Recessive mutations in SPTBN2 implicate β-III spectrin in both cognitive and motor development.

β-III spectrin is present in the brain and is known to be important in the function of the cerebellum. Heterozygous mutations in SPTBN2, the gene encoding β-III spectrin, cause Spinocerebellar Ataxia Type 5 (SCA5), an adult-onset, slowly progressive, autosomal-dominant pure cerebellar ataxia. SCA5 is sometimes known as "Lincoln ataxia," because the largest known family is descended from relatives of the United States President Abraham Lincoln.

Faciobrachial dystonic seizures precede Lgi1 antibody limbic encephalitis.

Objective: To describe a distinctive seizure semiology that closely associates with voltage-gated potassium channel (VGKC)-complex/Lgi1 antibodies and commonly precedes the onset of limbic encephalitis (LE).

Methods: Twenty-nine patients were identified by the authors (n = 15) or referring clinicians (n = 14). The temporal progression of clinical features and serum sodium, brain magnetic resonance imaging (MRI), positron emission tomography/single photon emission computed tomography, and VGKC-complex antibodies was studied.

The survival of neural precursor cell grafts is influenced by in vitro expansion.

Embryonic neural precursor cells (ENPs) provide a potential alternative for transplantation in neurodegenerative diseases, as they can be expanded in culture, avoiding many of the practical obstacles that limit the application of transplanting primary neurones. However, grafts of ENPs into animal models show variable survival and limited differentiation into neurones. The effect of expansion time on their ability to survive and differentiate may be an important factor in this and has not been examined directly.

Decreased hippocampal cell proliferation in R6/1 Huntington's mice.

In order to ascertain whether disturbances of neurogenesis occur in chronic neurodegenerative disorders, we assessed hippocampal cell proliferation in the R6/1 transgenic mouse model of Huntington's disease (HD). Using BrdU labelling for dividing cells at two different time points (5 and 20 weeks) in transgenic and wild type control mice, we have shown that cell proliferation in the hippocampus was similar in younger asymptomatic R6/1 mice and wild type controls, but that older R6/1 mice had significantly fewer BrdU cells than controls. Such a decrease in cell proliferation may be relevant to some of the deficits seen in these mice, although further work is needed to prove this.

Long-term hibernation of human fetal striatal tissue does not adversely affect its differentiation in vitro or graft survival: implications for clinical trials in Huntington's disease.

Transplantation of human fetal CNS tissue is a promising therapy for neurodegenerative conditions such as Huntington's disease (HD), but its widespread adoption is limited by restricted tissue availability. One method of overcoming this problem would be to store the tissue in hibernation medium, an approach that we reported previously for human fetal striatal tissue stored for up to 24 h. We now demonstrate the feasibility of storing such tissue for up to 8 days in hibernation medium.

Migration and differentiation of transplanted human neural precursor cells.

In this study we have examined the migration and phenotypic differentiation of human expanded neural precursors (hENPs) when transplanted into the intact adult rat brain. Primary human embryonic cortical cells and hENPs derived from the same source but expanded epigenetically in culture for two different time periods were transplanted into the rodent striatum and hippocampus. Histological analysis showed that overall the number of neurons decreased with time spent in culture prior to transplantation within the core of the graft regardless of site of implantation.

GABAergic immunoreactivity is predominant in neurons derived from expanded human neural precursor cells in vitro.

Neural precursor cells have been previously isolated from the developing human nervous system and their properties studied both in vitro and in transplantation paradigms in vivo. However, their ability to differentiate into neurons of different neurochemical phenotypes remains poorly defined. In this study, the default in vitro neuronal differentiation of hENPs derived from five different regions of the human embryonic brain (cerebral cortex, striatum, cerebellum, ventral mesencephalon, and spinal cord) was studied after varying periods of time in culture.

Transplantation of expanded neural precursor cells from the developing pig ventral mesencephalon in a rat model of Parkinson's disease.

Neural precursor cell populations can be expanded in vitro under the influence of growth factors, and may be of use to replace cells lost to neurodegenerative conditions such as the dopaminergic neurons in Parkinson's disease (PD). We explore here whether expanding neural precursor cells from the region in which nigral dopaminergic neurones emerge in normal development renders them more likely to differentiate into TH-positive neurones when transplanted in a rat model of PD. Embryonic neural precursor cells (ENPs) were isolated from the developing pig ventral mesencephalon (VM) at two different gestational ages and were implanted into the striatum or the substantia nigra of cyclosporin A-immunosuppressed, 6-hydroxydopamine-lesioned rats, which were sacrificed 9 or 18 weeks later.

The potential for circuit reconstruction by expanded neural precursor cells explored through porcine xenografts in a rat model of Parkinson's disease.

Neural precursors with the properties of neural stem cells can be isolated from the developing brain, can be expanded in culture, and have been suggested as a potential source of cells for neuronal replacement therapies in degenerative disorders such as Parkinson's disease (PD). Under such conditions an improved spectrum of functional benefit may be obtained through homotypic reconstruction of degenerated neural circuitry, and to this end we have investigated the potential of expanded neural precursor cells (ENPs) to form long axonal projections following transplantation in the 6-hydroxydopamine-lesioned rat model of PD. ENPs have been isolated from the embryonic pig, since implantation in a xenograft environment is thought to favor axonal growth.

Neural cells from primary human striatal xenografts migrate extensively in the adult rat CNS.

Primary neural cells do not appear to migrate significantly following transplantation into the adult rodent CNS, which is in contrast to expanded neural precursor cells where migration is well-documented. However, most transplant studies of primary neural tissue have been performed in an allograft situation in which it is difficult to identify graft-derived cells. We have, therefore, used a xenograft paradigm to investigate the potential for cells derived from grafts of primary human fetal striatal tissue (gestational age of 66-72 days) to migrate following intrastriatal transplantation in an athymic adult rat model of Huntington's disease.