Nerve growth factor restores the expression of vasopressin and vasoactive intestinal polypeptide in the suprachiasmatic nucleus of aged rats.
ABSTRACT Aging leads to a decrease in the number of neurons expressing vasopressin (VP) and vasoactive intestinal polypeptide (VIP) in the suprachiasmatic nucleus (SCN) of the rat. Similar results were observed following prolonged alcohol consumption and withdrawal. In the latter circumstances, the administration of nerve growth factor (NGF) restored the synthesis and expression of those neuropeptides despite the absence of TrkA receptors in SCN neurons. Thus, we decided to test whether the administration of NGF would improve the expression of neuropeptides in the SCN of aged rats. For this purpose, NGF was delivered intraventricularly to aged rats over a period of 14 days. The somatic volume and the total number of VP- and VIP-immunostained SCN neurons were estimated by applying stereological methods. No age-related variations were found regarding the volume of the neuronal cell bodies. Yet, a striking reduction in the number of VP- and VIP-immunoreactive neurons was detected in aged animals and found to be completely retrieved by NGF. This finding shows that exogenous NGF administered to aged rats restores the neurochemical phenotype of the SCN. This might occur either through direct signaling of SCN neurons via p75NTR or through enhancement of the cholinergic input to the SCN.
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ABSTRACT: During a critical period of postnatal development, the temporary closure of one eye in kittens will permanently shift the ocular dominance (OD) of neurones in the striate cortex to the eye that remains open. The OD plasticity can be substantially reduced if the cortex is infused continuously with the catecholamine neurotoxin 6-hydroxydopamine (6-OHDA) during the period of monocular deprivation, an effect that has been attributed to selective depletion of cortical noradrenaline. However, several other methods causing noradrenaline (NA) depletion leave the plasticity intact. Here we present a possible explanation for the conflicting results. Combined destruction of the cortical noradrenergic and cholinergic innervations reduces the physiological response to monocular deprivation although lesions of either system alone are ineffective. We also find that 6-OHDA can interfere directly with the action of acetylcholine (ACh) on cortical neurones. Taken together, our results suggest that intracortical 6-OHDA disrupts plasticity by interfering with both cholinergic and noradrenergic transmission and raise the possibility that ACh and NA facilitate synaptic modifications in the striate cortex by a common molecular mechanism.Nature 01/1986; 320(6058):172-6. · 38.60 Impact Factor
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ABSTRACT: Aged rats, displaying impairments in spatial learning and memory associated with marked cellular atrophy of forebrain cholinergic neurons, received intracerebroventricular infusions of one of the four neurotrophins nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), or neurotrophin 4/5 (NT-4/5), or a combination of NGF and BDNF, or vehicle. During the 4-week infusion period rats receiving NGF, NT-3, or NT-4/5 showed improved acquisition and retention of spatial memory. With NGF and NT-3, but not NT-4/5, this was accompanied by a significant reduction in cholinergic neuron atrophy in septum, nucleus basalis, and striatum. BDNF, in contrast, was without effect either alone or in combination with NGF. These results show that memory deficits associated with aging can be reversed by several members of the neurotrophin family and that this effect may be mediated through activation of multiple neurotrophin receptors associated with cholinergic and possibly noncholinergic systems in the brain.Proceedings of the National Academy of Sciences 09/1994; 91(18):8607-11. · 9.74 Impact Factor
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ABSTRACT: [125I]alpha-Bungarotoxin (alpha-Btx) binding was quantified in autoradiographs of in vitro labeled sections through the rat suprachiasmatic nucleus (SCN). Recent evidence suggests that acetylcholine and alpha-Btx binding sites in the SCN region may mediate effects of light on circadian functions. In contrast to the ventrolateral termination of retinal axons, there was a consistent pattern of relatively high alpha-Btx binding levels in the dorsolateral SCN and low levels in the ventromedial SCN. In addition, enucleation had little or no effect. We also investigated the possibility that phase-dependent influences of light on circadian functions could reflect the presence of light-induced or daily rhythms in alpha-Btx binding. Animals were tested in a light-dark cycle or after 1-2 days in constant light. The dorsolateral SCN showed a small but significant decline of alpha-Btx binding in animals in light at night compared to darkness at night. alpha-Btx binding in the SCN showed no statistically significant daily variation in animals in the light-dark cycle.Brain Research 04/1987; 407(1):9-16. · 2.88 Impact Factor