Glial-derived neurotrophic factor rescues calbindin-D28k-immunoreactive neurons in alcohol-treated cerebellar explant cultures

Abstract

Ethanol exposure during development leads to alterations in neuronal differentiation and profound neuronal loss in multiple regions of the developing brain. Although differentiating Purkinje cells of the cerebellum are particularly vulnerable to ethanol exposure, the mechanisms that ameliorate ethanol‐induced Purkinje cell loss have not been well defined. Previous research indicates that glial‐derived neurotrophic factor (GDNF), a member of the transforming growth factor‐β family, promotes the survival of several neuronal populations, including cerebellar Purkinje cells. Therefore, we examined whether GDNF could attenuate ethanol‐induced Purkinje cell loss in an in vitro model system using calbindin‐D28k‐immunoreactivity as a specific marker for Purkinje cells. We found that ethanol led to a significant dose‐related decline in calbindin‐D28k‐immunoreactive cells in explant cultures of the developing cerebellum. However, concurrent administration of GDNF led to a significant rescue of calbindin‐D28k‐immunoreactive cells. Therefore, our results suggest that GDNF prevents ethanol‐associated Purkinje cell loss. © 1997 John Wiley & Sons, Inc. J Neurobiol 33: 835–847, 1997

Neurogenic potential of human mesenchymal stem cells revisited: analysis by immunostaining, time-lapse video and microarray

“…In most cases, cell type-specific markers have been deemed to be reliable in the identification of particular cell types in a given context, but they can be misleading in other contexts. For instance, in the CNS, the calcium binding protein calbindin is used as marker for the horizontal cells, a population of interneurons in the retina (Matsuda and Cepko, 2004), but it is also the standard marker for Purkinje projection neurons in the cerebellum (McAlhany et al, 1997). A cell expressing calbindin cannot be classified as a Purkinje cell (or horizontal cell) if its origin is not known or, worse, if it is different from both retina and cerebellum.…”

Selective Glial Cell Line-Derived Neurotrophic Factor Production in Adult Dopaminergic Carotid Body CellsIn Situand after Intrastriatal Transplantation

“…Among these factors, GDNF has received special attention because of its potent effects on dopaminergic neurons (Lin et al, 1993). Exogenous GDNF also protects neurons from death after transient brain ischemia or in Huntington models (Araujo and Hilt, 1997;Miyazaki et al, 1999;Alberch et al, 2002), supports the survival of axotomized spinal and corticospinal motoneurons (Henderson et al, 1994;Giehl et al, 1998;Yuan et al, 2000), and retards toxic and hereditary Purkinje cell degeneration (McAlhany et al, 1997;Tolbert and Clark, 2003). In this article, we show that, besides being highly dopaminergic, CB glomus cells contain more GDNF than any other structure studied in the adult rodent and that the ability to synthesize GDNF is maintained in the CB of aged animals or after chronic MPTP treatment.…”

Mechanisms of ethanol-induced degeneration in the developing, mature, and aging cerebellum

“…The relevance of the neurotrophic support to the developing cerebellum has also been pointed out by studies showing neuroprotection against ethanolinduced toxicity in cultured neonatal Purkinje and granule cells by several neurotrophic factors (154)(155)(156). Furthermore, transgenic mice overexpressing NGF showed less ethanol-mediated loss of Purkinje neurons in the anterior superior vermis than the wild-type animals after similar ethanol exposure on PD4-5 (157).…”