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The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease
Björklund A, Barker RA (2024) The basal forebrain cholinergic system as target for cell replacement therapy in Parkinson’s disease. Brain awae026. doi: 10.1093/brain/awae026 PMID: 38279949
Objective: Review the use of cholinergic cell replacement as a potential therapeutic strategy in Parkinson’s Disease (PD) and how rodent models of PD-like cognitive decline can be used by analyzing rodent and primate studies.
Summary: Although therapies targeting the cholinergic system have so far been focused mainly on patients with Alzheimer´s disease, PD with dementia may be a more relevant condition. In PD with dementia the Basal Forebrain system undergoes progressive degeneration, and the magnitude of cholinergic cell loss has been shown to correlate with the level of cognitive impairment. Thus, cell therapy aimed to replace the lost basal forebrain cholinergic neurons represents an interesting strategy to combat some of the major cognitive impairments in patients with PD dementia.
Usage: Rats were given 192-IgG-SAP (IT-01), 0.2-0.4 μg, delivered as a single 0.3-1.0 μl injection into either the substantia innominate/nucleus basalis of Meynert (SI/NBM) or the medial septum/ventral diagonal band (MS/VDB).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation
Wu D, Yu N, Gao Y, Xiong R, Liu L, Lei H, Jin S, Liu J, Liu Y, Xie J, Liu E, Zhou Q, Liu Y, Li S, Wei L, Lv J, Yu H, Zeng W, Zhou Q, Xu F, Luo MH, Zhang Y, Yang Y, Wang JZ (2023) Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation. Mol Neurodegener 18(1):23. doi: 10.1186/s13024-023-00614-7 PMID: 37060096
Objective: There is an urgent need to study the targeting strategy for the MS-hippocampus cholinergic pathway to rescue tau-impaired memory.
Summary: Abnormal tau accumulation and cholinergic degeneration are hallmark pathologies in the brains of patients with Alzheimer’s disease (AD). However, the sensitivity of cholinergic neurons to AD-like tau accumulation and strategies to ameliorate tau-disrupted spatial memory in terms of neural circuits still remain elusive. The authors found that cholinergic neurons with an asymmetric discharge characteristic in the MS-hippocampal CA1 pathway are vulnerable to tau accumulation. Photoactivating MS-CA1 cholinergic inputs within a critical 3 h time window during memory consolidation efficiently improved tau-induced spatial memory deficits in a theta rhythm dependent manner. 192-IgG-Saporin was used to create an Alzheimer’s Disease animal model.
Related Products: 192-IgG-SAP (Cat. #IT-01)
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Acute and chronic lipopolysaccharide-induced stress changes expression of proinflammatory cytokine genes in the rat brain region-specifically and affects learning and memory.
Zaichenko MI, Philenko P, Sidorina V, Grigoryan GA (2023) Acute and chronic lipopolysaccharide-induced stress changes expression of proinflammatory cytokine genes in the rat brain region-specifically and affects learning and memory. Biochemistry Moscow 88:526-538. doi: 10.1134/S0006297923040089
Objective: Goal of the work was to conduct comparative analysis of the effects of acute and chronic lipopolysaccharide- induced stress on the behavior of rats in the Morris water maze test and on expression of mRNA of proinflammatory cytokines and BDNF in different brain structures.
Summary: Chronic stress, depression, and other neuropsychiatric disorders have been often associated with inflammation processes and activity of the brain immune system. In order to investigate association of neuroinflammation with such disorders the model of proinflammatory bacterial lipopolysaccharide intoxication was used. In the experiments with rats, acute lipopolysaccharide (LPS)-induced stress improved learning in the Morris water maze and caused substantial increase of the TNF-α and IL-1β mRNA concentrations in the hippocampus and amygdala, but not in the frontal lobe in comparison with the control animals. Hprt and Ywhaz genes were selected for use as molecular biology reference genes based on the analysis of the rat hippocampus transcriptome from the work done by Dobryakova, Y.V. et. al (2018) Intracerebroventricular administration of 192IgG-saporin alters expression of microglia-associated genes in the dorsal but not ventral hippocampus.
Related Products: 192-IgG-SAP (Cat. #IT-01)
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Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease
Leanza G, Zorec R (2023) Towards astroglia-based noradrenergic hypothesis of Alzheimer’s disease. Function (Oxf) 4(1):zqac060., IT. doi: 10.1093/function/zqac060 PMID: 36590326
Summary: These results indicate a prominent role of NA-neurons vs. ACh neurons in impairments of working memory, relevant for AD, and are consistent with an astrocyte-specific metabolic impairment in a mouse model of intellectual disability.
Usage: Bilateral icv injection of 192-IgG-SAP and/or Anti-DBH-SAP
Related Products: 192-IgG-SAP (Cat. #IT-01), Anti-DBH-SAP (Cat. #IT-03)
Cannabinoid receptors and glial response following a basal forebrain cholinergic lesion
Llorente-Ovejero A, Bengoetxea de Tena I, Martínez-Gardeazabal J, Moreno-Rodríguez M, Lombardero L, Manuel I, Rodríguez-Puertas R (2022) Cannabinoid receptors and glial response following a basal forebrain cholinergic lesion. ACS Pharmacol Transl Sci 5(9):791-802. doi: 10.1021/acsptsci.2c00069 PMID: 36110372
Objective: The endocannabinoid system is involved in the control of learning, memory, and neuroinflammatory processes and plays a role in neurodegeneration, such as in Alzheimer’s disease (AD). The objective was to study the roles of cannabinoid receptors in the regulation of neuroinflammation.
