Biomedical subjects

L Aloe

Publications and source records attributed to L Aloe.

At least 109 records · Page 6Linked to original sources

PubMed1998

Cholecystokinin-8 regulation of NGF concentrations in adult mouse brain through a mechanism involving CCK(A) and CCK(B) receptors.

1. Nerve growth factor (NGF), a powerful agent for the growth, differentiation and regeneration of lesioned cells of the central and peripheral nervous systems, has in recent years been indicated as a potential therapeutic agent capable of reversing the processes of cell damage in neurodegenerative events in man. Since NGF does not cross the blood-brain barrier and central NGF administration requires invasive surgical procedures, the discovery of substances modulating in vivo NGF synthesis in the brain will be extremely useful for a possible clinical use of NGF. 2. The aim of the present study to analyse if the content of NGF in the brain of adult mice can be affected by peripheral administration of cholecystokinin-8 (CCK-8), a well known neuropeptide which has stimulant actions on neurons in the brain and promotes a variety of neurobehavioural effects both in man and rodents. 3. The dose-response and time course effects of an i.p. injection of CCK-8 on the NGF concentrations in the hippocampus, cortex, hypothalamus and pituitary of adult male mice were analysed by use of a sensitive immunoenzymatic assay for NGF. The effects of pretreatment with selective CCK(A) and CCK(B) receptor antagonists and atropine on the NGF response to CCK injection were also studied. 4. The effects of CCK-8 were dose- and time-dependent and the injection of 8 nmol kg(-1) resulted in a 3 fold increase of NGF levels in the hypothalamus and pituitary, and about a 60% increase in the hippocampus. No effects were observed in the cortex. Pretreatment with a selective CCK(A) receptor antagonist blocked the CCK-induced NGF increase in the hypothalamus and pituitary. In the hippocampus the same effect was obtained with a CCK(B) receptor antagonist. Pretreatment with atropine suppressed the CCK-induced effects on NGF levels in all the brain regions examined. 5. Our results showing that i.p. injection with CCK-8 can modulate NGF levels in the brain through a mechanism which seems, in part, to be mediated via the vagal afferents, indicate that this neuropeptide may represent a useful pharmacological approach to enhance endogenous NGF levels in neuropathologies associated with a neurotrophin deficit.

Animals↗

PubMed1998

Expression of nerve growth factor receptors on the ocular surface in healthy subjects and during manifestation of inflammatory diseases.

PURPOSE: Recent studies have suggested the involvement of nerve growth factor (NGF) in the conjunctival inflammatory process and in corneal epithelium proliferation and differentiation. To verify the hypothesis that NGF could locally modulate the inflammatory and reparative processes, the authors evaluated the expression of NGF high-affinity receptor on the ocular surface in normal and pathologic conditions. METHODS: Ten conjunctival biopsies (obtained from three healthy subjects, five patients affected by vernal keratoconjunctivitis [VKC], and two patients with cicatricial pemphigoid [CP]) and five corneal specimens obtained from the Eye Bank of Veneto (Italy) were evaluated. All specimens were histologically stained, and immunohistochemistry was performed to identify the NGF high-affinity receptor (TrkA). RESULTS: All tissues expressed immunoreactivity for NGF receptors. In conjunctival specimens of healthy subjects, basal epithelial cells strongly expressed immunoreactivity and, in the stroma, rare cells were immunopositive for TrkA. No significant difference in immunoreactivity was observed in the conjunctival epithelium between healthy subjects and patients with inflammatory conjunctival diseases, whereas there were more immunopositive cells observed in the conjunctival stroma of VKC and CP patients than in the controls. The immunoreactivity in the cornea was confined to basal epithelial cells and endothelium. CONCLUSIONS: The NGF receptor is present on the human ocular surface. The authors' data support the possibility that NGF modulates ocular inflammation and corneal epithelial proliferation and differentiation through its receptors.

Adolescent↗

PubMed1998

A role of nerve growth factor in oligodendrocyte growth and differentiation of EAE affected rats.

