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Cholinergic modulation targeting medial prefrontal cortex leads to behavior deficit in interval timing task
Zhang Q, De Corte B, Jung D, Kim Y, Geerling J, Narayanan N (2018) Cholinergic modulation targeting medial prefrontal cortex leads to behavior deficit in interval timing task. Neurology 90 (15 Supplement):P5.195.
Objective: To determine the effect of cholinergic lesion targeting medial prefrontal cortex on interval timing behavior.
Summary: Mice receiving medial prefrontal mu-p75-saporin injection performed poorly compared to control mice in interval timing task. Cholinergic lesion targeting medial prefrontal cortex caused interval timing behavior deficit in wild type mice.
Usage: mu-p75-SAP, a toxin targeting cholinergic neurons, into the bilateral medial prefrontal cortical regions of wild type mice pre-trained in interval timing task. Control mice (also pre-trained in interval timing task, n=8) received stereotactic injection of Rabbit IgG-SAP.
Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)
Real‐time electrochemical monitoring of choline during systemic inflammation in the freely‐ moving mouse
Doyle S, Baker KL, Cunningham C, Lowry JP (2018) Real‐time electrochemical monitoring of choline during systemic inflammation in the freely‐ moving mouse. Monitoring Molecules in Neuroscience . 17th International Conference, Oxford, UK
Summary: The loss of cholinergic innervation (mu p75‐SAP lesion in the basal forebrain) abolished the scopolamine‐induced choline increase in the hippocampus.
Related Products: mu p75-SAP (Cat. #IT-16)
Acute down-regulation of BDNF signaling does not replicate exacerbated amyloid-β levels and cognitive impairment induced by cholinergic basal forebrain lesion
Turnbull MT, Boskovic Z, Coulson EJ (2018) Acute down-regulation of BDNF signaling does not replicate exacerbated amyloid-β levels and cognitive impairment induced by cholinergic basal forebrain lesion. Front Mol Neurosci 11:51. doi: 10.3389/fnmol.2018.00051
Objective: To determine if degeneration of BFCNs causes a decrease in neurotrophin levels in innervated brain areas, which in turn promotes the development of Amyloid beta pathology and cognitive impairment.
Summary: Lesion of septo-hippocampal BFCNs in a pre-symptomatic transgenic amyloid AD mouse model (APP/PS1 mice) increases soluble Ab levels in the hippocampus, and induces cognitive deficits in a spatial memory task that are not seen in either unlesioned APP/PS1 or non-transgenic littermate control mice. Cognitive decline and Amyloid-beta pathology induced by cholinergic basal forebrain neuron loss occur independent of dysfunctional neuronal BDNF signaling, and may therefore be directly underpinned by reduced cholinergic neurotransmission.
Usage: To lesion BFCNs, a single infusion of murine p75-SAP or control rabbit IgG-SAP (0.4 mg/ml) was stereotaxically injected into the basal forebrain.
Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)
Cholinergic basal forebrain lesion decreases neurotrophin signaling without affecting tau hyperphosphorylation in genetically susceptible mice.
Turnbull M, Coulson E (2017) Cholinergic basal forebrain lesion decreases neurotrophin signaling without affecting tau hyperphosphorylation in genetically susceptible mice. J Alzheimers Dis 55:1141-1154.. doi: 10.3233/JAD-160805
Summary: Alzheimer’s disease(AD) is a progressive, irreversible neurodegenerative disease that destroys memory and cognitive function. Aggregates of hyperphosphorylated tau protein are a prominent feature in the brain of patients with AD, and area major contributor to neuronal toxicity and disease progression. However, the factors that initiate the toxic cascade that results in tau hyperphosphorylation in AD are unknown. The authors investigated whether degeneration of basal forebrain cholinergic neurons (BFCNs) and/or resultant decrease in neurotrophin signaling cause aberrant tau hyperphosphorylation. Two-month-old male and female pR5 mice were infused with murine p75-SAP (Cat. #IT-16) at a concentration of 0.4 mg/ml or 0.4 mg/ml of control Rabbit IgG-SAP (Cat. #IT-35) using a 30G needle attached to a 5 ml Hamilton syringe and pump. The needle was lowered into the medial septum according to coordinates in a mouse brain atlas, and the toxin was infused at a rate of 0.4 ul/min (1.5 u total volume). The results reveal that the loss of BFCNs in pre-symptomatic pR5 tau transgenic mice results in a decrease in hippocampal brain-derived neurotrophic factor levels and reduced TrkB receptor activation. However, there was no exacerbation of the levels of phosphorylated tau or its aggregation in the hippocampus of susceptible mice. Furthermore the animals’ performance in a hippocampal-dependent learning and memory task was unaltered, and no changes in hippocampal synaptic markers were observed. This suggests that tau pathology is likely to be regulated independently of BFCN degeneration and the corresponding decrease in hippocampal neurotrophin levels, although these features may still contribute to disease etiology.
Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)
Effects of brain-derived neurotrophic factor-pretreated neuron stem cell transplantation on Alzheimer’s disease model mice
Li T, Yu Y, Cai H (2015) Effects of brain-derived neurotrophic factor-pretreated neuron stem cell transplantation on Alzheimer’s disease model mice. Int J Clin Exp Med 8:21947-21955.
