PGC-1α or FNDC5 Is Involved in Modulating the Effects of Aß1-42 Oligomers on Suppressing the Expression of BDNF, a Beneficial Factor for Inhibiting Neuronal Apoptosis, Aß Deposition and Cognitive Decline of APP/PS1 Tg Mice.

Alzheimer's disease (AD) is generally defined as the aberrant production of ß-amyloid protein (Aß) and hyperphosphorylated tau protein, which are deposited in ß-amyloid plaques (APs) and neurofibrillary tangles (NFTs), respectively. Decreased levels of brain-derived neurotrophic factor (BDNF) have been detected in patients with AD compared to control subjects. However, the underlying molecular mechanisms driving the downregulation of the BDNF remain unknown. Therefore, we explored the mechanisms underlying the regulation of BDNF in the neurons of APP/PS1 transgenic (Tg) mice, an AD experimental model. Using the APP/PS1 Tg mice, we found that BDNF expression was markedly downregualted at the age of 3- and 9-month-old. After cerebroventricular injection (i.c.v) of Aß1-42 oligomers into the mice, BDNF was also found to be decreased, which demonstrated the critical roles of the Aß1-42 oligomers in regulating the expression of BDNF. In neuronal culture, peroxisome proliferators-activated receptor γ coactivator 1α (PGC-1α) and fibronectin type III domain-containing 5 (FNDC5) were found to be downregulated by treatment with the Aß1-42 oligomers. In addition, overexpression of either PGC-1α or FNDC5 reversed the suppressive effects of the Aß1-42 oligomers on the expression of BDNF in neuroblastoma 2a (n2a) cells. More importantly, elevating the levels of PGC-1α, FNDC5 or BDNF in the n2a cells counteracted the effects of the Aß1-42 oligomers on neuronal apoptosis. Additionally, intranasal administration BDNF in the APP/PS1 Tg mice decreased the Aß deposition and reduced the cognitive decline of the mice.

[Leukoencephalopathy with cerebral calcification and cysts: a case report and review of literature].

OBJECTIVE: To improve the diagnostic ability of leukoencephalopathy with cerebral calcifications and cysts (LCC), a rare central nervous system disease. METHODS: The clinical manifestations, neuroimages and neuropathological features of a 19-year-old male patient were analyzed. A total of 20 cases from 14 literatures were reviewed. RESULT: The patient was admitted with right limb weakness, cognitive decline, headache and blurred eyesight. Head CT scan showed multiple calcifications, cysts formation and leukoencephalopathy. Brain MRI showed several cysts in bilateral hemisphere, basal ganglia, thalamus and paraventricular areas. A mural nodule was noted inside one of the cyst, which was enhanced on the contrasted MRI. The wall of the cysts was partially enhanced, but not with the fluid inside the cysts. The corresponding CT calcifications foci showed on T1 and T2 with either both hyperintensity or both hypointensity, which was also partial enhanced. Extensive leukoencephalopathy was formed around the cysts and the ventricles. But neither Cho nor NAA changed a lot on MRS. Amplitude diagram of SWI series exhibited multiple round small dark signals all over the affected areas with mixed signals showed in the phase diagram, which indicated both calcifications and microbleeding at the lesions. Neuropathological examinations found no tumor cells in the operated cyst, and showed angiomatous small blood cells were dominant in the cyst wall. Hyaline degenerations, microcalcifications and hemosiderin deposition were observed. No obvious demyelination was discovered, while gliosis, numerous Rosenthal fibers and fibrinoid vascular necrosis were found around the lesions. The clinical, neuroimaging and pathological features of this patient were in accordance with the cases reported in the literatures. CONCLUSIONS: Neuroimaging is the most important method for the diagnosis of LCC. As small vessel lesions are probably closely related to the pathophysiology of LCC, SWI could be recommended to further reveal the etiology of LCC.

[Clinical features and neuroimaging findings of 12 patients with acute disseminated encephalomyelitis involved in corpus callosum].