We have previously shown that the level of nerve growth factor (NGF) undergoes significant changes in the cerebrospinal fluid of patients with Multiple Sclerosis and in the brain of rats affected by Experimental Allergic Encephalomyelitis (EAE). The functional significance of the endogenous disregulation of NGF is not known, though recent studies seem to suggest that NGF might be associated with the ability of oligodendrocytes (OLs) to produce and/or utilise NGF. The aim of the present study was therefore to investigate whether NGF is involved in the development and differentiation of cells of the subventricular zone (SVz) which arbors undifferentiated cells that can give rise to OLs. The results show that NGF injected into the brain of developing rats and of rats affected by EAE is retrogradely transported from the SVz to the brain parenchyma. These findings suggest that during the early phase of brain development and during EAE, NGF, along with other growth factors, is implicated in growth and/or differentiation of OLs and in protecting neuronal injury. The possible functional role of NGF in these events has been discussed.

Age Factors↗

PubMed1997

TNF-alpha expressed in the brain of transgenic mice lowers central tyroxine hydroxylase immunoreactivity and alters grooming behavior.

Tumor necrosis factor-alpha (TNF-alpha) is a cytokine involved in a wide range of biological effects both in physiological and non-physiological conditions. It is also produced in the central nervous system (CNS) where it has been implicated in reparative processes after traumatic injuries and in CNS demyelination, neurodegeneration and inflammation. Using transgenic mice (Tg-m) expressing TNF-alpha specifically in the CNS, we showed that the overexpression of this cytokine reduced tyroxine hydroxylase immunoreactivity (TH-ir) in the caudate-putamen and in the dorsomedial hypothalamic areas and impaired grooming behavior. We also showed that this behavior is increased following anti-nerve growth factor injection. These findings support the hypothesis, proposed by others, that TNF-alpha is involved in the degenerative processes which occur in Parkinson's disease.

Animals↗

PubMed1997

Time-course changes of nerve growth factor, corticotropin-releasing hormone, and nitric oxide synthase isoforms and their possible role in the development of inflammatory response in experimental allergic encephalomyelitis.

In this paper we report a time-course study of development of experimental allergic encephalomyelitis in Lewis rats, by monitoring neuroendocrine regulation of the hypothalamus-pituitary-adrenal axis through corticotropin-releasing hormone mRNA expression, inflammatory cellular infiltrate, macrophagic and neuronal nitric oxide synthase, nerve growth factor (NGF), and NGF p75 and trkA receptors in the brain and spinal cord. We analyzed animals during 20 days after immunization, a time interval that corresponds to the acute immunological phase. We have described a severe, early fall of corticotropin-releasing hormone mRNA expression, which could account for the decreased response of the hypothalamus-pituitary-adrenal axis to inflammatory stress. During this period, an increase of neuronal nitric oxide synthase was observed in the cerebral cortex and spinal cord, and macrophagic nitric oxide synthase positive cells were found in the inflammatory cellular infiltrate, which was abundant in perivascular and submeningeal areas 20 days after immunization. Concomitantly, we found a dramatic up-regulation of NGF receptors on the wall of blood vessels and adjacent neurons in perivascular areas. NGF content also had increased in some brain areas, such as the thalamus, while it had decreased in others, like the spinal cord and medulla oblongata, at time points in which the most serious cellular infiltrate was found.

Adrenal Glands↗

PubMed1997

Nerve growth factor effects on the song control system of zebra finches.

The aim of this experiment was to test whether or not nerve growth factor (NGF) is involved in cholinergic processes in the avian brain, by injecting NGF into the higher vocal center (HVC) and examining its effects on adult male zebra finch song. Since NGF has been hypothesized to protect cells after injury, some birds received both NGF and ibotenic acid (IBO) lesions of HVC, while others received either NGF or IBO or neither (SHAM). Only the IBO-treated birds showed alterations in song. Although there was no evidence of cell preservation in the immunocytochemical and morphological analysis NGF appears to prevent the IBO induced impairment in song augmenting the activity of the remaining neurons and enhancing brain repair.

Animals↗

PubMed1997

High-dose anabolic androgenic steroids modulate concentrations of nerve growth factor and expression of its low affinity receptor (p75-NGFr) in male rat brain.

