alzheimers-disease

Scattoni ML, Adriani W, Calamandrei G, Laviola G, Ricceri L (2006) Long-term effects of neonatal basal forebrain cholinergic lesions on radial maze learning and impulsivity in rats. Behav Pharmacol 17(5-6):517-524. doi: 10.1097/00008877-200609000-00018

Summary: Work in the last decade has focused on clarifying the role of cholinergic dysfunction in Alzheimer’s disease. 7 day-old rats received 0.21 µg of 192-Saporin (Cat. #IT-01) administered to the third ventricle, and were tested at 5 months of age in delay tolerance and a radial maze. Test results suggest that prolonged basal forebrain cholinergic hypofunction is detectable only when using highly complex tasks.

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

Traissard N, Herbeaux K, Cosquer B, Jeltsch H, Ferry B, Galani R, Pernon A, Majchrzak M, Cassel JC (2007) Combined damage to entorhinal cortex and cholinergic basal forebrain neurons, two early neurodegenerative features accompanying Alzheimer’s Disease: Effects on locomotor activity and memory functions in rats. Neuropsychopharmacology 32(4):851-871. doi: 10.1038/sj.npp.1301116

Summary: Two characteristics of Alzheimer’s disease (AD) are cholinergic dysfunction in the basal forebrain, and neuronal damage in the entorhinal cortex. Using 5 µg intracerebroventricular (icv) injections of 192-IgG-SAP (Cat. #IT-01), and 2.3 µg icv injections of OX7-SAP (Cat. #IT-02), locomotor activity, working, and reference memory of rats were examined. Although 192-IgG-SAP lesions caused limited deficits, rats receiving both lesions exhibited several behaviors associated with AD. The authors suggest that combining these lesions may be a more accurate model for AD than 192-IgG-SAP alone.

Related Products: 192-IgG-SAP (Cat. #IT-01), OX7-SAP (Cat. #IT-02)

Kolasa K, Parsons D, Harrell LE (2005) Time-dependent neurotrophins effect on cholinergic denervation and hippocampal sympathetic ingrowth following 192 IgG-saporin lesioning of medial septum. Neuroscience 2005 Abstracts 1004.4. Society for Neuroscience, Washington, DC.

Summary: In rat,injection of specific cholinotoxin,192 IgG-saporin into the medial septum results not only in a selective denervation of hippocampus(CD),but in an ingrowth of peripheral sympathetic fibers,originating from the superior cervical ganglion,into the hippocampus.This process has been termed hippocampal sympathetic ingrowth(HSI).A similar process,in which sympathetic noradrenergic axons invade hippocampus,may also occur in Alzheimer’s disease(AD). The severity of cognitive decline in AD patients has been linked to multiple factors including cholinergic and neurotrophic factors and their receptors,which undergo selective alterations throughout the progression of AD.It is known that the sites of synthesis of NGF(nerve growth factor),BDNF(brain derived-neurotrophic factor)and LIF (leukemia inhibitory factor)in rat septo-hippocampal system are predominantly hippocampal neurons.By using 192 IgG-saporin we have been able to mimic some of the cardinal features of AD e.x.cholinergic denervation and hippocampal sympathetic ingrowth and to study their effect on neurotrophins in dorsal hippocampus.Thus,2,8,and 12 weeks after injection of 192 IgG-saporin we measured NGF, BDNF and LIF protein and mRNA expression using Western blot and RT-PCR techniques, respectively.Choline acetyltransferase activity(ChAT) and norepinephrine(NE) concentration was also detected. Significant alterations were found in NGF and LIF protein expression(decrease at 8 weeks and increase at 12 weeks post lesions)in HSI group. Significant decrease of BDNF(mature form) protein expression was found in CD group over whole period of time. There was significant decrease found in BDNF mRNA expression in CD,with normalization in HSI group 12 weeks post lesions. Results of the study suggest that neurotrophins are affected by cholinergic denervation and may play an important role in regulation and development of HSI,which might be a beneficial phenomenon for restoration at least some of cognitive function.

