Overexpression of SMN2 Gene in Motoneuron-Like Cells Differentiated from Adipose-Derived Mesenchymal Stem Cells by Ponasterone A.

Cell therapy and stem cell transplantation strategies have provided potential therapeutic approaches for the treatment of neurological disorders. Adipose-derived mesenchymal stem cells (ADMSCs) are abundant adult stem cells with low immunogenicity, which can be used for allogeneic cell replacement therapies. Differentiation of ADMSCs into acetylcholine-secreting motoneurons (MNs) is a promising treatment for MN diseases, such as spinal muscular atrophy (SMA), which is associated with the level of SMN1 gene expression. The SMN2 gene plays an important role in MN disorders, as it can somewhat compensate for the lack of SMN1 expression in SMA patients. Although the differentiation potential of ADMSCs into MNs has been previously established, overexpression of SMN2 gene in a shorter period with a longer survival has yet to be elucidated. Ponasterone A (PNA), an ecdysteroid hormone activating the PI3K/Akt pathway, was studied as a new steroid to promote SMN2 overexpression in MNs differentiated from ADMSCs. After induction with retinoic acid, sonic hedgehog, forskolin, and PNA, MN phenotypes were differentiated from ADMSCs, and immunochemical staining, specific for ß-tubulin, neuron-specific enolase, and choline acetyltransferase, was performed. Also, the results of real-time PCR assay indicated nestin, Pax6, Nkx2.2, Hb9, Olig2, and SMN2 expression in the differentiated cells. After 2 weeks of treatment, cultures supplemented with PNA showed a longer survival and a 1.2-fold increase in the expression of SMN2 (an overall 5.6-fold increase; *P ≤ 0.05), as confirmed by the Western blot analysis. The PNA treatment increased the levels of ChAT, Isl1, Hb9, and Nkx2 expression in MN-like cells. Our findings highlight the role of PNA in the upregulation of SMN2 genes from MSC-derived MN-like cells, which may serve as a potential candidate in cellular therapy for SMA patients.

Early infantile presentation of 3-methylglutaconic aciduria type 1 with a novel mutation in AUH gene: A case report and literature review.

3-Methylglutaconic aciduria is a member of inborn errors of leucine metabolism pathway. 3-Methylglutaconic aciduria type I (MGA1) causes neurological problems which are present during infancy or childhood but the diagnosis may be delayed until adulthood. Here we report a 3years old patient with developmental delay from a relative parent's that his medical evaluations include analyses of urinary organic acid and blood acylcarnitine showed high level of 3-methylglutacoic acid, 3-hydroxyisovaleric acid and increased level of 3-hydroxyisovalerylcarnitine respectively. Further evaluation and genetic tests revealed a novel homozygous mutation of variant c.179del G (p.Gly60Valfs*12) in exon 1 of the AUH gene that was compatible with the diagnosis of MGA1. In segregation analysis of his family, both parents were heterozygous for the respective mutation, confirming obligate parental carrier status and segregation of the mutation.

Sudden impolite behavior in a polite girl: a case report.

In this case we present a previously healthy child with sudden behavioral change and acute confusional state (ACS). ACS is a neurologic emergency. The clinical manifestations of ACS are; confused affect, limited verbal response, disturbance in performing orders, some automatism, stable vital signs and absence of tonic-clonic movements and it has a wide range of differential diagnosis which should be assessed by detailed medical history, medical examination and laboratory tests. The only abnormal test found in this patient, was cerebrospinal fluid abnormality, consistent with viral encephalitis.

Selenium and intractable epilepsy: is there any correlation?

Oxidative stress and generation of reactive oxygen species are strongly implicated in a number of neuronal and neuromuscular disorders, including epilepsy. The functions of selenium as an antioxidant trace element are believed to be carried out by selenoproteins that possess antioxidant activities and the ability to promote neuronal cell survival. Because of this protective role of selenium against oxidative damage, a case-control study was designed to compare its serum level between intractable epileptic patients and normal subjects. Eighty patients who met the criteria of intractable epilepsy were compared with a normal control group of the same age, socioeconomic level, and place of living. Serum selenium level was measured with an atomic absorption spectrophotometer. The mean (+/- S.D.) of serum selenium were 68.88 (+/-17.58) ng/mL and 85.93 (+/-13.93) ng/mL in the patient and control groups respectively. Independent sample t test with P < 0.05 indicated a significant lower mean of serum selenium in the patient group compared with that of the normal control group. However, there was no association between serum selenium and some suggested predictive factors of intractable seizures, including age at the onset of seizures, neonatal seizure, neurologic impairment, and etiology of epilepsy. Measurement of serum selenium in patients with intractable epilepsy should be considered.

Extensive Mongolian spots: a clinical sign merits special attention.

Although typical and limited Mongolian spots are benign skin markings at birth which fade and disappear as the child grows, extensive Mongolian spots deserve special attention as possible indications of associated inborn error of metabolism. A few cases of extensive Mongolian spots in association with inheritable storage diseases have been reported. Some hypotheses have been put forward, but further investigation is necessary to elucidate the causative factors. This report describes three infants with generalized Mongolian spots, two infants with GM1 gangliosidosis type 1, and one in association with Hurler syndrome. Findings of generalized Mongolian spots in newborns may lead to an early detection and early treatment before irreversible organ damage occurs.