The effects of treatment with a high dose of nandrolone or testosterone on nerve growth factor (NGF) levels and NGF low-affinity receptor (p75-NGFr) distribution in the brain were analyzed. Nandrolone, subcutaneously injected in rats for several weeks, caused an increase of NGF levels in the hippocampus and septum and a decrease in the hypothalamus. The number of p75-NGFr-immunoreactive neurons and the p75-NGFr expression levels were reduced in the septum and vertical and horizontal Broca's bands. Testosterone injections caused an increase of NGF levels in the hippocampus, septum, and occipital cortex and induced an upregulation of p75-NGFr in the forebrain NGF target regions. This testosterone effect suggests that nandrolone and testosterone affect brain NGF target cells by a different mechanism(s). Nandrolone may interfere with NGF transport and/or utilization by forebrain neurons, causing an altered p75-NGFr expression and NGF accumulation as a consequence. Since NGF is known to maintain forebrain neurons and to regulate neurobehavioral functions, including memory, learning, and defensive behavior, it is possible to hypothesize that this neurotrophin may play a role in the mechanism of action of anabolic androgenic steroids (AAS) in the brain and be associated with endocrine and behavioral dysfunctions occurring due to AAS abuse.

Anabolic Agents↗

PubMed1997

Thyroid hormone regulates NGF content and p75LNGFR expression in the basal forebrain of adult rats.

Several lines of data from human and animal studies have suggested a role of thyroid hormone in the regulation of cholinergic neurons in the adult brain. In this study we have investigated the content of nerve growth factor (NGF) and the expression of NGF low affinity receptor (p75(LNGFR)) in the basal forebrain of adult hypothyroid rats. We describe an increase of both NGF and p75(LNGFR) expression in the basal forebrain of adult hypothyroid rats. The administration of colchicine up-regulates p75(LNGFR) expression in both hypo- and control rats, whereas it fails to down-regulate choline acetyl transferase mRNA expression during hypothyroidism. These data offer a possible neurobiological explanation to cognitive defects observed during adult hypothyroidism in humans.

Animals↗

PubMed1997

Nerve growth factor (NGF) reduces and NGF antibody exacerbates retinal damage induced in rabbit by experimental ocular hypertension.

BACKGROUND: It has been shown that intravitreal injection of NGF inhibits ganglion cell degeneration after optic nerve transection and ischemic injury. The aim of our study was to investigate the presence of NGF in aqueous humor and its involvement in retinal damage during ocular hypertension. METHODS: We used an experimental model of ocular hypertension in rabbit. Before treatment and 4, 10 and 15 days after induction of hypertension, we evaluated histological retinal damage and NGF levels in aqueous humor using an immunoenzymatic assay. Polyclonal anti-NGF antibodies were injected intravitreally into one eye of each rabbit (n = 6), and the animals were killed after 4 days of hypertension. Another group of rabbits (n = 12) was injected retro-ocularly with NGF and killed after 10 or 15 days of treatment for histologic evaluation of the retina. RESULTS: Our data show that experimental ocular hypertension in adult rabbits induces retinal damage and enhances local NGF levels. The highest NGF value was found after 4 days of intraocular hypertension: high levels persisted, though to a lesser extent, for up to 15 days. Histological examination revealed that the number of retinal ganglion cells (RGC) remained unchanged during the first 4 days but decreased at 10 days. These studies also showed that retro-ocular administration of NGF reduced RGC loss, whereas intraocular injection of NGF antibodies, which inhibited the endogenous NGF, exacerbated the retinal insult. CONCLUSION: These findings demonstrate a protective effect of NGF on RGC damaged by ocular hypertension and prompt further investigations to evaluate a possible therapeutic use of NGF to retard RGC death in humans.

Animals↗

PubMed1997

Role of TNF-alpha but not NGF in murine hyperalgesia induced by parasitic infection.

Using adult mice infected with the trematode Schistosoma mansoni, we observed that this infection induces both thermal hyperalgesia and an increase in the levels of nerve growth factor in the paws. To explore the mechanism involved in peripheral hypersensitivity during chronic infection, mice were infected with 60 cercariae of S. mansoni and injected 17 weeks later with nerve growth factor, anti-nerve growth factor or with other molecules known to be associated with hyperalgesic processes. The results of these studies showed that antibodies against tumor necrosis factor-alpha, but not against nerve growth factor, reduce thermal sensitivity in schistosome infected mice, suggesting that this cytokine but not NGF plays a crucial role in schistosome-induced thermal hyperalgesia. Treatments with anti-inflammatory drugs support this hypothesis.

Animals↗

PubMed1997

Removal of the submaxillary salivary glands and infection with the trematode Schistosoma mansoni alters exploratory behavior and pain thresholds in female mice.

