildly small enlarged mediastinal lymph nodes. Bronchoscopy under non-invasive positive pressure ventilation (NPPV) or high-flow nasal cannula (HFNC) was impossible because of the lack of equipment. Therefore, we biopsied via thin bronchoscope through nasal cavity under a high-concentration oxygen mask. Pathological findings revealed epidermal growth factor receptor mutation-positive lung adenocarcinoma. For patients with respiratory failure who cannot undergo bronchoscopy under NPPV or HFNC, thin bronchoscopy through the nasal cavity under a high-concentration oxygen mask may be clinically useful to prevent hypoxaemia during the procedure.

[Primary leptomeningeal gliomatosis treated with temozolomide: a case report].

A 35-year-old man was admitted to our department for loss of consciousness. CT and MRI revealed diffuse enhancement of the subarachnoid space surrounding the brainstem and the cerebellar sulci, without any parenchymal lesions in the brain or the spinal cord. Furthermore, gadolinium-enhanced MRI revealed a nodular lesion with heterogeneous enhancement in the right prepontine cistern, at the site from which a biopsy was obtained via right lateral suboccipital craniotomy on the day following admission. Histopathological examination of the resected specimen revealed glioblastoma multiforme. Based on the radiological and histopathological findings, the patient was diagnosed with primary leptomeningeal gliomatosis (PLG). The patient received temozolomide chemotherapy with concurrent radiotherapy and showed radiological remission, 12 months after diagnosis. However, he developed local recurrence 6 months later and died 23 months after diagnosis. Autopsy findings showed tumor cell infiltration of the leptomeninges, as well as the brain and spinal parenchyma. PLG should be considered in the differential diagnosis in patients with diffuse leptomeningeal enhancement even without parenchymal lesions on radiological imaging. A surgical biopsy is recommended for prompt and accurate diagnosis in such cases.

Preoperative marking of a submillimeter metastatic pulmonary tumor using a mobile computed tomography scan with a navigation system: A case report.

INTRODUCTION AND IMPORTANCE: Preoperative localization of non-palpable lung nodules plays an important role in video assisted thoracic surgery (VATS). Although percutaneous computed tomography (CT)-guided hook wire marking has become widely accepted, it is accompanied by rare but fatal complications such as air embolisms. We herein report a case of a submillimeter pulmonary nodule successfully localized by a mobile CT scan with a navigation system. CASE PRESENTATION: A 40-year-old-man presented with the two right pulmonary nodules 4 years after a radical left nephrectomy for a renal clear cell carcinoma. One of the nodules was too small to palpate and preoperative marking was applied using a mobile CT scan with a navigation system. We successfully performed VATS wedge resection for both nodules and confirmed a pathological diagnosis of a metastasis from the renal cell carcinoma. The maximum pathological size of the smaller nodule was 500 µm. CLINICAL DISCUSSION: Preoperative marking of the lower lobe lesion in the present case was essential for VATS. Our novel technique was helpful for the precise marking without any morbidity. CONCLUSION: Preoperative marking using a mobile CT scan with a navigation system is safe and easily applicable. It might be a useful option for VATS of non-palpable lung nodules.

Prolonged activation of cytomegalovirus early gene e1-promoter exclusively in neurons during infection of the developing cerebrum.

The brain is the major target of congenital cytomegalovirus (CMV) infection. It is possible that neuron disorder in the developing brain is a critical factor in the development of neuropsychiatric diseases in later life. Previous studies using mouse model of murine CMV (MCMV) infection demonstrated that the viral early antigen (E1 as a product of e1 gene) persists in the postnatal neurons of the hippocampus (HP) and cerebral cortex (CX) after the disappearance of lytic infection from non-neuronal cells in the periventricular (PV) region. Furthermore, neuron-specific activation of the MCMV-e1-promoter (e1-pro) was found in the cerebrum of transgenic mice carrying the e1-pro-lacZ reporter construct. In this study, in order to elucidate the mechanisms of e1-pro activation in cerebral neurons during actual MCMV infection, we have generated the recombinant MCMV (rMCMV) carrying long e1-pro1373- or short e1-pro448-EGFP reporter constructs. The length of the former, 1373 nucleotides (nt), is similar to that of transgenic mice. rMCMVs and wild type MCMV did not significantly differed in terms of viral replication or E1 expression. rMCMV-infected mouse embryonic fibroblasts showed lytic infection and activation of both promoters, while virus-infected cerebral neurons in primary neuronal cultures demonstrated the non-lytic and persistent infection as well as the activation of e1-pro-1373, but not -448. In the rMCMV-infected postnatal cerebrum, lytic infection and the activation of both promoters were found in non-neuronal cells of the PV region until postnatal 8 days (P8), but these disappeared at P12, while the activation of e1-pro-1373, but not -448 appeared in HP and CX neurons at P8 and were prolonged exclusively in these neurons at P12, with preservation of the neuronal morphology. Therefore, e1-pro-448 is sufficient to activate E1 expression in non-neuronal cells, however, the upstream sequence from nt -449 to -1373 in e1-pro-1373 is supposed to work as an enhancer necessary for the neuron-specific activation of e1-pro, particularly around the second postnatal week. This unique activation of e1-pro in developing cerebral neurons may be an important factor in the neurodevelopmental disorders induced by congenital CMV infection.