Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor regulate the interaction between astrocytes and Schwann cells at the trigeminal root entry zone

The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes.Its special anatomical and physiological structure renders it susceptible to nerve injury.The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone.This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions.Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor.In monoculture,glial cell line-derived neurotrophic factor promoted the migration of Schwann cells,but it did not have effects on the migration of astrocytes.In the co-culture system,glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells.Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes.However,in the co-culture system,brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree.These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone.This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions.

Novel mutations in LRRC23 cause asthenozoospermia in a nonconsanguineous family

The cause of asthenozoospermia(AZS)is not well understood because of its complexity and heterogeneity.Although some gene mutations have been identified as contributing factors,they are only responsible for a small number of cases.Radial spokes(RSs)are critical for adenosine triphosphate-driven flagellar beating and axoneme stability,which is essential for flagellum motility.In this study,we found novel compound heterozygous mutations in leucine-rich repeat-containing protein 23(LRRC23;c.1018C>T:p.Q340X and c.881_897 Del:p.R295Gfs*32)in a proband from a nonconsanguineous family with AZS and male infertility.Diff-Quik staining and scanning electron microscopy revealed no abnormal sperm morphology.Western blotting and immunofluorescence staining showed that these mutations suppressed LRRC23 expression in sperm flagella.Additionally,transmission electron microscopy showed the absence of RS3 in sperm flagella,which disrupts stability of the radial spoke complex and impairs motility.Following in vitro fertilization and embryo transfer,the proband’s spouse achieved successful pregnancy and delivered a healthy baby.In conclusion,our study indicates that two novel mutations in LRRC23 are associated with AZS,but successful fertility outcomes can be achieved by in vitro fertilization-embryo transfer techniques.

Clinical and genetic heterogeneity of adult polyglucosan body disease caused by GBE1 biallelic mutations in China

Adult polyglucosan body disease(APBD)is a rare and highly heterogeneous glycogen storage disorder due to biallelic variants in GBE1.1 Typical APBD presentations include gait abnormalities with polyneuropathy,leukodystrophy,neurogenic bladder,and mild cognitive impairment.Differential diagnosis of APBD encompasses a large spectrum of conditions including axonal and demyelinating sensorimotor polyneuropathy,progressive spastic paraparesis,and leukodystrophies.