Summary: In order to generate the AD mouse model, mu p75-SAP (1-1.2 μg/μL) was injected to the bilateral icv areas.
Related Products: mu p75-SAP (Cat. #IT-16)
Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations.
Kim T, Thankachan S, McKenna J, McNally J, Yang C, Choi J, Chen L, Kocsis B, Deisseroth K, Strecker R, Basheer R, Brown R, McCarley R (2015) Cortically projecting basal forebrain parvalbumin neurons regulate cortical gamma band oscillations. Proc Natl Acad Sci U S A 112:3535-3540. doi: 10.1073/pnas.1413625112
Summary: Measurements of cortical EEG capture gamma band oscillations (GBO). Abnormalities in these GBO have been found in some neuropsychiatric disorders such as Alzheimer’s disease and schizophrenia. The authors analyzed GBO neuronal groups by administering 650-ng bilateral icv injections of mu p75-SAP (Cat. #IT-16) to mice to determine the role of basal forebrain cholinergic neurons in the generation of GBO. The results indicate GABAergic basal forebrain neurons containing parvalbumin were important for GBO integrity, but cholinergic neurons in the basal forebrain were not involved.
Related Products: mu p75-SAP (Cat. #IT-16)
Activation of the mouse primary visual cortex by medial prefrontal subregion stimulation is not mediated by cholinergic basalo-cortical projections.
Nguyen H, Huppé-Gourgues F, Vaucher E (2015) Activation of the mouse primary visual cortex by medial prefrontal subregion stimulation is not mediated by cholinergic basalo-cortical projections. Front Syst Neurosci 9:1. doi: 10.3389/fnsys.2015.00001
Summary: Mice received 1 μg icv injections of mu p75-SAP (Cat. #IT-16) to eliminate NGFr-positive cells. The results indicate a link between the prelimbic and infralimbic cortices and the primary visual cortex.
Related Products: mu p75-SAP (Cat. #IT-16)
The effects of targeted intracerebral saporin injection on recovery from stroke
Becker A, Goldberg M (2014) The effects of targeted intracerebral saporin injection on recovery from stroke. Neuroscience 2014 Abstracts 800.09. Society for Neuroscience, Washington, DC.
Summary: It is well known that the diffuse neuromodulatory systems of the brain play a role in cortical plasticity that may extend to cortical reorganization after brain injury. The basal forebrain cholinergic system in particular is necessary for both cortical plasticity and behavioral recovery from cortical electrolytic lesions. The role of the cholinergic system in recovery from stroke has never been directly investigated. In this experiment, we asked the question: is the basal forebrain cholinergic system in the mouse necessary for behavioral recovery from stroke? To answer this question, we administered intracerebral injections of the selective immunotoxin mu p75-saporin bilaterally to the cholinergic nucleus basalis in young adult mice. Using choline acetyltransferase immunohisochemistry, cresyl violet staining, and fluoro-jade B staining we discovered a dose at which these injections eliminate local cholinergic neurons while leaving other cell types and cholinergic cells outside the nucleus basalis unharmed. We report the effects of these injections on behavioral recovery from a subsequently induced photothrombotic cortical ischemic stroke.
Related Products: mu p75-SAP (Cat. #IT-16)
Immunolesion-induced loss of cholinergic projection neurones promotes beta-amyloidosis and tau hyperphosphorylation in the hippocampus of triple-transgenic mice.
Hartig W, Saul A, Kacza J, Grosche J, Goldhammer S, Michalski D, Wirths O (2014) Immunolesion-induced loss of cholinergic projection neurones promotes beta-amyloidosis and tau hyperphosphorylation in the hippocampus of triple-transgenic mice. Neuropathol Appl Neurobiol 40(2):106-120. doi: 10.1111/nan.12050
Summary: 3xTg transgenic mice were treated with 2 μg of mu p75-SAP (Cat. #IT-16) into the right lateral ventricle to eliminate cholinergic neurons in the basal forebrain. These mice already have age-dependent β-amyloidosis and tau hyperphosphorylation. This new model supplies a potential framework in which to study the entire pathology of Alzheimer’s disease.
Related Products: mu p75-SAP (Cat. #IT-16)
Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration.
Laursen B, Mork A, Plath N, Kristiansen U, Frank Bastlund J (2014) Impaired hippocampal acetylcholine release parallels spatial memory deficits in Tg2576 mice subjected to basal forebrain cholinergic degeneration. Brain Res 1543:253-262. doi: 10.1016/j.brainres.2013.10.055
Summary: The Tg2576 mouse strain provides a limited model for Alzheimer’s disease because they do not display degeneration of cholinergic neurons in the basal forebrain – the other main hallmark of Alzheimer’s disease in humans. Using 0.9 μg icv injections of mu p75-SAP (Cat. #IT-16) the authors evaluated mice that had both Aβ deposition and cholinergic depletion. The data show that these mice display cognitive decline and compromised cholinergic levels, creating a viable model for Alzheimer’s disease.
Related Products: mu p75-SAP (Cat. #IT-16)