- Home
- Knowledge Base
- References
Medial septal cholinergic neurons modulate isoflurane anesthesia.
Tai SK, Ma J, Leung LS (2014) Medial septal cholinergic neurons modulate isoflurane anesthesia. Anesthesiology 120(2):392-402. doi: 10.1097/ALN.0b013e3182a7cab6
Summary: General anesthesia is associated with a decrease in cholinergic function. This work examines the effect of volatile anesthetics such as isoflurane or ketamine in the context of cholinergic depletion. Rats received 105-ng bilateral injections of 192-IgG-SAP (Cat. #IT-01) into the medial septum. Anesthetic effects were evaluated using a loss of righting reflex test. There was no difference between lesioned and control groups in the response to ketamine. When treated with isoflurane, lesioned animals were affected for longer periods of time, and hippocampal response was reduced. The results suggest a role for septal cholinergic neurons in the sensitivity to isoflurane.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Selective potentiation of (alpha4)3(beta2)2 nicotinic acetylcholine receptors augments amplitudes of prefrontal acetylcholine- and nicotine-evoked glutamatergic transients in rats.
Grupe M, Paolone G, Jensen AA, Sandager-Nielsen K, Sarter M, Grunnet M (2013) Selective potentiation of (alpha4)3(beta2)2 nicotinic acetylcholine receptors augments amplitudes of prefrontal acetylcholine- and nicotine-evoked glutamatergic transients in rats. Biochem Pharmacol 86(10):1487-1496. doi: 10.1016/j.bcp.2013.09.005
Summary: Nicotinic acetylcholine receptors (nAChR) are involved in a wide range of processes in the central nervous system, many having to do with higher cognitive functions. In order to better understand how these receptors mediate attentional performance, the authors investigated glutamate release under varying conditions. In one series of experiments rats received a 160-ng injection of 192-IgG-SAP (Cat. #IT-01) into the right medial prefrontal cortex. The resulting decrease in glutamate release after the cholinergic lesion adds to the data indicating that positive modulation of nAChR may help alleviate attentional impairments caused by some brain disorders.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Activation of NF-κB signaling in the hippocampus without cholinergic input was aggravated by chronic stress
Lee S-Y, Kim M-S, Han J-S (2013) Activation of NF-κB signaling in the hippocampus without cholinergic input was aggravated by chronic stress. Neuroscience 2013 Abstracts 717.18. Society for Neuroscience, San Diego, CA.
Summary: Previous studies have demonstrated that loss of cholinergic input to hippocampus contributes dysfunction of HPA axis and alters GR-PKA-NF-κB signaling in hippocampus. In the hippocampus without cholinergic input, interactions of GR and PKA are decreased, whereas interactions of PKA and NF-κB are increased and phosphorylations on Ser276 of NF-κB p65 are increased. On the other hand, activation of NF-κB p65 is associated with behavioral action of stress and depression. The present research was conducted to examine whether NF-κB activation induced by cholinergic lesions is aggravated in response to chronic stress. Young adult rats received immunotoxic lesions of basal forebrain cholinergic neurons by intracranial injections of 192 IgG-saporin into the medial septum/vertical limb of the diagonal band and substantia innominata/nucleus basalis. After 2 weeks recovery from surgery, rats with cholinergic lesions and vehicle-injected control rats were subjected to 1 hr restraint stress per day for 2 weeks. We examined that cholinergic deafferentation induced alterations in GR and NF-κB p65 expression in hippocampus and prefrontal cortex. Rats with cholinergic deafferentation and chronic stress showed more activation of NF-κB p65 signaling in the hippocampus compared with rats with cholinergic deafferentation only. Thus the loss of cholinergic integrity during aging and in AD might increase proneness to chronic stress.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Assessment of the contributions of baseline performance and prefrontal cortical cholinergic projections to orexin A-induced attentional enhancement.
Zajo KN, Fadel JR, Burk JA (2013) Assessment of the contributions of baseline performance and prefrontal cortical cholinergic projections to orexin A-induced attentional enhancement. Neuroscience 2013 Abstracts 854.02. Society for Neuroscience, San Diego, CA.
