Moreno-Rodríguez M, Martínez-Gardeazabal J, Bengoetxea de Tena I, Llorente-Ovejero A, Lombardero L, González de San Román E, Giménez-Llort L, Manuel I, Rodríguez-Puertas R (2024) Cognitive improvement via cortical cannabinoid receptors and choline-containing lipids. Br J Pharmacol doi: 10.1111/bph.17381 PMID: 39489624

Objective: Authors hypothesized that activation of the endocannabinoid system may confer neuroprotection against cholinergic degeneration.

Summary: Degeneration, induced by 192-IgG-saporin, of baso-cortical cholinergic pathways resulted in memory deficits and decreased cortical levels of lysophosphatidylcholines (LPC). The cannabinoid agonist WIN55,212-2 restored cortical cholinergic transmission and LPC levels via activation of cannabinoid receptors. This activation altered cortical lipid homeostasis mainly by reducing sphingomyelins in lesioned animals. These modifications were crucial for memory recovery.

Usage: Basal forebrain cholinergic degeneration was induced following bilateral stereotaxic injection of 192IgG-saporin (130 ng/μl, IT-01) into the nucleus basalis magnocellularis (NBM).

Related Products: 192-IgG-SAP (Cat. #IT-01)

Shivakumar AB, Mehak SF, Jijimon F, Gangadharan G (2024) Extra-hippocampal contributions to social memory: The role of septal nuclei. Biol Psychiatry 6:835-847. doi: 10.1016/j.biopsych.2024.04.018 PMID: 38718881

Objective: Review neural circuit mechanisms that underlie social memory, with a special emphasis on the septum.

Summary: Understanding the complexities of the septohippocampal axis will allow targeted therapies to be developed to improve social memory deficits and enhance overall cognitive function.

Usage: Medial septum lesions in rats with 192-IgG-SAP (IT-01).

Related Products: 192-IgG-SAP (Cat. #IT-01)

See Also:

• Vale-Martinez A et al. Selective lesions of basal forebrain cholinergic neurons produce anterograde and retrograde deficits in a social transmission of food preference task in rats. Eur J Neurosci 16(6):983-998, 2002.
• Berger-Sweeney J, Stearns NA, Frick KM, Beard B, Baxter MG (2000) Cholinergic basal forebrain is critical for social transmission of food preferences. Hippocampus 10(6):729-738. doi: 10.1002/1098-1063(2000)10:6<729::AID-HIPO1010>3.0.CO;2-M PMID: 11153718

Kumbhare D, Rajagopal M, Toms J, Freelin A, Weistroffer G, McComb N, Karnam S, Azghadi A, Murnane KS, Baron MS, Holloway KL (2024) Deep brain stimulation of nucleus basalis of meynert improves learning in rat model of dementia. bioRxiv 2024.04.05.588271. doi: 10.1101/2024.04.05.588271 PMID: 38645266

Objective: To assess the effects of varying stimulation patterns and duration on learning in a dementia rat model.

Summary: Deep brain stimulation (DBS) of nucleus basalis of Meynert (NBM) has been considered a potential treatment for dementia, but more study is needed to determine the ideal parameters for NBM stimulation. 192-IgG-SAP (Cat. IT-01) was used to lesion cholinergic neurons of rats creating a rat model of dementia upon which NBM deep brain stimulation could be tested. The desired destruction of neurons was 70-80% cholinergic population lesioned, which through a panel of concentrations was determined to be a 0.50 μg dose. The rat models of dementia were then tested for ideal type and duration of deep brain stimulation to improve operant learning test performance.

Usage: 192-IgG-SAP was bilaterally injected in the NBM in the following amounts: 0.00 (control), 0.15, 0.30, 0.50, and 0.75 μg in 0.5 μl PBS.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Moreno-Rodríguez M, Martínez-Gardeazabal J, Bengoetxea de Tena I, Llorente-Ovejero A, Lombardero L, González de San Román E, Giménez-Llort L, Manuel I, Rodríguez-Puertas R (2024) Cortical lipids containing choline mediate cannabinoid-induced cognitive improvement. bioRxiv 2024.03.07.583670. doi: 10.1101/2024.03.07.583670

Objective: Investigate the neuroprotective effect of treatment with the CB1 cannabinoid agonist, WIN55,212-2, against cholinergic degeneration.

Summary: The endocannabinoid (eCB) system plays a role in modulating learning and memory processes controlled by cholinergic neurotransmission. The authors propose that activation of this system is neuroprotective against cholinergic degeneration, such as what occurs in Alzheimer’s disease (AD). In a 192-IgG-SAP (Cat. IT-01) induced model of AD, a restoration of memory and learning was observed when rats were administered the CB1 cannabinoid agonist, WIN55,212-2.

Usage: Rats received injections of 192-IgG-saporin (130 ng/µl) into the nucleus basalis magnocellularis.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Luna-Munguia H, Gasca-Martinez D, Garay-Cortes A, Coutiño D, Regalado M, de Los Rios E, Villaseñor P, Hidalgo-Flores F, Flores-Guapo K, Benito BY, Concha L (2024) Selective medial septum lesions in healthy rats induce longitudinal changes in microstructure of limbic regions, behavioral alterations, and increased susceptibility to status epilepticus. Mol Neurobiol 61(10):1-21. doi: 10.1007/s12035-024-04069-9 PMID: 38443731

Objective: To evaluate tissue changes after lesioning the medial septum (MS) of normal rats and assess how the depletion of specific neuronal populations alters the animals’ behavior and susceptibility to establishing a pilocarpine-induced status epilepticus.

