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Sex-specific pleiotropic changes in emotional behavior and alcohol consumption in human α-synuclein A53T transgenic mice during early adulthood

Kalinichenko LS, Kohl Z, Mühle C, Hassan Z, Hahn A, Schmitt EM, et al.

J Neurochem, 2024 Mar;168(3):269-287.
PMID: 38284431 DOI: 10.1111/jnc.16051

Point mutations in the α-synuclein coding gene may lead to the development of Parkinson's disease (PD). PD is often accompanied by other psychiatric conditions, such as anxiety, depression, and drug use disorders, which typically emerge in adulthood. Some of these point mutations, such as SNCA and A30T, have been linked to behavioral effects that are not commonly associated with PD, especially regarding alcohol consumption patterns. In this study, we investigated whether the familial PD point mutation A53T is associated with changes in alcohol consumption behavior and emotional states at ages not yet characterized by α-synuclein accumulation. The affective and alcohol-drinking phenotypes remained unaltered in female PDGF-hA53T-synuclein-transgenic (A53T) mice during both early and late adulthood. Brain region-specific activation of ceramide-producing enzymes, acid sphingomyelinase (ASM), and neutral sphingomyelinase (NSM), known for their neuroprotective properties, was observed during early adulthood but not in late adulthood. In males, the A53T mutation was linked to a reduction in alcohol consumption in both early and late adulthood. However, male A53T mice displayed increased anxiety- and depression-like behaviors during both early and late adulthood. Enhanced ASM activity in the dorsal mesencephalon and ventral hippocampus may potentially contribute to these adverse behavioral effects of the mutation in males during late adulthood. In summary, the A53T gene mutation was associated with diverse changes in emotional states and alcohol consumption behavior long before the onset of PD, and these effects varied by sex. These alterations in behavior may be linked to changes in brain ceramide metabolism.

Matched MeSH terms: Sphingomyelin Phosphodiesterase
Fulltext Bioactives from probiotics for dermal health: functions and benefits

Lew LC, Liong MT

J Appl Microbiol, 2013 May;114(5):1241-53.
PMID: 23311666 DOI: 10.1111/jam.12137

Probiotics have been extensively reviewed for decades, emphasizing on improving general gut health. Recently, more studies showed that probiotics may exert other health-promoting effects beyond gut well-being, attributed to the rise of the gut-brain axis correlations. Some of these new benefits include skin health such as improving atopic eczema, atopic dermatitis, healing of burn and scars, skin-rejuvenating properties and improving skin innate immunity. Increasing evidence has also showed that bacterial compounds such as cell wall fragments, their metabolites and dead bacteria can elicit certain immune responses on the skin and improve skin barrier functions. This review aimed to underline the mechanisms or the exact compounds underlying the benefits of bacterial extract on the skin based on evidences from in vivo and in vitro studies. This review could be of help in screening of probiotic strains with potential dermal enhancing properties for topical applications.

Matched MeSH terms: Sphingomyelin Phosphodiesterase/pharmacology
Fulltext Four novel p.N385K, p.V36A, c.1033-1034insT and c.1417-1418delCT mutations in the sphingomyelin Phosphodiesterase 1 (SMPD1) gene in patients with types A and B Niemann-Pick disease (NPD)

Manshadi MD, Kamalidehghan B, Keshavarzi F, Aryani O, Dadgar S, Arastehkani A, et al.

Int J Mol Sci, 2015 Mar 24;16(4):6668-76.
PMID: 25811928 DOI: 10.3390/ijms16046668

BACKGROUND: Types A and B Niemann-Pick disease (NPD) are autosomal-recessive lysosomal storage disorders caused by the deficient activity of acid sphingomyelinase due to mutations in the sphingomyelin phosphodiesterase 1 (SMPD1) gene.
METHODS: In order to determine the prevalence and distribution of SMPD1 gene mutations, the genomic DNA of 15 unrelated Iranian patients with types A and B NPD was examined using PCR, DNA sequencing and bioinformatics analysis.
RESULTS: Of 8 patients with the p.G508R mutation, 5 patients were homozygous, while the other 3 were heterozygous. One patient was heterozygous for both the p.N385K and p.G508R mutations. Another patient was heterozygous for both the p.A487V and p.G508R mutations. Two patients (one homozygous and one heterozygous) showed the p.V36A mutation. One patient was homozygous for the c.1033-1034insT mutation. One patient was homozygous for the c.573delT mutation, and 1 patient was homozygous for the c.1417-1418delCT mutation. Additionally, bioinformatics analysis indicated that two new p.V36A and p.N385K mutations decreased the acid sphingomyelinase (ASM) protein stability, which might be evidence to suggest the pathogenicity of these mutations.
CONCLUSION: with detection of these new mutations, the genotypic spectrum of types A and B NPD is extended, facilitating the definition of disease-related mutations. However, more research is essential to confirm the pathogenic effect of these mutations.

