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Strong evidence showed neurotoxic properties of beta amyloid (Aβ) and its pivotal role in the Alzheimer's disease (AD) pathogenesis. Beside, experimental data suggest that Aβ may have physiological roles considering that such soluble peptide is produced and secreted during normal cellular activity. There is now suggestive evidence that neurodegenerative conditions, like AD, involve nitric oxide (NO) in their pathogenesis. Nitric oxide also possess potent neuromodulatory actions in brain regions, such as prefrontal cortex (PFC), hippocampus (HIPP), and nucleus accumbens (NAC). In the present study, we evaluated the effect of acute Aβ injection on norepinephrine (NE) content before and after pharmacological manipulations of nitrergic system in above mentioned areas. Moreover, effects of the peptide on NOS activity were evaluated. Our data showed that 2 h after i.c.v. soluble Aβ administration, NE concentrations were significantly increased in the considered areas along with increased iNOS activity. Pre-treatment with NOS inhibitors, 7-Nitroindazole (7-NI), and N6-(1-iminoethyl)-L-lysine-dihydrochloride (L-NIL), reversed Aβ-induced changes. Ultimately, pharmacological block of interleukin1 (IL-1) receptors prevented NE increase in all brain regions. Taken together our findings suggest that NO and IL-1 are critically involved in regional noradrenergic alterations induced by soluble Aβ injection.

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Graphical abstractRaman microspectroscopy and Atomic Force Microscopy can successfully discriminate two cellular types of cells characterized by different degree of oral squamous cell carcinoma. The discrimination by Raman microspectroscopy occurs according to a larger content of nucleic acids and minor content of protein component in cells characterized by a larger degree of disease, whereas the discrimination by Atomic Force Microscopy is achieved because of a decrease of stiffness as the degree of disease increase. AbstractOral squamous cell carcinoma is a widespread cancer disease whose survival rate is strongly dependent on early diagnosis and on the degree of the malignancy. The conventional histopathology methods, which are currently the standard ones for diagnosis, are very invasive so that they can be hardly proposed as screening methods for an early and accurate detection of disease. Raman microspectroscopy and Atomic Force Microscopy can be potentially considered useful tools for cancer diagnosis and detection of the malignancy degree because they provide information about biochemical cellular content and nanomechanical properties, respectively, which would be modified by the onset and progression of pathology. The present work shows that both such techniques can successfully discriminate the two cellular types of cells characterized by different degree of oral squamous cell carcinoma. The discrimination by Raman microspectroscopy occurs according to a larger content of nucleic acids and minor content of protein component in cells characterized by a larger degree of disease, whereas the discrimination by Atomic Force Microscopy is achieved because of a decrease of stiffness as the degree of disease increase. Overall, both techniques could provide useful diagnostic information related to the degree of malignancy of the oral squamous cell carcinoma disease.

Raman micro-spectroscopy can be used to investigate biological single cells exposed to different chemicals. Since chronic exposure at low doses of pesticides can promote several diseases, the investigation of cellular changes induced by exposure to non-cytotoxic doses of pesticides is of increasing interest. The efficiency of Raman micro-spectroscopy to detect chemical modification in normal human keratinocytes induced by exposure to non-cytotoxic doses of chlorpyriphos, an organophosphate pesticide present in many plant-protection products, was investigated. Such modification affects mainly proteineous components (both single amino acids and amide linkages between amino acids) of the nucleus, cellular membranes and cytoplasm as well as the nucleic acid component of the nucleus. Chemical modifications are already detectable after 24 h exposure of keratinocytes at a chlorpyriphos concentration of 10 −6 M, which is three orders of magnitude lower than the cytotoxic concentration (10 −3 M). Heavy damage to the lipid component occurs after exposure to the nearly cytotoxic concentration (10 −4 M). Atomic force microscopy images of keratinocyte cells exposed for 24 h to various chlorpyriphos concentrations show a progressive deterioration of the morphology of cellular membrane as the chlorpyriphos concentration increases. The results of this work may have wide applications in the monitoring of molecular changes in single human cells exposed to toxic agents.