Summary: Orexinergic neurons innervate several brain regions including the basal forebrain, a structure known to be crucial for normal attentional performance in rats. Our previous research demonstrated that orexin receptor blockade impairs attention and that infusions of orexin A into the lateral ventricle enhance attentional performance in animals that have just reached criteria for stable performance levels on a sustained attention task. Our current research investigated whether more highly trained animals show orexin A-induced enhancement of attentional performance and whether basal forebrain cholinergic inputs to the medial prefrontal cortex were necessary for orexin A-induced attentional enhancement. Male FBNF1 hybrid rats were trained in a sustained attention task that required discrimination of visual signals (500, 100 or 25-ms illumination of a central panel light) from trials when no signal was presented. After stable performance levels were established, rats received both intraventricular guide cannula implantation and infusions of either the immunotoxin 192IgG-saporin or vehicle into the medial prefrontal cortex. Postsurgically, rats were retrained to stable performance levels and then received infusions of 0 (vehicle), 10, 100 or 1000pM orexin A in a counterbalanced order prior to task performance. On infusion days, rats were exposed to a version of the task which increased attentional demands by presenting a visual distracter during the middle block of trials within a testing session. In rats trained to higher performance levels, intraventricular orexin A infusions did not significantly enhance attentional performance. Loss of cholinergic projections to the medial prefrontal cortex decreased attentional performance, particularly when a visual distracter was presented. Attentional performance was unaffected in lesioned rats when orexin A was infused into the lateral ventricle. Our findings suggest that orexin A-induced attentional enhancement may be dependent upon baseline performance levels and possibly the integrity of the basal forebrain cholinergic projections to the medial prefrontal cortex.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Increased hippocampal neurogenesis and prolonged amelioration of memory deficits by chronic oxotremorine treatment in a rodent model of Alzheimer’s disease.
Nair DV, Al-Badri MM, Rogido M, Pacheco-Quinto J, Peng H, Iacono D, Eckman CB, Eckman EA (2013) Increased hippocampal neurogenesis and prolonged amelioration of memory deficits by chronic oxotremorine treatment in a rodent model of Alzheimer’s disease. Neuroscience 2013 Abstracts 599.01. Society for Neuroscience, San Diego, CA.
Summary: Cholinergic transmission plays a predominant role in memory processes, and loss of basal forebrain cholinergic innervation of the hippocampus has been correlated with memory impairment in Alzheimer’s disease (AD), as well as in decreased hippocampal neurogenesis in rats. Using a rat model of AD-like basal forebrain cholinergic cell loss, our lab has previously shown that central administration of a muscarinic receptor agonist, oxotremorine, for 4 weeks could reverse the spatial working memory deficit triggered by cholinergic denervation and induce hippocampal neurogenesis. The goal of the present study was to examine whether effects of chronic oxotremorine treatment persist beyond the treatment period, possibly indicating a disease-altering effect of the drug, particularly on memory function. Adult female Sprague Dawley rats were injected intracerebroventricularly (icv) with the immunotoxin 192-IgG-saporin (SAP), to induce AD-like basal forebrain cholinergic cell loss. After a 5 week recovery period, the rats then received 8 weeks of icv infusion of either oxotremorine or saline via osmotic minipump. Behavioral testing in a partially baited radial arm maze began 4 weeks after oxotremorine treatment was discontinued. To analyze cell proliferation, rats received intraperitoneal injections of BrdU either during the first 2 weeks of treatment, or at the end of behavioral testing. One month after oxotremorine treatment was discontinued, SAP-lesioned rats showed persistent improvements in radial arm maze acquisition, such that there was no difference in performance among sham/saline, sham/oxotremorine, and SAP/oxotremorine groups. SAP-lesioned rats treated with saline, however, still showed significant impairments compared to the other groups. Neuropathological and stereological analyses of these brains are ongoing, including analysis of hippocampal neurogenesis and neuronal cell counts in both basal forebrain and hippocampal regions. In a parallel cohort of rats analyzed at the end of the 8 week treatment period, initial results indicate no change in cholinergic cell density but a modest increase in the number of GABAergic cells in medial septum/diagonal band of lesioned rats treated with oxotremorine compared to saline. In the dentate gyrus (DG) of the hippocampus, increased numbers of cells labeled with BrdU during the first 2 weeks of treatment persisted to the end of the experiment, with an overall 1.5-fold increase in the number of BrdU labeled cells detected in the DG. These findings demonstrate that muscarinic stimulation is a promising target in the development of drugs to treat disorders involving cholinergic loss, such as AD.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Loss of medial prefrontal cortical cholinergic projections increases preference for an immediately available reward in a delay discounting task.
Burk JA, Yonezaki K (2013) Loss of medial prefrontal cortical cholinergic projections increases preference for an immediately available reward in a delay discounting task. Neuroscience 2013 Abstracts 288.02. Society for Neuroscience, San Diego, CA.
Summary: Attentional control is thought to regulate numerous processes, including impulsive choices. The cholinergic projections to the medial prefrontal cortex are thought to be part of a distributed neural circuit that maintains attentional control. In the present experiment, male FBNF1 hybrid rats were trained in a delay discounting task that involved a choice between a small, immediately available reward and a larger reward. The larger reward was also immediately available at the beginning of the test session and then the delay to receive this reward was progressively increased within a session (0-40 s). After reaching stable performance levels, rats then either received infusions of the cholinergic immunotoxin, 192IgG-saporin, or vehicle into the medial prefrontal cortex. After recovering from surgery, rats were tested in the same delay discounting task that had been trained prior to surgery. Relative to sham-lesioned animals, rats with a loss of the cholinergic projections to the medial prefrontal cortex exhibited an increased preference for selecting the smaller, immediate reward. Subsequent administration of nicotine (0.0, 0.1, 0.2, 0.4 mg/kg, ip) did not substantially alter the effects of the lesion on delay discounting performance. The present results suggest that medial prefrontal cortical cholinergic projections contribute to choice behavior based upon delay to reward access and reward magnitude. Moreover, these results are consistent with the idea that disruption of attentional control can increase impulsive choices.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Selective basal forebrain cholinergic deficits reduce glucose metabolism, cholinergic and GABAergic system in the cingulate cortex.