OBJECTIVE: To summarize the clinical features and neuroimaging findings of the patients with acute disseminated encephalomyelitis (ADEM) involved in corpus callosum (CC) so as to distinguish it from other diseases. METHODS: A total of 12 ADEM patients with the involvement of CC during the period of 2010-2012 were recruited. There were 9 males and 3 females with a mean age of 31±14 years (range: 10-54). Their clinical and neuroimaging features were retrospectively reviewed and all data analyzed by SPSS 18.0. RESULTS: (1) All of them had an acute or subacute onset. Two patients had a history of vaccination and 5 suffered upper respiratory tract infection or diarrhea. (2) The presenting symptoms included fever (n=5), headache (n=4), unsteady gait (n=2), urinary retention (n=1), indifference (n=1) and delirium (n=1). (3) The main clinical symptoms included memory loss (n=9), delirium (n=5), somnolence (n=4), urinary retention (n=9), paraplegia (n=4) and unsteady gait (n=5). (4) The examinations of cerebrospinal fluid (CSF) revealed increased intracranial pressure (n=4), leucocytosis (n=3) and increased protein (n=7) of 7 cases. All oligoclonal bands were negative. (5) The lesions were involved in bilateral CCs in 12 patients. Among them, splenium was the most commonly affected (n=9), secondly stem (n=5) and lastly genu (n=4). For 6 patients, the intracranial lesions were all in their CCs. And among them, 2 cases were involved in spinal cord. Except for CC, there were other focal lesions in brain stem and cerebellum (n=4) and spinal cord (n=6). (6) On magnetic resonance imaging (MRI), all cases showed long T2 signal intensity with blurred images. And among them, 2 cases' lesions in brain were discerned only by diffuse weighing imaging (DWI) or T2 fast fluid-attenuated inversion recovery (T2FLAIR) instead of T2-weighted. The lesions of CCs showed on gadolinium-enhanced MRI were significantly enhanced and the shapes were sheet-like (4/6). Spinal cord lesions was found in 6 cases and most spinal cord lesions were discontinuous. And the number of spinal cord segments with lesions was from 4 to 8. The shapes of lesions of spinal cord showed on enhanced MRI were like thin line. (7) Most of them were misdiagnosed as viral encephalitis (n=5), tuberculous meningoencephalitis (n=1) and brain neoplasms (n=2). And another case was admitted into urology surgery ward due to urinary retention. CONCLUSION: There are three key points about the characteristics of the ADEM patients with CC lesions: (1) They may have an adult male preponderance. The distinctive symptoms include fever, headache, delirium, somnolence, memory loss, unsteady gait and urination disorders, etc.. (2) The number of lesions on brain MRI can be multiple or single, especially the lesions of CC (mostly in splenium). On MRI, all cases showed long T2 signal intensity with blurred images so that DWI and T2 FLAIR may have a higher efficiency of detecting the lesions. In particular, multiple lesions may be all enhanced or not enhanced at equal pace on enhanced MRI. (3) In ADEM patients with CC lesions, many indices of CSF chemical examination, such as increased intracranial pressure, leucocytosis, increased protein, low sugar and low chloride, indicate the presence of intracranial infective diseases. Therefore they are most likely to be misdiagnosed as viral encephalitis or tuberculous meningoencephalitis. However, CC is not the predilection site for viral encephalitis since CC belongs to white matter but not gray matter. So ADEM should be a more appropriate diagnosis for these cases.

[The clinical features, neuroimaging findings and pathological characteristics of 26 patients with pathologically proven tumor-like inflammatory demyelinating diseases].

OBJECTIVE: To summarize the clinical features, neuroimaging findings and pathological characteristics of 26 patients with tumor-like inflammatory demyelinating diseases (TIDD) confirmed by histopathology for better diagnosis and differential diagnosis. METHODS: The clinical features, neuroimaging findings and pathological characteristics of 26 patients (14 male, 12 female) with pathologically proven TIDD (24 brain-type and 2 spinal cord-type) were retrospectively analysed. RESULTS: The mean onset age was 6 - 69 (36.7 ± 13.8) years. Twenty-one patients had good prognosis with a median followed-up duration of 51.0 months. Two patients were died of post-operative complication and pulmonary infection respectively and the remaining 3 patients were lost to followed up. The TIDD patients almost showed monophasic clinical setting. Headache, indifference accompanied with hypothesis were the commonest initial symptoms. The positive or abnormal rates of cerebrospinal fluid oligoclonal bands (OCB) and myelin basic protein (MBP) in TIDD patients were high. The involvements of bilateral and multi-lesions were commonest in TIDD (61.5%, 65.4% respectively). Twenty-two patients with CT unenhanced scanning showed hypodense lesions. Long T(1) and long T(2) signal intensity was showed on MRI and most cases appeared round-like lesion in shape. According to the shape of enhancement of the 23 patients performed with contrast agents, 11 were shown with open-ring enhancement, 4 cases (including 2 accompanied with open-ring enhancement) with complete ring enhancement, 3 with asymmetrical dotted enhancement, 2 with diffused even enhancement, and no enhancement was seen in the other 6. Furthermore, 14 cases with DWI and 12 with FLAIR all appeared hyperdensity. The typical pathological changes were demyelinating, perivascular inflammatory cells infiltration and reactive gliosis. Occasionally, the Creutzfeldt cells were also found in brain tissue of some patients. CONCLUSIONS: TIDD is a distinct demyelinating disease entity. In spite of being apt to be confused with the neoplasm in brain and spinal cord. TIDD has its own-features, for example, OCB is frequently positive in patients with TIDD and the level of MBP may be significantly increased. Furthermore, the involvements of bilateral and multi-lesions are the common in TIDD, and most cases showed open-ring enhancement or complete rim enhancement on MRI. In addition, all cases present hypodense lesions on unenhanced CT and patients with hyperdense seemed not to be considered as TIDD.

[The relationship between prion protein gene codon 129 polymorphism and Alzheimer's disease].

OBJECTIVE: To examine the relationship between prion protein gene (PRNP) codon 129 polymorphism and Alzheimer's disease (AD) by means of meta-analysis. METHODS: Odds ratios (OR) of prion protein gene codon 129 genotype distribution in AD patients against healthy control was analysed. All the relevant studies were identified and poor-qualified studies were eliminated. A meta-analysis software, Review Manager 4.2 was applied for investigating heterogeneity among individual studies and summarizing effects across studies. RESULTS: A total of 4 studies including 1095 patients and 940 controls were included but with rectification 972 cases and 658 controls of 3 studies were included. No heterogeneity among the studies was found. The pooled Peto OR (with 95% CI) of (MM + VV) vs MV is 1.10 (95% CI 0.89-1.35, P = 0.38), while the pooled Peto OR of V* vs MM is 0.80 (95% CI 0.65-0.98, P = 0.03) and the pooled Peto OR of M* vs VV is 1.38 (95% CI 1.01-1.89, P = 0.04). CONCLUSION: In European population, PRNP M and V homozygosity is not statistically significantly associated with the onset of AD. M/* genotype is associated with increased risk of AD while V/* genotype is associated with a decreased risk of AD.