Spontaneous mutation in the lysosomal acid phosphatase 2 (Acp2) mouse (nax--naked-ataxia mutant mouse) correlates with severe cerebellar defects including ataxia, reduced size and abnormal lobulation as well as Purkinje cell (Pc) degeneration. Loss of Pcs in the nax cerebellum is compartmentalized and harmonized to the classic pattern of gene expression of the cerebellum in the wild type mouse....

Toluene is a neurotoxic organic solvent widely used in industry. Acute toluene administration in rats induced a significant increase in the numbers of neural cells immunostained for p75NTR in several brainstem regions, such as the raphe magnus and the nucleus of the solitary tract, as well as in the lateral reticular, gigantocellular, vestibular and ventral cochlear nuclei, without any in the f...

The generation of biologically active proteins by regulated intramembrane proteolysis is a highly conserved mechanism in cell signaling. Presenilin-dependent gamma-secretase activity is responsible for the intramembrane proteolysis of selected type I membrane proteins, including beta-amyloid precursor protein (APP) and Notch. A small fraction of intracellular domains derived from both APP and N...

Altered neurotrophism in diabetic peripheral neuropathy (DPN) is associated in part with substantial degenerative changes in Schwann cells (SCs) and an increased expression of the p75 neurotrophin receptor (p75NTR). Caveolin-1 (Cav-1) is highly expressed in adult SCs, and changes in its expression can regulate signaling through Erb B2, a co-receptor that mediates the effects of neuregulins in p...

The p75 neurotrophin receptor (p75NTR) is an alpha- and gamma-secretase substrate expressed preferentially in the cholinergic neurons of the nucleus basalis of Meynert, the hippocampus, and the cerebellum of the adult brain. Mutations of the gamma-secretase, presenilin, have been implicated in familial Alzheimer's disease. Furthermore, oxidative and inflammatory injury to the cholinergic neuron...

The trophic effect of continuous intraventricular infusion of nerve growth factor (NGF) on morphology of the basal forebrain (BF) cholinergic neurons was tested in 4- and 28-month-old male Wistar rats. All studies were conducted using behaviorally uncharacterized animals from the same breeding colony. Immunohistochemical procedure for choline acetyltransferase (ChAT) and p75NTR receptor has bee...

The majority of newborn neurons migrate from their birthplace to final destination in the developing brain. Migration of cerebellar granule cells (CGCs) requires multiple factors. Mature brain-derived neurotrophic factor (BDNF) positively regulates the proliferation, migration, survival and differentiation of CGCs in rodents. However, the role of the BDNF precursor, proBDNF, in neuronal develop...

Although traditionally little attention has been paid to the interplay between neurotrophins and the cell cycle, a number of recent findings suggest an important role for these growth factors in the regulation of this aspect of the cellular physiology. In this article, we review the evidence from a number of studies that neurotrophins can influence cell cycle progression or mitotic cycle arrest...

Nerve growth factor (NGF) is suggested to be neuroprotective after nerve injury; however, retinal ganglion cells (RGC) degenerate following optic-nerve crush (ONC), even in the presence of increased levels of endogenous NGF. To further investigate this apparently paradoxical condition, a time-course study was performed to evaluate the effects of unilateral ONC on NGF expression and signaling in...