alzheimers-disease

Dobryakova Y, Bolshakov A, Zaichenko M, Stepanichev M, Markevich V (2018) Behavioral effects of immunotoxin 192IgG-saporin depends on the type of its administration to rats. FENS 2018 Abstracts F055. Federation of European Neuroscience Societies, Berlin, Germany.

Summary: It is known that degeneration of cholinergic neurons is one of key events during development of Alzheimer’s disease. We used immunotoxin 192IgG-saporin, a conjugate of antibody to p75/NFGR receptor with saporin, to induce the cholinergic deficit in the hippocampus. Here, we compared effects of intracerebroventricular (i.c.v.) and intraseptal injection of 192IgG-saporin on the learning performance in rats. Immunohistochemical analysis of the ChAT stained sections showed that both types of 192IgG-saporin injection led to a strong loss ChAT-positive neurons in septal area compared to control. Behavioral testing began 3 weeks after the injection. We found that, in Morris Water Maze, i.c.v. injected rats had longer latencies to reach the platform and higher distance swam compared to control when the animals learned to find platform. We found that during probe trial, when the platform was removed from the maze, i.c.v.-treated rats spent significantly less time in a quadrant, where the platform was during training, and swam shorter distance in it, as compared to the control animals. Rats treated intraseptally with the immunotoxin had no behavioral deficits in the Morris Water Maze. In the beam walking test both groups of rats showed small but significant reduction of motor performance (p<0.05). In contrast, locomotor and exploratory activity in the open field task was affected only by intraseptal toxin administration as compared to the control. In conclusion, our data suggest that different types of immunotoxin administration leads to different disturbances in behavior. The work was supported by Grant of Russian Science Foundation No 16-15-10403.

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

Shin J, Kong C, Lee J, Na YC, Chang WS, Chang JW (2018) Improvements in cognitive function after focused ultrasound are associated with changes in hippocampal cholinergic activity and neurogenesis. FENS 2018 Abstracts C038. Federation of European Neuroscience Societies, Berlin, Germany.

Summary: Introduction: Alzheimer’s disease is irreversible and progressive neurodegenerative disorder that destroys memory and cognitive function. Recently, focused ultrasound (FUS) has been demonstrated that FUS- mediated BBB opening induces an increase in hippocampal neurogenesis in adult rodents. In this study, we investigated the effects of FUS on memory and cognitive function after 192 IgG-saporin lesioning. Materials and Methods: The present study utilized adult male Sprague-Dawley rats (200-250 g). Animals were divided into the three groups: Sham group (PBS injection), Lesion group (saporin injection), FUS group (saporin + FUS treatment). Lesion groups were injected bilaterally into the lateral ventricle. Rats were sonicated by using a single-element transducer with microbubble. The acoustic parameters for each sonication are: pressure amplitude 0.3 MPa, pulse length 10 ms, burst repetition frequency 1 Hz, and a duration of 120 s. BrdU was intraperitoneally injected 2 times per day for 4 consecutive days starting 24 hours after sonication. Two weeks after IgG-saporin administration, spatial memory was tested with the Morris water maze training. Results: In the water maze test, the FUS groups were significantly increased in number of crossing and platform zone, compared to the lesion group. We confirmed that the number of BrdU+, DCX+, and NeuN+ were significantly increased in the dentate gyrus following FUS sonication, compared to the lesion groups. Conclusion: Our results suggest that FUS treatments led to spatial memory improvement in cholinergic deficits rat model. These provided evidences indicate that reason of the behavior change may be induced by increase of acetylcholine activity and neuronal plasticity.

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

Pintus R, Riggi M, Cannarozzo C, Valeri A, de Leo G, Romano M, Gulino R, Leanza G (2018) Essential role of hippocampal noradrenaline in the regulation of spatial working memory and TDP‐43 tissue pathology. J Comp Neurol 526:1131-1147. doi: 10.1002/cne.24397

Objective: To determine the noradrenergic contribution to cognitive and histopathological changes in Alzheimer’s Disease.

Summary: Integrity of ascending noradrenergic inputs to the hippocampus may be required for the regulation of specific aspects of learning and memory and to prevent TDP-43 tissue pathology.

Usage: Anti-DBH-SAP was used at a dose of 0.50 µg dissolved in sterile PBS.

Related Products: Anti-DBH-SAP (Cat. #IT-03)

Zhuravin IA, Dubrovskaya NM, Tumanova NL, Vasilev DS, Nalivaeva NN (2018) Ontogenetic and phylogenetic approaches for studying the mechanisms of cognitive dysfunctions. Evolutionary Physiology and Biochemistry – Advances and Perspectives: InTech 714-741. doi: 10.5772/intechopen.73666

Summary: The effectiveness of the studies of the pathogenesis of AD and search for the strategies of its prevention and treatment depend on appropriate modeling of the pathological conditions in the brain leading to AD. Traditionally, the main focus on designing animal models of AD was related to the identification of brain areas and mediator systems related to memory. One model employed injections of a monoclonal antibody against growth factor receptor conjugated with saporin (192 IgG-saporin), which also resulted in the loss of cholinergic neurons and cognitive disorder

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

Kong C, Shin J, Lee J, Koh C-S, Yoon M-S, Na Y, Chang J, Chang W (2017) Improvements in memory after focused ultrasound are associated with changes in hippocampal cholinergic activity and neurogenesis. Neuroscience 2017 Abstracts 201.12 / C29. Society for Neuroscience, Washington, DC.

