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We investigated immunoreactivity for p75 neurotrophin receptor (NTR) in the spinal cord white matter and septum of rats made cobalamin-deficient (Cbl-D) by means of total gastrectomy or a Cbl-D diet. Cbl deficiency down-regulates p75NTR-immunoreactive cell levels in spinal cord white matter and septum with different time courses. On the whole, the spinal cord white matter seems to be more affected in terms of p75NTR-immunoreactive cells, most of which are astrocytes. The p75NTR-immunoreactive cell levels in the spinal cord white matter and septum normalized in rats treated with Cbl (scheme b) and killed 4 months after total gastrectomy. However, Western blot analysis of p75NTR in the spinal cords of Cbl-D rats shows increased p75NTR protein levels, which are resistant to Cbl replacement. These findings demonstrate that a neurotrophic vitamin (Cbl) positively regulates the levels of a neurotrophic receptor (p75NTR) (at least in terms of immunohistochemistry) in rat central nervous system, although the underlying mechanism(s) are still unknown.

It has been shown that conjunctivally applied NGF in rats can reach the retina and optic nerve. Whether topical eye NGF application reaches the central nervous system is not known. In the present study, we have addressed this question. It was found that topical eye NGF application affects brain cells. Time-course studies revealed that repeated NGF application leads to high concentration of this neurotrophins after 6 h and normal levels after 24 h. Our results also showed that topical eye application of NGF causes an enhanced expression of NGF receptors and ChAT immunoreactivity in forebrain cholinergic neurons, suggesting that ocular NGF application could have a functional role on damaged brain cells. The present findings suggest that eye NGF application can represent an alternative route to prevent degeneration of NGF-receptive neurons involved in disorders such as Alzheimer and Parkinson.

The aim of this study was to investigate the effect of electroacupuncture (EA) on the progression of retinal degeneration in rats affected by inherited retinitis pigmentosa (IRP) and to correlate this event with the retinal expression of neurotrophins. Thirty-day-old Royal College of Surgeons (RCS) rats were exposed to 25-min-long daily sessions of low-frequency EA for 11 consecutive days. Control-untreated and EA-treated rats were sacrificed 1 h after the last EA session, and their retina removed for biochemical, molecular, and immunohistochemical analyses. Our data revealed that daily sessions of low-frequency EA for 11 days to RCS rats during a critical developmental stage of retinal cell degeneration cause an increase of retinal nerve growth factor (NGF) and NGF high-affinity receptor (TrkA) expression; and increase of outer nuclear layer (ONL) thickness; and enhanced vascularization. These findings suggest the possible beneficial effects of EA treatment in the development of IRP-like retinal degeneration of RCS rats and that the mechanism through which EA might exerts its action on the regulation of NGF and brain-derived neurotrophic factor (BDNF) and/or their receptors in retinal cells.

The role of nitric oxide (NO) in inflammatory/demyelinating diseases is undergoing extensive investigation as a potential target for therapeutic intervention. However, interference with NO production has resulted in contrasting effects on the development of experimental allergic encephalomyelitis (EAE), the most widely used experimental model for multiple sclerosis (MS). Purpose of this paper was both the analysis of the individual clinical evolution of EAE induced in Lewis female rats by active immunisation and the evaluation of the effect of treatment with aminoguanidine, a selective inhibitor for the inducible isoform of nitric oxide synthase (iNOS). In our experimental model, relapse occurred in 66% of animals. Aminoguanidine treatment, started 3 days before immunisation, guaranteed a complete recovery from the acute phase and a delayed, milder relapse. Moreover, 79 days after immunisation inflammatory cellular infiltrates in the spinal cord were reduced. These data further support the involvement of NO in EAE evolution.

In this study we used two lines of transgenic mice overexpressing tumor necrosis factor alpha (TNF-alpha) in the central nervous system (CNS), one characterized by reactive gliosis, inflammatory demyelination and neurological deficits (Tg6074) the other showing no neurological or phenotypical alterations (TgK3) to investigate the effect of TNF-alpha on brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels and learning abilities. The results showed that the amount of NGF in the brain of Tg6074 and TgK3 transgenic mice is low in the hippocampus and in the spinal cord, increases in the hypothalamus of Tg6074 and showed no significant changes in the cortex. BDNF levels were low in the hippocampus and spinal cord of TgK3. BDNF increased in the hypothalamus of TgK3 and Tg6074 while in the cortex, BDNF increased only in Tg6074 mice. Transgenic mice also had memory impairments as revealed by the Morris Water Maze test. These findings indicate that TNF-alpha significantly influences BDNF and NGF synthesis, most probably in a dose-dependent manner. Learning abilities were also differently affected by overexpression of TNF-alpha, but were not associated with inflammatory activity. The possible functional implications of our findings are discussed.

Twenty-one-day-old mice show a characteristic enhancement of locomotor activity upon injection of the cholinergic (muscarinic) blocking drug scopolamine. Intracerebral (third ventricle) injection of nerve growth factor (NGF) 24 h prior to scopolamine injection significantly enhances the drug-induced hyperactivity without modifying baseline activity. Such potentiation of the scopolamine effect was not obtained in 10-week-old mice treated and tested similarly.

The injection of a drug endowed with the property of stimulating alpha-adrenergic receptors, cyclocytidine (Cyclo-C), produces drastic depletion of NGF from the granular convoluted tubules (GCT) of the mouse submaxillary salivary gland and a marked NGF level increase in the bloodstream. The NGF discharged from the gland gains access to the blood. Histological studies, immunohistochemistry, in vitro biological assays and radioimmunoassays gave evidence for the growth response elicited by the endogenously released salivary NGF in intact and surgically axotomized sympathetic ganglia. These results suggest that the mouse salivary NGF displays a biological activity on its target sympathetic nerve cells.

When NGF is orally administered to neonatal mice at the daily doses of 10 micrograms/animal for a 1-week period, a marked volume increase of para- and prevertebral sympathetic ganglia and neuronal hypertrophy are produced. Conversely oral administration of NGF antiserum to NGF for the same length of time, produces destruction of sympathetic nerve cells. The NGF effects correlate with the appearance in blood of this molecule in a biologically active form.