In this study, CD-1 female mice, deprived of the submaxillary salivary glands, were infected with S. mansoni and their behavior was observed 15 weeks after infection, when the eggs of the parasite are present in the brain. Sialectomized infected mice showed changes in exploratory activity, sniffing, and wall-rearing in the open-field and in the black/white box, but no differences in pain sensitivity were observed on the hot plate. The present results suggest that the modifications in the behavior of sialectomized infected mice might be associated with the inability of the animals to cope with the aversive effects of the infection and, most probably, with modifications in the levels of polypeptides released into the bloodstream by the salivary glands, affecting the NGF-responsive cells of the nervous, endocrine, and immune systems.

Animals↗

PubMed1997

Human CD4+ T cell clones produce and release nerve growth factor and express high-affinity nerve growth factor receptors.

BACKGROUND: Increasing evidence shows that nerve growth factor (NGF) plays a role in the complex and fascinating linkage between the nervous and the immune systems due to its ability to modulate functions of several inflammatory cells. OBJECTIVE: To investigate NGF receptor expression and NGF production and release by human CD4+ cells clones, which have primary relevance in modulating inflammatory events through their different subsets of functional phenotypes. METHODS: The expression of NGF and a transmembrane tyrosine kinase (TrkA) was evaluated by immunohistochemistry and flow cytometry analysis in five T(H0), six T(H1), and five T(H2) cell clones derived from human circulating mononuclear blood cells. Moreover, the amount of NGF protein was assessed by measuring the NGF levels in culture supernatants of the T cell clones before stimulation and 48 hours after phytohemagglutinin (PHA) activation by use of an immunoenzymatic assay. RESULTS: Our data have shown that in unstimulated conditions, human CD4+ T cell clones express both immunoreactivity for NGF and the TrkA NGF receptor irrespective of their cytokine profile. Moreover, T(H1) and T(H2) clones, but not T(H0) clones, secrete NGF in basal conditions. PHA activation induces NGF secretion in T(H0) clones and a significant increase of NGF levels in T(H2) (p < 0.05), but not in T(H1) culture supernatants. CONCLUSIONS: Results obtained represent the first evidence of TrkA expression and NGF production and release in human CD4+ cell clones and suggest a possible functional role of NGF in modulating the immune and inflammatory network.

CD4-Positive T-Lymphocytes↗

PubMed1997

NGF content and expression in the rat pituitary gland and regulation by thyroid hormone.

The involvement of nerve growth factor (NGF) in neuroendocrine regulation is supported by several lines of evidence. In this paper, we investigated the NGF content and expression in the pituitary gland and other endocrine organs during dysendocrine states (thyroidectomized, adrenalectomized and gonadectomized male rats). We found an increase of NGF-IR in the pituitary gland and testis of hypothyroid rats whereas no differences were found in the adrenal gland and blood. Also, NGF mRNA expression had increased in the anterior pituitary of hypothyroid rats whereas it had not changed after adrenalectomy and gonadectomy. Moreover, other neurotrophins and neurotrophin high-affinity receptors were unchanged in the anterior pituitary of hypothyroid rats. These data indicate that pituitary NGF is selectively modulated by thyroid status of the animal, further supporting a close link between NGF and thyroid hormone.

Adrenal Glands↗

PubMed1997

Postnatal NGF administration causes adult hyperalgesia and overreactivity to social stimuli but does not reverse capsaicin induced hypoalgesia.

The present longitudinal analysis was aimed at assessing (i) the effects of developmental capsaicin (CAPS) administration on nociceptive responsivity and on the response of adult mice to social stimuli; (ii) the action of NGF on the ontogeny of the same nociceptive response and social stimuli; (iii) whether capsaicin treatment could be reversed by subsequent treatment with NGF. CD-1 mouse pups were treated with either capsaicin (50 mg/kg, s.c.) or vehicle on postnatal days (PNDs) 5 and 8. Every other day from PND 9 to PND 21 the same pups received a daily injection of NGF (0.75 mg/kg, s.c.). During both the prepuberal stage (PNDs 14, 21, and 28) and adulthood, mice were repeatedly tested in a hot-plate apparatus (52 +/- 0.1 degrees C for 1 min). At adulthood they also underwent an aggressive behaviour test. NGF-treated mice showed a shorter latency to hindlimb licking response in the hot plate compared to both controls and NGF-CAPS groups. CAPS-treated subjects showed a long-lasting hypoalgesia at both prepuberal and adult stages that was not modified by subsequent NGF treatment. Finally, NGF-treated mice were more aggressive than both controls and CAPS-NGF animals.