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

Pedersen AF, Kostova V, Christensen E, Veng LM, Lohals R, Knudsen GM, Aznar S (2005) Intraventricular IgG192-saporin lesions lead to altered 5-HT2A receptor levels in the hippocampus. Neuroscience 2005 Abstracts 559.17. Society for Neuroscience, Washington, DC.

Summary: Background: Alzheimer’s disease (AD) is the most frequent neurodegenerative disorder in humans. One of the traits of the disease is the presence in the brain of beta-Amyloid plaques and loss of cholinergic neurons in the basal forebrain. Other transmittersystems especially serotonin may be involved in the patophysiology of AD. Clinical studies have observed a higher incidence of depression among AD patients and a higher risk of developing dementia when diagnosed with major depression. It is known that serotonin and serotonin receptors, among them 5-HT2A receptors (5-HT2AR), are involved in depression. Interestingly, recent PET-studies have shown lower 5-HT2AR levels in entorhinal cortex and hippocampus in early stages of AD. Objectives: Our aim was to investigate whether 5-HT2AR levels were affected in the hippocampus after lesioning the cholinergic neurons in the basal forebrain, thereby highlighting a possible interaction between the serotonergic and the cholinergic transmitter systems. Methods: Intraventricular injection of 5ug IgG192-Saporin or saline in adult Wistar male rats. After 20 weeks the rats were sacrificed and the hippocampus were isolated. After homogenisation the levels of 5-HT2AR were determined by western blot. Results: Downregulation of the 5-HT2AR levels were observed after 20 weeks. 5-HT2AR levels for animals receiving IgG192-Saporin for 1, 2 and 4 weeks will also be investigated. Conclusion: Our results show a direct effect of cholinergic lesions on hippocampal 5-HT2AR. This may be explained by a compensatory effect of the serotonergic system for the loss of cholinergic input as there may be a balance between these two systems in the hippocampus.

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

Yamazaki Y, Jia Y, Hamaue N, Sumikawa K (2005) Nicotine-induced switch in the nicotinic cholinergic mechanisms of facilitation of long-term potentiation induction. Eur J Neurosci 22(4):845-860. doi: 10.1111/j.1460-9568.2005.04259.x

Summary: The authors investigated cellular mechanisms underlying improved cognitive function in Alzheimer’s disease patients upon the administration of nicotine. To model Alzheimer’s disease in rats, 2 µg of 192-IgG-SAP (Cat. #IT-01) was injected into the lateral cerebral ventricle. Examination of the lesioned animals suggests that nicotine promotes the induction of long-term potentiation by enhancing N-methyl-D-aspartate responses, and suppressing acetylcholine-mediated mechanisms in pyramidal cells.

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

Guillemin GJ, Brew BJ, Noonan CE, Takikawa O, Cullen KM (2005) Indoleamine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer’s disease hippocampus. Neuropathol Appl Neurobiol 31(4):395-404. doi: 10.1111/j.1365-2990.2005.00655.x PMID: 16008823

Related Products: Quinolinic Acid Rabbit Polyclonal, Conjugated (Cat. #AB-T095)

Dudkin KN, Chueva V, Makarov FN, Bich TG, Roer AE (2005) Impairments in working memory and decision-taking processes in monkeys in a model of Alzheimer’s disease. Neurosci Behav Physiol 35(3):281-289. PMID: 15875490

Related Products: ME20.4-SAP (Cat. #IT-15), Anti-DBH-SAP (Cat. #IT-03)

Gil-Bea FJ, Garcia-Alloza M, Dominguez J, Marcos B, Ramirez MJ (2005) Evaluation of cholinergic markers in Alzheimer’s disease and in a model of cholinergic deficit. Neurosci Lett 375(1):37-41. doi: 10.1016/j.neulet.2004.10.062

Summary: Several markers of cholinergic function may be able to predict cognitive deficits due to disorders such as Alzheimer’s disease. The authors compared baseline measurements of acetylcholine, cholinacetyltransferase, and acetylcholinesterase (AChE) of rats against animals treated with 0.067 µg injections of 192-Saporin (Cat. #IT-01) into both hemispheres of the nucleus basalis magnocellularis. The results indicate that measurement of AChE activity is an inexpensive and reliable method to evaluate cholinergic function in rats as well as in humans.