Summary: Abstract Introduction: Alzheimer’s disease is characterized pathologically by neurofibrillary tangles, amyloid plaques, gliosis, synaptic loss and cholinergic deficits. Recently, cell proliferation and neurogenesis was reported to have increased when the blood brain barrier (BBB) was disrupted by Focused ultrasound (FUS) with microbubbles. Previously, we have demonstrated that the cholinergic cell decreases in 192 IgG-saporin rat model, and that decrease in cholinergic cell is associated to decrease in cognitive behavior. The purpose of this study was to determine if the learning and memory abilities of the 192 IgG-saporin rat model are improved by FUS. Materials and Methods: Animals were divided into the four groups: Sham group (PBS injection), Lesion group (saporin injection), FUS-3 and FUS-10 groups (After 3 and 10 days after saporin injection, FUS treatment). Sprague-Dawley rats (200-250g) were injected bilaterally with 192 IgG-saporin into the ventricle. Rats were sonicated using a single-element transducer (frequency 0.5 MHz) with microbubble. The acoustic parameters used for each sonication are: pressure amplitude 0.3 MPa, pulse length 10 ms, burst repetition frequency 1 Hz, and a duration of 120 s. To confirm cell proliferation, BrdU was intraperitoneally injected 2 times per day for 4 consecutive days starting 24 hours after FUS sonication. Two weeks after IgG-saporin administration, spatial memory was tested with the Morris water maze training for 5 days and the final test was performed. Results: In the water maze test, the FUS groups had a higher number of crossing times and staying time in the platform zone than the lesion group. Also, the FUS-3 group was higher than for the FUS-10 group. We confirmed that the amounts of DCX , NeuN , and BrdU were different between the FUS group and the lesion group. Conclusion: Our results suggest that FUS sonication facilitates recovery of memory and learning abilities in cholinergic deficits rat model. Moreover, the results suggest that neurogenesis is correlated with the mechanism of cognitive behavior recovery.

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

Lee S, Cho W, Lee Y, Han J (2018) Impact of chronic stress on the spatial learning and GR-PKAc-NF-κB signaling in the hippocampus and cortex in rats following cholinergic depletion. Mol Neurobiol 55:3976-3989. doi: 10.1007/s12035-017-0620-5

Objective: Examine the effects of chronic stress on cognitive status and GR-PKAc-NF-κB signaling in rats with a loss of cholinergic input to the hippocampus and cortex.

Summary: The activation of NF-κB induced by cholinergic depletion appears to be aggravated by chronic stress, and this might explain the increased susceptibility of patients with Alzheimer’s disease to stress since activation of NF-κB is associated with stress.

Usage: Male Sprague-Dawley rats received injections of 192 IgG-SAP dissolved in sterile 0.01 M PBS) at a concentration of 0.25 μg/μl.

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

Martínez-Gardeazabal J, González de San Román E, Moreno-Rodríguez M, Llorente-Ovejero A, Manuel I, Rodríguez-Puertas R (2017) Lipid mapping of the rat brain for models of disease. Biochim Biophys Acta Biomembr 1859:1548-1557.. doi: 10.1016/j.bbamem.2017.02.011

Objective: To map the spatial distribution of different lipid species in the rat central nervous system (CNS) using IMS to find a possible relationship between anatomical localization and physiology. The data obtained were subsequently applied to a model of neurological disease, the 192IgG-saporin lesion model of memory impairment.

Summary: The specific distribution of different lipids supports their involvement not only in structural and metabolic functions but also as intracellular effectors or specific receptor ligands and/or precursors. Moreover, the specific localization in the CNS described here will enable us to analyze lipid distribution to identify their physiological conditions in rat models of neurodegenerative pathologies, such as Alzheimer’s disease.

Usage: 192 IgG-SAP in aCSF (135 ng/1 μl/hemisphere; 0.25 μl/min) was administered.

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

Gelfo F, Cutuli D, Nobili A, De Bartolo P, D’Amelio M, Petrosini L, Caltagirone C (2017) Chronic lithium treatment in a rat model of basal forebrain cholinergic depletion: Effects on memory impairment and neurodegeneration. J Alzheimers Dis 56:1505-1518. doi: 10.3233/JAD-160892 PMID: 28222508

Objective: To evaluate the potential beneficial effects of a chronic lithium treatment in preventing the damage that a basal forebrain cholinergic neurodegeneration provokes.

Summary: The chronic lithium treatment significantly rescued memory performances but did not modulate ChAT availability and caspase-3 activity. The present findings support the lithium protective effects against the cognitive impairment that characterizes the brain cholinergic depletion.

Usage: Neurodegeneration was induced by injecting the immunotoxin 192 IgG-SAP in the medial septum (0.5 ug/side) and nucleus basalis magnocellularis (0.4 ug/side).

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

Joly S, Lamoureux S, Pernet V (2017) Nonamyloidogenic processing of amyloid beta precursor protein is associated with retinal function improvement in aging male APP. Neurobiol Aging 53:181-191. doi: 10.1016/j.neurobiolaging.2017.02.004 PMID: 28262325

Objective: To determine amyloid beta role in the aging retina in Alzheimer’s Disease

Summary: Retinal-specific processing of amyloid may confer protection against AD and selectively preserve cone-dependent vision during aging.

Usage: Immunohistochemistry 1:1000

Related Products: Melanopsin Rabbit Polyclonal (Cat. #AB-N38)

Kelly SC, Nelson PT, Counts SE (2017) Featured Article: The locus coeruleus: a potential link between cerebrovascular and neuronal pathology in Alzheimer’s disease. Targeting Trends 18

Related Products: Anti-DBH-SAP (Cat. #IT-03), Mouse IgG-SAP (Cat. #IT-18)

Read the featured article in Targeting Trends.

See Also:

• Kelly SC et al. The locus coeruleus: a potential link between cerebrovascular and neuronal pathology in Alzheimer’s disease. Neuroscience 2016 Abstracts 786.11 / H7, 2016. Society for Neuroscience, San Diego, CA