Aggression↗

PubMed1997

Thyroid hormone-induced plasticity in the adult rat brain.

It is well known that thyroid hormone plays a crucial role in the development and maturation of the nervous system. However, little is known about the role of thyroid hormone in the adult brain. In this short review we have dwelt on this point, with regard to the role of thyroid hormone on neuropeptide gene expression regulation in the paraventricular nucleus of the hypothalamus and in extrahypothalamic brain areas, on neurotrophin and neurotrophin receptor expression in the hippocampus and basal forebrain in basal conditions, and after neurotoxic challenges. Effects of hypothyroidism are discussed in view of a possible role of thyroid status in brain aging quality.

Animals↗

PubMed1997

The expanding role of nerve growth factor: from neurotrophic activity to immunologic diseases.

Numerous studies published in the last 10-15 years have shown that nerve growth factor (NGF), a polypeptide originally discovered in connection with its neurotrophic activity, also acts on cells of the immune system. NGF has been found in various immune organs including the spleen, lymph nodes, and thymus, and cells such as mast cells, eosinophils, and B and T cells. The circulating levels of NGF increase in inflammatory responses, in various autoimmune diseases, in parasitic infections, and in allergic diseases. Stress-related events both in animal models and in man also result in an increase of NGF, suggesting that this molecule is involved in neuroendocrine functions. The rapid release of NGF is part of an alerting signal in response to either psychologically stressful or anxiogenic conditions in response to homeostatic alteration. Thus, the inflammation and stress-induced increase in NGF might alone or in association with other biologic mediators induce the activation of immune cells during immunologic insults. A clearer understanding of the role of NGF in these events may be useful to identify the mechanisms implicated in certain neuroimmune and immune dysfunctions.

Communicable Diseases↗

PubMed1997

Haloperidol administration in humans lowers plasma nerve growth factor level: evidence that sedation induces opposite effects to arousal.

Studies reported in recent years have indicated that the level of nerve growth factor (NGF), in both the brain and in the bloodstream, increases following stressful events and anxiety-associated behaviour. These observations prompted us to investigate whether an anti-arousal drug would induce an opposite effect. We have reported that the administration of haloperidol (HA), a neuroleptic drug clinically used for psychiatric disorders, decreases NGF levels in the hypothalamus of adult male mice. In the present study, we showed that HA reduced the basal NGF plasma levels in 8 neuroleptic-free schizophrenic patients. These observations strengthen the hypothesis that NGF may play a functional role in stress-coping responses.

Adolescent↗

PubMed1997

Increased plasma levels of substance P in vernal keratoconjunctivitis.

PURPOSE: The increase of nerve growth factor (NGF) plasma levels in vernal keratoconjunctivitis (VKC) patients has been demonstrated previously. Results of numerous studies in vitro and in vivo have shown that NGF modulates the synthesis of substance P (SP), a neuropeptide involved in the pathogenesis of human allergic diseases. In this study the involvement of SP in this allergic conjunctivitis is investigated, along with its relationship with NGF and other systemic and local markers of VKC. METHODS: Competitive radioimmunoassays were used to detect the levels of SP in plasma, the levels of eosinophil cationic protein, and the total and specific immunoglobulin E in the serum of 11 patients with VKC and in 11 healthy matched controls. Plasma levels of nerve growth factor (NGF) were measured in all VKC patients and controls using an immunoenzymatic assay. Histologic evaluation was performed in tarsal and bulbar conjunctival specimens obtained in biopsies from 8 VKC patients and 4 control subjects. RESULTS: Patients with VKC show a significant increase of SP and NGF plasma levels (P < 0.003 and P < 0.001, respectively), and an increase of eosinophil cationic protein and immunoglobulin E levels in the serum (P < 0.001 and P < 0.002, respectively). Mast cells, eosinophils, and lymphocytes were also significantly increased in the conjunctiva of VKC patients. Interestingly enough, VKC patients with the highest NGF plasma levels also showed the highest SP levels. CONCLUSIONS: The data show the involvement of SP in VKC and suggest that SP with NGF could modulate the allergic response in this disease, probably through an interaction with inflammatory cytokines.

Adolescent↗