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

Leung LS, Petropoulos S, Ma J, Shen B (2004) Cholinergic neurons in the basal forebrain participate in consciousness and general anesthesia. Neuroscience 2004 Abstracts 565.4. Society for Neuroscience, San Diego, CA.

Summary: Acetylcholine (Ach) in the brain has long been associated with consciousness. In this study, we assessed consciousness in rats by their EEG and behavioral responses to a general anesthetic. Cholinergic neurons in the nucleus basalis of Meynert (NbM) were lesioned by bilateral injection of toxin IgG192-saporin (0.15 μg at P1.4, L2.7, 7.7 mm below dura) in 10 adult male rats. Control (5 rats) had saline injected into the NbM. EEGs were recorded by electrodes placed in layer V of the frontal cortex (FC) and visual cortex (VC). Spectral analysis of the spontaneous EEGs in FC and VC during awake-immobility indicated that lesioned animals showed higher delta (0.8 to 4 Hz) and lower gamma (30- 58 Hz) power as compared to controls. Subsequent acetylcholinesterase staining (optical density) confirmed significant Ach depletion in both FC and VC, in the lesion as compared to the control group (P<0.002, Wilcoxon). When challenged with a normally subanesthetic dose of general anesthetic, the lesioned rats showed, as compared to controls, significantly longer durations of loss of righting and tail-pinch response after 5 mg/kg i.v. propofol (P<0.001), but not after 20 mg/kg i.p. pentobarbital or 2% halothane. In correspondence with the deep behavioral anesthesia, delta power at FC after propofol was significantly larger in lesioned than control rats. Lesioned rats, as compared to controls, also showed decreased locomotion (behavioral excitation) when given 2% halothane in a large chamber. In summary, a loss of Ach in the neocortex decreases the level of consciousness as indicated by increased delta and decreased gamma EEG, and by an increased sedative/ anesthetic response to propofol i.v. We suggest that patients with Alzheimer disease may show altered response to some general anesthetics.

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

Hawkes CA, Kar S (2004) Loss of basal forebrain cholinergic neurons by 192 igG-Saporin induces increased IGF-II/M6P receptor expression in select brain areas. Neuroscience 2004 Abstracts 92.1. Society for Neuroscience, San Diego, CA.

Summary: Alzheimer’s disease (AD) is characterized neuropathologically by the presence of extracellular amyloid plaques, intracellular neurofibrillary tangles and neuronal loss in selected brain areas, including basal forebrain cholinergic neurons, which project to the hippocampus and neocortex. Increasing evidence supports a role of the endosomal-lysosomal (EL) system in the pathophysiology of AD. A key component of the EL system is the insulin-like growth factor-II/mannose-6-phosphate (IGF-II/M6P) receptor, a single transmembrane domain glycoprotein which functions in the intracellular trafficking of lysosomal enzymes, and in the internalization of extracellular IGF-II and M6P-containing ligands. However, very little is known about the functional significance of this receptor in the brain. We examined expression of the IGF-II/M6P receptor and other markers of the EL system, at different time points following bilateral i.c.v. injection of 192 IgG-saporin. 192 IgG-saporin produced an almost complete loss of ChAT-positive neurons in the basal forebrain, as well as fibers in the hippocampus and frontal cortex, while striatal cholinergic neurons were unaffected. Western blotting and immunocytochemistry results indicate an upregulation of IGF-II/M6P receptor levels in the septum and frontal cortex. A modest increase was also observed in cathepsin D levels. The level of other EL markers, such as Rab5 and LAMP1, showed varied temporal and spatial changes. These results suggest that brain areas innervated by basal forebrain neurons, respond differently to the loss of cholinergic input and that elements of the EL system may be involved in cholinergic degeneration/compensatory responses of surviving neurons.

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