Summary: Behaviorally, the GAT1-saporin injection impacted spatial memory formation, while 192-IgG-saporin triggered anxiety-like behaviors. Regarding the pilocarpine-induced status epilepticus, an increased mortality rate was observed. Selective septo-hippocampal modulation impacts the integrity of limbic regions crucial for certain behavioral skills and could represent a precursor for epilepsy development.

Usage: Injection of 192-IgG-SAP (375 ng/μl dissolved in sterile 0.1X PBS) and GAT1-SAP (325 ng/μl dissolved in sterile 0.1X PBS) into the MS to selectively target choline neuron or GABA populations of the medial septum, respectively.

Related Products: GAT1-SAP (Cat. #IT-32), 192-IgG-SAP (Cat. #IT-01)

Martínez-Gardeazabal J, Moreno-Rodríguez M, Llorente-Ovejero A, González de San Román E, Lombardero L, Bengoetxea de Tena I, Sustacha J, Matute C (2024) Cell lipotypes localization in brain by mass spectrometry imaging. bioRxiv doi: 10.1101/2024.02.02.578599

Objective: Characterizing the type of different central nervous system cells via mass spectrometry of their component lipids.

Summary: Different varieties of cells in the central nervous system perform different functions and, as a consequence, have different compositions. Using purified rat cell cultures of neurons, astrocytes, oligodendrocytes, microglia, and choroid plexus cells, a model was constructed to identify the localization of any brain cell through mass spectrum imaging of the lipid composition.

Usage: Injected 192-IgG-SAP (130 ng/µl) into the nucleus basalis magnocellularis (nbM) of rats.

Related Products: 192-IgG-SAP (Cat. #IT-01)

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)

Dobryakova YV, Gerasimov K, Spivak YS, Korotkova T, Koryagina A, Deryabina A, Markevich VA, Bolshakov AP (2023) The induction of long-term potentiation by medial septum activation under urethane anesthesia can alter gene expression in the hippocampus. Int J Mol Sci 24(16):12970. doi: 10.3390/ijms241612970 PMID: 37629149

Objective: To study changes in the expression of early genes in hippocampal cells in response to stimulation of the dorsal medial septal area (dMSA), leading to long-term potentiation in the hippocampus.

Summary: The data suggest that the induction of long-term potentiation by dMSA activation enhances the expression of select early genes in the hippocampus.

Usage: Injection into the medial septum area (MSA) at a rate of 0.2μL/min. The drug was infused at a concentration of 1.5μg/per rat.

Related Products: 192-IgG-SAP (Cat. #IT-01)

Akmese C, Sevinc C, Halim S, Unal G (2023) Differential role of GABaergic and cholinergic ventral pallidal neurons in behavioral despair, conditioned fear memory and active coping. Prog Neuropsychopharmacol Biol Psychiatry 125:110760. doi: 10.1016/j.pnpbp.2023.110760 PMID: 37031946

Objective: To investigate the role of the ventral pallidum (VP) in regulating the brain’s reward circuitry in appetitive behaviors and emotional regulation through GABAergic and Cholinergic lesions.

Summary: Using GAT1-SAP (GABAergic) or 192-IgG-SAP (cholinergic), injections were made into the VP to eliminate neurons in rats. These lesioned rats were subjected to fear conditioning tests, and it was shown that the VP may contribute to emotion regulation by suppressing active coping and promoting species-specific passive behaviors.

Usage: Bilateral injections of GAT1-SAP (325 ng/μl, 0.5 μl volume, 0.1 μl/min), 192-IgG-SAP (500 ng/μl in PBS, 0.5 μl volume, 0.1μl/min), or PBS (0.5 μl volume, 0.1 μl/min) into the Ventral Pallidum.

Related Products: GAT1-SAP (Cat. #IT-32), 192-IgG-SAP (Cat. #IT-01)

Zhou Y, Zhang K, Wang F, Chen J, Chen S, Wu M, Lai M, Zhang Y, Zhou W (2023) Polypyrimidine tract binding protein knockdown reverses depression-like behaviors and cognition impairment in mice with lesioned cholinergic neurons. Front Aging Neurosci 15:1174341. doi: 10.3389/fnagi.2023.1174341 PMID: 37181622

Objective: Examine the mechanisms of how knockdown of the RNA-binding protein polypyrimidine tract binding protein (PTB) reverses depression-like behavior and cognition impairment in mice with lesioned cholinergic neurons.

Summary: A specific loss of cholinergic neurons in the horizontal limb of the diagonal band of broca (HDB) is correlated with depression and dysfunction of cognition in mice. The authors induced cholinergic neuron loss via injection of 192-IgG-SAP. This was followed by injection of either antisense oligonucleotides or adeno-associated virus-shRNA in the injured area of HDB to knockdown PTB. Knockdown of PTB by these two approaches was found to relieve depression-like behaviors and alleviate cognitive impairment and the findings suggest that supplementing cholinergic neurons after PTB knockdown may be a therapeutic approach to reverse depression-like behaviors and cognitive impairment.

Usage: 192 IgG-saporin (Cat. IT-01) was injected bilaterally into the HDB at a volume of 0.25 μl with a concentration of 1 μg/μL, per side.

Related Products: 192-IgG-SAP (Cat. #IT-01)