Lee J, Jeong D, Oh J, Lee J, Chang W, Cho Z, Chang J (2013) Selective basal forebrain cholinergic deficits reduce glucose metabolism, cholinergic and GABAergic system in the cingulate cortex. Neuroscience 2013 Abstracts 45.12. Society for Neuroscience, San Diego, CA.
Summary: Reduction of brain glucose metabolism and degeneration of cholinergic basal forebrain neurons are common features in Alzheimer’s disease and have been correlated with memory function. Although regions representing glucose hypometabolism in Alzheimer’s disease patients are target sites of cholinergic basal forebrain neurons, an interaction between cholinergic denervation and glucose hypometabolism is still unclear. To evaluate the changes in glucose metabolism in regions relevant to basal forebrain cholinergic deficits, we damaged basal forebrain cholinergic neurons of rats using 192 IgG-saporin. After 3 weeks, lesioned animals were tested by water maze test or analyzed using 18F-2-fluoro-2-deoxyglucose positron emission tomography. During the probe test in the water maze, performance of the lesion group decreased, considering time spent in both the target quadrant and platform zone. Glucose metabolism in the cingulate cortex of the lesion group decreased compared with the normal group. Additionally, acetylcholinesterase activity and glutamate decarboxylase 65/67 expression both declined in the cingulate cortex. Our results reveal that spatial memory impairment of animals in which basal forebrain cholinergic neurons are selectively damaged is associated with a decline in functions of GABAergic, cholinergic, and glutamatergic systems associated with glucose hypometabolism in the cingulate cortex.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Neuroprotective effects of donepezil against cholinergic depletion.
Cutuli D, De Bartolo P, Caporali P, Tartaglione AM, Oddi D, D’Amato FR, Nobili A, D’Amelio M, Petrosini L (2013) Neuroprotective effects of donepezil against cholinergic depletion. Alzheimers Res Ther 5(5):50. doi: 10.1186/alzrt215
Summary: Acetylcholinesterase inhibitors appear to be one of the only pharmacological tools available to reduce cognitive deficits caused by the loss of cholinergic neurons in the basal forebrain. Here the authors pre-treated rats with the aceytlcholinesterase inhibitor donepezil before administering 0.5 μg of 192-IgG-SAP (Cat. #IT-01) into each side of the medial septum. Analysis of working memory, spatial discrimination, social novelty preference, and ultrasonic localizations, along with measuring hippocampal and neocortical caspase-3 activity indicates that donepezil pre-treatment ameliorates some effects of the cholinergic depletion.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Modeling fall propensity in Parkinson’s disease: deficits in the attentional control of complex movements in rats with cortical-cholinergic and striatal-dopaminergic deafferentation.
Kucinski A, Paolone G, Bradshaw M, Albin RL, Sarter M (2013) Modeling fall propensity in Parkinson’s disease: deficits in the attentional control of complex movements in rats with cortical-cholinergic and striatal-dopaminergic deafferentation. J Neurosci 33(42):16522-16539. doi: 10.1523/JNEUROSCI.2545-13.2013
Summary: Parkinson’s disease produces a range of symptoms, some of which are unresponsive to therapies such as levodopa. These nonmotor symptoms include cognitive impairments and deficiencies in gait and balance. Here the authors develop a system to assess fall propensity in rats and examine the interaction between loss of cortical cholinergic and striatal dopaminergic afferents. Rats received 160-ng injections of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis and substantia innominata of the basal forebrain. The results indicate that the dual lesions result in diminished striatal control of complex movement.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Concordance between in vivo and postmortem measurements of cholinergic denervation in rats using PET with [18F]FEOBV and choline acetyltransferase immunochemistry.
Parent MJ, Cyr M, Aliaga A, Kostikov A, Schirrmacher E, Soucy JP, Mechawar N, Rosa-Neto P, Bedard MA (2013) Concordance between in vivo and postmortem measurements of cholinergic denervation in rats using PET with [18F]FEOBV and choline acetyltransferase immunochemistry. EJNMMI Res 3(1):70. doi: 10.1186/2191-219X-3-70
Summary: Positron emission tomography (PET) imaging agents have been developed for the quantitative evaluation of cholinergic systems in vivo, and in this work the authors examine the concordance between the in vivo use of PET and post-mortem analysis of cholinergic damage. Rats received unilateral 0.2-0.25 μg injections of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis. Animals were scanned using [18F]fluoroethoxybenzovesamicol, then sacrificed for cholineacetyltransferase immunohistochemistry. The results support the use of PET as an in vivo method for analyzing the loss of cholinergic neurons.
Related Products: 192-IgG-SAP (Cat. #IT-01)