ABSTRACT
Title
Involvement of nitric oxide in noradrenergic alteration induced by acute soluble beta amyloid
Authors
M. Colaianna1, L. Ciuffreda1, L. Trabace1 and V. Cuomo2
1Dept. of Biomedical Sciences, School of Medicine, University of Foggia, Italy
2 Dept. of Human Physiology and Pharmacology Vittorio Erspamer, University of Rome, La Sapienza, Italy
1Dept. of Biomedical Sciences, School of Medicine, University of Foggia, Italy
2 Dept. of Human Physiology and Pharmacology Vittorio Erspamer, University of Rome, La Sapienza, Italy
Abstract
Strong scientific evidences have shown the neurotoxic properties of beta amyloid (BA) and its pivotal role in the pathogenesis of AD (Hardy and Selkoe, 2002). Experimental data (Mura et al, 2010) do suggest that BA, besides its unquestioned neurotoxic activity, may have physiological roles consistent with the fact that the peptide, in its soluble form, is produced and secreted during normal cellular activity. Noteworthy BA has been shown to modulate synaptic activity in absence of neurotoxicity (Kamenetz et al, 2003).
On the other hand, there is now suggestive evidence that neurodegenerative conditions such as AD involve nitric oxide (NO) in their pathogenesis (Guix et al., 2005). Remarkably, NO also possess potent neuromodulatory actions in several brain regions, such as prefrontal cortex (PFC), hippocampus (HIPP) and nucleus accumbens (NAC) (Trabace et al, 2007; Bèchade et al, 2011; Saulskaya et al, 2010). Therefore, in the present study, we evaluated the effect of an acute BA injection on monoamine content before and after pharmacological manipulations of nitrergic system in the above mentioned areas. Our data showed that 2 hours after i.c.v. soluble BA administration, noradrenaline (NA) content was significantly increased in all areas considered (unpaired t-test, P<0.05). Interestingly, pre-treatment with a potent NO-donor, SNAP (1 mg/Kg, i.p.) completely reversed this alteration. These data were confirmed by using a NO-precursor, L-Arginine (L-Arg, 300 mg/Kg i.p.), with the exception of NAC. In fact, only in this area, co-administration of L-Arg was not able to reverse BA effect. Moreover, neither BA treatment nor nitrergic modulation affected dopaminergic system. 5-HT hippocampal concentrations resulted lowered only by SNAP pre-treatment, while BA alone or L-Arg co-administration did not induce any alterations.
Taken together, our data suggest that noradrenergic system is sensitive to acute BA administration and, in addition we evidenced that the increase in NO concentration may possibly help to prevent such neurochemical alteration. This latter data results particularly interesting since it has been reported that elevated endogenous cerebral NA may represent an etiological factor in some cases of AD; therefore the enhancement of nitrergic transmission may provide a new target and new treatment options in the early phase of the disease.
Hardy and Selkoe. (2002). Science. 297, 353-356.
Mura et al. (2010). Curr Pharm Des. 16, 672-683.
Kamenetz et al. (2003). Neuron. 37, 925-37.
Guix et al. (2005). Prog Neurobiol. 76, 126-152.
Trabace et al. (2007). Neuroscience. 147, 652-663.
Bèchade et al. (2011). Mol Cell Neurosci. 46, 762-769.
Saulskaya et al. (2010). Neurosci Behav Physiol. 40, 907-912.
On the other hand, there is now suggestive evidence that neurodegenerative conditions such as AD involve nitric oxide (NO) in their pathogenesis (Guix et al., 2005). Remarkably, NO also possess potent neuromodulatory actions in several brain regions, such as prefrontal cortex (PFC), hippocampus (HIPP) and nucleus accumbens (NAC) (Trabace et al, 2007; Bèchade et al, 2011; Saulskaya et al, 2010). Therefore, in the present study, we evaluated the effect of an acute BA injection on monoamine content before and after pharmacological manipulations of nitrergic system in the above mentioned areas. Our data showed that 2 hours after i.c.v. soluble BA administration, noradrenaline (NA) content was significantly increased in all areas considered (unpaired t-test, P<0.05). Interestingly, pre-treatment with a potent NO-donor, SNAP (1 mg/Kg, i.p.) completely reversed this alteration. These data were confirmed by using a NO-precursor, L-Arginine (L-Arg, 300 mg/Kg i.p.), with the exception of NAC. In fact, only in this area, co-administration of L-Arg was not able to reverse BA effect. Moreover, neither BA treatment nor nitrergic modulation affected dopaminergic system. 5-HT hippocampal concentrations resulted lowered only by SNAP pre-treatment, while BA alone or L-Arg co-administration did not induce any alterations.
Taken together, our data suggest that noradrenergic system is sensitive to acute BA administration and, in addition we evidenced that the increase in NO concentration may possibly help to prevent such neurochemical alteration. This latter data results particularly interesting since it has been reported that elevated endogenous cerebral NA may represent an etiological factor in some cases of AD; therefore the enhancement of nitrergic transmission may provide a new target and new treatment options in the early phase of the disease.
Hardy and Selkoe. (2002). Science. 297, 353-356.
Mura et al. (2010). Curr Pharm Des. 16, 672-683.
Kamenetz et al. (2003). Neuron. 37, 925-37.
Guix et al. (2005). Prog Neurobiol. 76, 126-152.
Trabace et al. (2007). Neuroscience. 147, 652-663.
Bèchade et al. (2011). Mol Cell Neurosci. 46, 762-769.
Saulskaya et al. (2010). Neurosci Behav Physiol. 40, 907-912.