Matched MeSH terms: Sphingomyelin Phosphodiesterase/genetics*
Fulltext Ursodeoxycholic acid upregulates ERK and Akt in the protection of cardiomyocytes against CoCl2

Hanafi NI, Mohamed AS, Md Noor J, Abdu N, Hasani H, Siran R, et al.

Genet. Mol. Res., 2016 Jun 17;15(2).
PMID: 27323195 DOI: 10.4238/gmr.15028150

Ursodeoxycholic acid (UDCA) is used to treat liver diseases and demonstrates cardioprotective effects. Accumulation of the plasma membrane sphingolipid sphingomyelin in the heart can lead to atherosclerosis and coronary artery disease. Sphingomyelinases (SMases) break down sphingomyelin, producing ceramide, and inhibition of SMases activity can promote cell survival. We hypothesized that UDCA regulates activation of ERK and Akt survival signaling pathways and SMases in protecting cardiac cells against hypoxia. Neonatal cardiomyocytes were isolated from 0- to 2-day-old Sprague Dawley rats, and given 100 μM CoCl2, 150 μM H2O2, or placed in a hypoxia chamber for 24 h. The ameliorative effects of 100-μM UDCA treatment for 12 h were then assessed using MTS, QuantiGene Plex (for Smpd1 and Smpd2), and SMase assays, beating rate assessment, and western blotting (for ERK and Akt). Data were analyzed by the paired Student t-tests and one-way analyses of variance. Cell viability decreased significantly after H2O2 (85%), CoCl2 (50%), and hypoxia chamber (52%) treatments compared to the untreated control (100%). UDCA significantly counteracted the effects of chamber- and CoCl2- induced hypoxia on viability and beating rate. However, no significant differences were observed in acid SMase gene and protein expression between the untreated, CoCl2, and UDCA-CoCl2 groups. In contrast, neutral SMase gene and protein expression did significantly differ between the latter two groups. ERK and Akt phosphorylation was higher in hypoxic cardiomyocytes treated with UDCA than those given CoCl2 alone. In conclusion, UDCA regulates the activation of survival signaling proteins and SMases in neonatal rat cardiomyocytes during hypoxia.

Matched MeSH terms: Sphingomyelin Phosphodiesterase/metabolism
Fulltext Proteinases in Naegleria Fowleri (strain NF3), a pathogenic amoeba: a preliminary study

Mat Amin N

Trop Biomed, 2004 Dec;21(2):57-60.
PMID: 16493399

Naegleria fowleri is a free-living amoeba, known as a causative agent for a fatal disease of the central nervous system (CNS) in man such as Primary amoebic meningoencephalitis (PAM). Factors contributing to its pathogenicity and its distribution in the environment have been investigated by previous researchers. In case of its pathogenicity, several enzymes such as phospolipase A and sphingomyelinase, have been proposed to probably act as aggressors in promoting PAM but no study so far have been conducted to investigate the presence of proteinase enzyme in this amoeba although a 56kDa cystein proteinase enzyme has been identified in Entamoeba histolytica as an important contributing factor in the amoeba's virulence. In this preliminary study, a pathogenic amoeba, Naegleria fowleri (strain NF3) was examined for the presence of proteinases. Samples of enzymes in this amoeba were analysed by electrophoresis using SDS-PAGE-gelatin gels. The results showed that this amoeba possesses at least two high molecular weight proteinases on gelatin gels; their apparent molecular weights are approximately 128 kDa and approximately 170 kDa. Band of approximately 128 kDa enzyme is membrane-associated and its activity is higher at alkaline pH compared with lower pH; at lower pH, its activity is greatly stimulated by DTT. The approximately 170 kDa band enzyme appears to be inactivated at pH 8.0, at lower ph its activity is higher and DTT-dependance. The activity of this enzyme is partially inhibited by inhibitor E-64 but markedly inhibited to antipain suggesting it belongs to the cysteine proteinase group.

Matched MeSH terms: Sphingomyelin Phosphodiesterase