Brainstem cholinergic populations survive in neurodegenerative disease, while basal forebrain cholinergic neurons degenerate. We have postulated that variable resistance to oxidative stress may in part explain this. Rat primary cultures were used to study the effects of several nitrosative/oxidative stressors on brainstem (upper pons, containing pedunculopontine and lateraldorsal tegmental nuclei; BS) cholinergic neurons, comparing them with medial septal (MS), and striatal cholinergic neurons. BS cholinergic neurons were significantly more resistant to S-nitro-N-acetyl-d,l-penicillamine (SNAP), sodium nitroprusside (SNP), and hydrogen peroxide than were MS cholinergic neurons, which in turn were more resistant than striatal cholinergic neurons. Pharmacological analyses using specific inhibitors of neuroprotective systems also revealed differences between these three cholinergic populations with respect to their vulnerability to SNAP. Toxicity of SNAP to BS neurons was exacerbated by blocking NF-kappaB activation with SN50 or ERK1/2 activation by PD98059, or by inhibition of phosphoinositide-3 kinase (PI3K) activity by LY294002. In contrast, SNAP toxicity to MS neurons was augmented only by SN50, and SNAP toxicity to striatal cholinergic neurons was not increased by any of these three pharmacological agents. In neuron-enriched primary cultures, BS cholinergic neurons remained resistant to SNAP while MS cholinergic neurons remained vulnerable to this agent. Immunohistochemical experiments demonstrated nitric oxide (NO)-induced increases in nuclear levels of phospho-epitopes for ERK1/2 and Akt, and of the p65 subunit of NF-kappaB, within BS cholinergic neurons. These data indicate that the relative resistance of BS cholinergic neurons to toxic levels of nitric oxide involves three intrinsic neuroprotective pathways that control transcriptional and anti-apoptotic cellular functions.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2003.12.021DOI Listing

Publication Analysis

Top Keywords

cholinergic neurons
48
neurons
14
cholinergic
13
striatal cholinergic
12
snap toxicity
12
cholinergic populations
8
primary cultures
8
neurons remained
8
nitric oxide
8
snap
6

Similar Publications

Few of the many chemicals that regulatory agencies are charged with assessing for risk have been carefully tested for developmental neurotoxicity (DNT). To speed up testing efforts, as well as to reduce the use of vertebrate animals, great effort is being devoted to alternate laboratory models for testing DNT. A major mechanism of DNT is altered neuronal architecture resulting from chemical exposure during neurodevelopment.

View Article and Find Full Text PDF

The brain faces the challenging task of preserving a consistent portrayal of the external world in the face of disruptive sensory inputs. What alterations occur in sensory representation amidst noise, and how does brain activity adapt to it? Although it has previously been shown that background white noise (WN) decreases responses to salient sounds, a mechanistic understanding of the brain processes responsible for such changes is lacking. We investigated the effect of background WN on neuronal spiking activity, membrane potential, and network oscillations in the mouse central auditory system.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is a neurodegenerative condition characterized by a gradual decline in cognitive function, for which few effective treatments exist. This study investigated the neuroprotective potential of root extract and its key constituents (baicalein, chrysin, oroxylin A) against AD hallmarks. The extract and its constituents exhibited antioxidant activity in the DPPH assay.

View Article and Find Full Text PDF

Astrocytes help protect neurons from potential damage caused by reactive oxygen species (ROS). While ROS can also exert beneficial effects, it remains unknown how neuronal ROS signalling is activated during memory formation, and whether astrocytes play a role in this process. Here we discover an astrocyte-to-neuron HO signalling cascade in Drosophila that is essential for long-term memory formation.

View Article and Find Full Text PDF

Cognitive impairment is considered to be one of the key features of Parkinson's disease (PD), ultimately resulting in PD-related dementia in approximately 80% of patients over the course of the disease. Several distinct cognitive syndromes of PD have been suggested, driven by different neurotransmitter deficiencies and thus requiring different treatment regimes. In this study, we aimed to identify characteristic brain covariance patterns that reveal how cholinergic denervation is related to PD and to cognitive impairment, focusing on four domains, including attention, executive functioning, memory, and visuospatial cognition.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!