Leong CS, Maness EB, Baraki DI, Burk JA (2016) Effects of protein kinase C activation on attention deficits following loss of corticopetal cholinergic neurons. Neuroscience 2016 Abstracts 833.03 / HHH22 . Society for Neuroscience, San Diego, CA.
Summary: Alzheimer’s disease (AD) is a neurodegenerative dementia characterized by memory loss, cognitive impairment, and attention deficits. Damage to corticopetal cholinergic neurons originating in the basal forebrain is thought to contribute to the attention deficits. Recent evidence had identified G-protein decoupling at the M1 muscarinic acetylcholine receptor as well as decreased levels of protein kinase C (PKC) in rat AD models and the human AD brain. PKC is a signaling kinase that can affect neurite outgrowth, synaptic formation, and neurotransmitter release. PKC activation additionally may affect voltage-gated calcium currents. Previous research in this lab has shown that inhibition of PKC by chelerythrine chloride decreased signal detection in a sustained attention task. The present experiment evaluates the effect of PKC activation on sustained attention following loss of cortical cholinergic projections induced by infusions of 192 IgG-saporin into the basal forebrain. Male and female Sprague-Dawley rats were trained to discriminate between signals (illumination of a central panel light) and nonsignals (no panel light illumination) in a two-lever sustained attention task. Each rat received intraventricular infusions of the PKC activator bryostatin-1 (0, 0.5, 2.0, and 4.0pM) prior to testing. In the middle block of trials, a flashing houselight distracter was included to increase attentional demands. Compared to sham-lesioned animals, lesioned animals showed poorer signal detection in the distracter block of the task, but no differential effects of lesion on nonsignal trials. Distracter scores (initial block of trials with no distracter – distracter block) were calculated for each behavioral measure. For signal detection, there was a dose × group interaction (F(3,30) = 3.069, p = 0.043). Bryostatin-1 attenuated signal detection deficits in lesioned animals. Sham-treated animals showed decreased performance with increased bryostatin-1 dosage. Following the highest bryostatin-1 dose, there were no difference in signal detection between the sham and lesioned animals. The present results support the hypothesis that Bryostatin-1 can improve performance in a visual attention task following damage to corticopetal cholinergic neurons.
Related Products: 192-IgG-SAP (Cat. #IT-01)