Nerve growth factor and brain-derived neurotrophic factor in human paediatric hemimegalencephaly.

Paediatric hemimegalencephaly (HME) is a congenital central nervous system (CNS) disorder, characterized by monolateral cerebral hemisphere enlargement, intractable seizures starting in the post-neonatal period, and mental retardation associated with neuropathological anomalies (mainly cortical thickness and lack of lamination). Nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) are two neurotrophic factors produced in the mammalian CNS that are involved in the survival, development, and function of a variety of brain cells. In the present study, we found increased cerebral tissue levels of NGF and BDNF in 4 infants with HME; these changes appear to be also associated with abnormal NGF-receptor expression in subcortical blood vessels. Moreover, the marked reduction of cortical choline acetyltransferase immunoreactivity is strongly suggestive of a dysregulation in the NGF differentiative activity in this site that could lead to the pathogenesis of HME.

Nerve growth factor serum level is reduced in patients with sensorineural hearing impairment: possible clinical implications.

Nerve growth factor (NGF) is the first and best characterised member of a family of neurotrophic factor. NGF is produced by numerous cells and it is present in physiologically relevant amounts in the bloodstream. It is known to promote the survival of peripheral sensory neurons and can be potentially useful as a therapeutic agent in neuronal system. On the both these observations we based our hypothesis that low circulating NGF might lead to sensorineural hearing loss (SNHL). To address this question we measured the levels of NGF in the bloodstream of patients affected by SNHL. The results showed that the amount of circulating NGF in these patients is significantly lower compared to levels found in patients not affected by this deficit. The results of the present study demonstrated that NGF might be a useful candidate for preventing the damage and promoting recovery or degeneration of the auditory pathways in humans.

Developmental expression of nerve growth factor in the eye of rats affected by inherited retinopathy: correlative aspects with retinal structural degeneration.

We have previously reported that exogenous administration of nerve growth factor (NGF) in C3H/HeJ mouse strain affected by retinitis pigmentosa (RP) delayed retinal degeneration, suggesting that NGF may be implicated in retinal development. Whether NGF is present in the developing eye was not investigated. To address this question we have used Royal College of Surgeons (RCS) rats, characterised by photoreceptor loss during postnatal life. The results of these studies showed that while the thickness of the outer nuclear layer (ONL) of RCS is comparable to controls, while the amount of NGF expressed in the eye of this mutant rat is significant lower, as compared to control eye. This observation suggests that the lower presence of NGF in the eye of RCS rats during early postnatal life might be one critical key factor implicated in RP. The results of these studies will be presented and discussed.

Bromodeoxyuridine and methylazoxymethanol exposure during brain development affects behavior in rats: consideration for a role of nerve growth factor and brain derived neurotrophic factor.

Rats prenatally exposed to the neurotoxins methylazoxymethanol (MAM) or 5-Bromo-2'-deoxyuridine (BrdU) are used as animal models of brain maldevelopment. We administered in rats MAM (20 mg/kg), or BrdU (100 mg/kg) or both at gestational day 11. Locomotion was not affected by any prenatal treatment whereas learning was delayed in the Morris maze in MAM animals. BrdU induced decreased NGF and BDNF levels in the hippocampus. In the parietal cortex prenatal BrdU administration induced NGF potentation associated with decreased BDNF. Animals treated with both MAM and BrdU showed also an increased immunopositivity for choline acetyltransferase (ChAT) and low affinity neurotrophins' receptor (p75) in the septum and Meynert's nuclei. These findings suggest that embryonic exposure to MAM and/or BrdU may be useful for studying mechanisms associated with neurodegenerative diseases affecting brain morphology and behavior.

Effect of hypergravity on the mouse basal expression of NGF and BDNF in the retina, visual cortex and geniculate nucleus: correlative aspects with NPY immunoreactivity.

We investigated the effect of hypergravitation on Nerve growth factor (NGF) and Brain-derived-neurotrophic factor (BDNF) expression in the visual cortex, geniculate nucleus (GN), and retina of adult male mice. The results showed that altered gravity causes an increase in NGF and BDNF in the visual cortex and GN which resulted to be associated with an up-regulation of cells immunoreactive to neuropeptide Y (NPY) in the visual cortex and GN. We also found a decrease in NGF, BDNF, and NPY in the mouse retina exposed to hypergravity. These findings suggest that alteration in gravitational environment differentially affects local neurotrophic factors and NPY expression. The possible functional significance of these observations is discussed.