alzheimers-disease

Nizari S, Carare RO, Romero IA, Hawkes CA (2019) 3D reconstruction of the neurovascular unit reveals differential loss of cholinergic innervation in the cortex and hippocampus of the adult mouse brain. Front Aging Neurosci 11:172. doi: 10.3389/fnagi.2019.00172

Objective: To further characterize the effect of the loss of cholinergic innervation on the NVU (neurovascular unit) in Alzheimer’s Disease.

Summary: Significantly less ChAT staining was detected in the medial septum of saporin-treated mice at 45 days post-surgery. This was accompanied by a significant decrease in cholinergic nerve fiber density in the hippocampus and the cortex. As expected, p75 NTR-negative neurons in the striatum were not affected by mu p75-SAP treatment.

Usage: In this study, the mu-p75-SAP was used to induce death of basal forebrain cholinergic neurons and their fiber projections. mu p75-SAP 0.5 µL (0.596 µg/µL) or 0.9% saline (n = 19) was injected into each ventricle.

Related Products: mu p75-SAP (Cat. #IT-16)

Moreno-Rodriguez M, Martinez-Gardeazabal J, Llorente-Ovejero A, Lombardero L, Manuel I, Rodriguez-Puertas R (2018) Learning and memory improvement mediated by CB1 cannabinoid receptors in animal models of cholinergic dysfunction. Neuroscience 2018 Abstracts 049.05 / S3. Society for Neuroscience, San Diego, CA.

Summary: The selective vulnerability of the basal forebrain cholinergic system (BFCS) is responsible for most of the clinical alterations in learning and memory processes that are characteristic of the Alzheimer’s disease (AD). The loss of cholinergic neurons and muscarinic receptors (MR) in the nucleus basalis of Meynert have been reported in AD. The endocannabinoid system is a neuromodulator of the BFCS, but there are controversial reports regarding the cannabinoid effects in learning and memory processes. The animal models of cholinergic impairment mimic the main histopathological and behavioral effects observed in patients. The MR antagonism, e.g. using scopolamine (SCOP), is used as a model of amnesia in rodents. The intraparenchymal administration of 192-IgG-saporin (SAP) in the nucleus basalis magnocellularis eliminates cholinergic neurons leading to learning and memory deficits. Then, the present study evaluates the modulation of spatial and working memory with the Barnes Maze following a subchronic treatment with a low dose (0.5 mg/kg) of WIN55,212-2 (WIN) in both the SCOP and SAP models of learning and memory deficit. In the SCOP model, the administration of WIN protects learning and memory impairment during the probe trial, recorded as the time spent in the target quadrant (WIN + SCOP: 78 ± 13 sec vs VEH + SCOP: 45 ± 3 sec; p < 0.001). A similar effect of the treatment was observed in the SAP model (SAP: 50 ± 3 sec vs SAP + WIN: 82 ± 7 sec; p < 0.001). This effect was specifically mediated by CB1 receptors, since it was blocked by the co-administration of the specific CB1 antagonist, SR141716A (0.5 mg/kg) (SAP: 49 ± 3 sec vs SAP + WIN + SR: 48 ± 5 sec). However, higher doses of WIN (3 mg/kg) induced negative effects in learning and memory in control (C) rats, but positive and comparable to the lower dose in the SAP model (C: 89 ± 3 sec, C + WIN-3 mg/kg: 48 ± 3 sec; SAP: 49 ± 3; SAP + WIN-3 mg/kg: 80 ± 12 sec; p < 0.001). The CB1 receptor activation by low doses of the cannabinoid agonist WIN are able to block the amnesic effects induced by SCOP and also the learning and memory impairment produced by the BFCS pathway degeneration. CB1 agonists could contribute to improve the clinical symptoms of AD. International application patent PCT/EP2018/054525.

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

Kong C, Shin J, Lee J, Koh C, Sim J, Na Y, Chang W, Chang J (2018) Improvements of cognitive function by focused ultrasound associated with adult hippocampal neurogenesis in immunotoxin 192-Saporin rat model of cholinergic degeneration. Neuroscience 2018 Abstracts 174.27 / JJJ31. Society for Neuroscience, San Diego, CA.

Summary: Introduction: Alzheimer’s disease is irreversible, 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 lesion. 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 using a single-element transducer 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. BrdU was intraperitoneally injected two 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. Also, we found that the expression level of BDNF and TrkB increased in FUS group. Conclusion: Our results suggest that FUS treatments led to spatial memory improvement in cholinergic deficits rat model. Therefore, this provides evidence that the behavior changes may be mediated by increased acetylcholine activity and neuronal plasticity. Furthermore, FUS may represent a promising treatment for neurodegenerative disease, including Alzheimer’s disease because neurogenesis is associated with memory and cognitive function.

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

Qian L, Milne MR, Shepheard S, Rogers ML, Medeiros R, Coulson EJ (2019) Removal of p75 neurotrophin receptor expression from cholinergic basal forebrain neurons reduces amyloid-β plaque deposition and cognitive impairment in aged APP/PS1 mice. Mol Neurobiol 56(7):4639-4652. doi: 10.1007/s12035-018-1404-2

Objective: To investigate the contribution of CBF neuronal p75NTR to the progression of Alzheimer’s Disease

Summary: Data indicate that a direct interaction between CBF-expressed p75NTR and Aβ does not contribute significantly to the regulation of Aβ load.

Usage: To lesion CBF neurons, a single infusion of mu 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)

Pitake S, Ralph PC, DeBrecht J, Mishra SK (2018) Atopic dermatitis linked cytokine interleukin-31 induced itch mediated via a neuropeptide natriuretic polypeptide b. Acta Derm Venereol 98:795-796. doi: 10.2340/00015555-2977

Objective: To determine if NPPB is involved as a neuropeptide in IL-31-mediated itch in atopic dermatitis (AD) via natriuretic polypeptide receptor A (NPRA) in the spinal cord.

Summary: This study reveals an important role of neuropeptide NPPB in AD that could provide a therapeutic target for alleviating chronic itch associated with AD.

Usage: To further demonstrate the IL-31-mediated itch response by NPRA receptors expressed in the spinal cord, Nppb-SAP (5 μg) was used to eliminate neurons expressing NPRA receptors in the spinal cord.

Related Products: Nppb-SAP (Cat. #IT-69)

Leanza G, Gulino R, Zorec R (2018) Noradrenergic hypothesis linking neurodegeneration-based cognitive decline and astroglia. Front Mol Neurosci 11:254. doi: 10.3389/fnmol.2018.00254

Objective: To examine noradrenergic dysfunction in AD-related cognitive decline in humans and its potential involvement in AD pathology and disease progression.

Summary: The authors discuss noradrenergic dysfunction in AD-related cognitive decline. The research focuses on animal models to allow the validation of the noradrenergic hypothesis of AD, including those based upon the Anti-DBH-SAP-mediated ablation of LC. The article also addresses how astrocytes may participate in the regulation of neurogenesis, a new strategy for preventing LC neuron loss.

Usage: DBH (–/–) knockout mice do not seem to offer the possibility to obtain partial or graded neurotransmitter depletions. In light of these limitations, the authors used Anti-DBH-SAP which is able to target noradrenergic neurons in the LC with unprecedented selectivity and efficiency. Anti-DBH-SAP was injected bilaterally into the LC.

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

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)