Summary: Selective agonists and antagonists to the cannabinoid receptors CB1 and CB2 were studied for their binding to G-proteins after specific lesioning of the basal forebrain cholinergic neurons (BCFN) using 192-IgG-SAP. These neurons are the same cholinergic pathways that are lost in the early stages of Alzheimer’s disease (AD). In their study, an increase of microglia immunoreactivities (GFAP and Iba-1) and decrease of astrocyte immunoreactivities were seen which indicate microglia-mediated neuroinflammation. In cortical BFCN projection areas, CB1 receptor binding to Gi/o-proteins was upregulated and at the injection site, the area that showed the highest increase of microglia, only slight CB2 binding to Gi/o-proteins were detected. Dose: Rats received 135 ng/μLof 192IgG-saporin (1μL/hemisphere; 0.25μL/min).
Related Products: 192-IgG-SAP (Cat. #IT-01)
Long-term nucleus basalis cholinergic depletion induces attentional deficits and impacts cortical neurons and BDNF levels without affecting the NGF synthesis
Orciani C, Hall H, Pentz R, Foret MK, Do Carmo S, Cuello AC (2022) Long-term nucleus basalis cholinergic depletion induces attentional deficits and impacts cortical neurons and BDNF levels without affecting the NGF synthesis. J Neurochem doi: 10.1111/jnc.15683
Objective: To determine whether reciprocal interaction of basal forebrain cholinergic neurons (BFCN) impact neurotrophin availability and affect cortical neuronal markers.
Summary: There is a neuroprotective role of cholinergic neurotransmission in the adult, fully-differentiated cortex.
Usage: Immunolesioned BFCN projecting mainly to the cortex with 192-IgG-SAP (bilateral 0.5 ug/ul; 1.0 ul/hemisphere) in 2.5 month-old Wistar rats.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Differential role of GABAergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping.
Akmese C, Sevinc C, Halim S, Unal G (2022) Differential role of GABAergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping. bioRxiv 2022.07.21.500949. doi: 10.1101/2022.07.21.500949
Related Products: 192-IgG-SAP (Cat. #IT-01), GAT1-SAP (Cat. #IT-32)
Sensory and motor visual functions in Parkinson’s Disease with respect to freezing of gait symptoms
Alhassan M (2022) Sensory and motor visual functions in Parkinson’s Disease with respect to freezing of gait symptoms. J Ophthalmol & Vis Sci 7(2):1069.
Objective: This review article summarizes the results from previous studies focusing on visual functions in Parkinson’s Disease patients.
Summary: Freezing of gait (FOG) is considered to be a motor disorder symptom that affects some Parkinson Disease (PD) patients; however, it is hypothesized that sensory systems may also be involved in FOG. Visual functions include high contrast visual acuity, low contrast visual acuity, contrast sensitivity, Vernier acuity, mesopic vision, stereopsis, motion perception, and vergence eye movements and are all affected in PD patients with FOG patients having more deficits in some of these functions. FOG patients also had impairments in non-dopaminergic mediated functions which suggests greater impairment in two functions that involve cholinergic neurotransmitters. 192-IgG-SAP (Cat. IT-01) was used to create a PD rat animal model to study the contribution of the cholinergic system to motor functions. It was found that the fall rates were more frequent in rats, that were injected with dual 192 IgG-saporin /6-hydroxydopamine (6-OHDA) than rats with either isolated cholinergic or isolated dopaminergic lesions.
Related Products: 192-IgG-SAP (Cat. #IT-01)
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A novel anxiety process biomarker via electrovestibulography
Bosecke C (2022) A novel anxiety process biomarker via electrovestibulography. University of Manitoba Thesis.
Objective: Use electrophysiological technique of Electrovestibulography to measure field potentials caused by vestibular neurons in the ear canal in order to identify biomarkers associated with anxiety disorder.
Summary: Anxiety disorders have no known biomarkers and are diagnosed based on symptoms. Identifying biomarkers could help improve the accuracy of anxiety disorder diagnosis, but can be difficult because the brain regions implicated in anxiety are very deep within the brain.
Usage: 192 IgG-SAP (Cat. #IT-01) was used to lesion the cholinergic medial septum inputs to the hippocampus. 192 IgG-saporin was diluted to 0.35 µg/µl with sterile saline, and 0.4 µl was infused bilaterally into each ventral site of the medial septum.
Related Products: 192-IgG-SAP (Cat. #IT-01)
Chemical genetic activation of the cholinergic basal forebrain hippocampal circuit rescues memory loss in Alzheimer’s disease
Liu W, Li J, Yang M, Ke X, Dai Y, Lin H, Wang S, Chen L, Tao J (2022) Chemical genetic activation of the cholinergic basal forebrain hippocampal circuit rescues memory loss in Alzheimer’s disease. Alzheimers Res Ther 14(1):53. doi: 10.1186/s13195-022-00994-w
Related Products: 192-IgG-SAP (Cat. #IT-01)
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