alzheimers-disease

Cutuli D, De Bartolo P, Caporali P, Tartaglione AM, Oddi D, D’Amato FR, Nobili A, D’Amelio M, Petrosini L (2013) Neuroprotective effects of donepezil against cholinergic depletion. Alzheimers Res Ther 5(5):50. doi: 10.1186/alzrt215

Summary: Acetylcholinesterase inhibitors appear to be one of the only pharmacological tools available to reduce cognitive deficits caused by the loss of cholinergic neurons in the basal forebrain. Here the authors pre-treated rats with the aceytlcholinesterase inhibitor donepezil before administering 0.5 μg of 192-IgG-SAP (Cat. #IT-01) into each side of the medial septum. Analysis of working memory, spatial discrimination, social novelty preference, and ultrasonic localizations, along with measuring hippocampal and neocortical caspase-3 activity indicates that donepezil pre-treatment ameliorates some effects of the cholinergic depletion.

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

Lee YS, Danandeh A, Baratta J, Lin CY, Yu J, Robertson RT (2013) Neurotrophic factors rescue basal forebrain cholinergic neurons and improve performance on a spatial learning test. Exp Neurol 249C:178-186. doi: 10.1016/j.expneurol.2013.08.012

Summary: It is thought that therapeutic treatments of the cholinergic system may be a viable treatment for Alzheimer’s disease. In order to examine this hypothesis the authors administered a total of 160 ng of 192-IgG-SAP (Cat. #IT-01) in the form of bilateral injections into the medial septum. The lesioned animals then received 4-week infusions of nerve growth factor, neurotrophin 3, or both into the lateral ventricles. Animals treated with any neurotrophin, either alone or as a combination, retained more ChAT-positive neurons and performed better on a delayed match-to-position task than control animals. The data strengthen the theory that exogenous neurotrophic factors ameliorate the effects of Alzheimer’s disease.

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

Gelfo F, Petrosini L, Graziano A, De Bartolo P, Burello L, Vitale E, Polverino A, Iuliano A, Sorrentino G, Mandolesi L (2013) Cortical metabolic deficits in a rat model of cholinergic basal forebrain degeneration. Neurochem Res 38(10):2114-2123. doi: 10.1007/s11064-013-1120-2

Summary: In this work the authors investigated the connection between cholinergic depletion caused by conditions such as Alzheimer’s disease and cerebral energy metabolism deficits. Rats received a 0.4-μg injection of 192-IgG-SAP (Cat. #IT-01) into the nucleus basalis magnocellularis. Neuronal metabolic activity was measured by assaying cytochrome oxidase (CO) activity. The unilateral injection produced a bilateral deficit in CO activity throughout the cortex, and the front and parietal cortices showed CO deficits before the lesion was complete. The data suggest a link between cholinergic hypofunctionality and metabolic deficit.

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

Ovsepian SV, Antyborzec I, O’Leary VB, Zaborszky L, Herms J, Oliver Dolly J (2013) Neurotrophin receptor p75 mediates the uptake of the amyloid beta (Abeta) peptide, guiding it to lysosomes for degradation in basal forebrain cholinergic neurons. Brain Struct Funct 219(5):1527-1541. doi: 10.1007/s00429-013-0583-x PMID: 23716278

Summary: Accumulation of β-amyloid in the brain is considered one of the main causes of Alzheimer’s disease. The increase in β-amyloid is accompanied by a reduction in levels of the high affinity nerve growth factor receptor (trkA) and cognitive impairment. The authors looked at levels of the low affinity nerve growth factor receptor (p75) that do not decline. Using a 0.8-μg injection of 192-Cy3 (Cat. #FL-01) into the medial prefrontal cortex of rats the authors assessed the transport of p75 and β-amyloid by microscopy. The results indicate that the primary destinations of both p75 and β-amyloid were the late endosome and lysosome.

Related Products: 192-IgG Mouse Monoclonal, Cy3-labeled (Cat. #AB-N43FL3)

Ramos-Rodriguez JJ, Pacheco-Herrero M, Thyssen D, Murillo-Carretero MI, Berrocoso E, Spires-Jones TL, Bacskai BJ, Garcia-Alloza M (2013) Rapid beta-amyloid deposition and cognitive impairment after cholinergic denervation in app/ps1 mice. J Neuropathol Exp Neurol 72(4):272-285. doi: 10.1097/NEN.0b013e318288a8dd

Summary: The authors investigated whether specific cholinergic neurodegeneration is responsible for the deposition of plaques. APPswe/PS1dE9 transgenic mice received bilateral icv injections of 1-1.2 μg of mu p75-SAP (Cat. #IT-16) into the basal forebrain. Although the transgenic mice show plaque deposition, they do not exhibit other signs of Alzheimer’s disease. Lesioned transgenic animals, however, displayed increased β-amyloid plaque deposition, increased Tau phosphorylation, and early memory impairment that worsened with age.

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

Matchynski JJ, Lowrance SA, Pappas C, Rossignol J, Puckett N, Sandstrom M, Dunbar GL (2013) Combinatorial treatment of tart cherry extract and essential fatty acids reduces cognitive impairments and inflammation in the mu-p75 saporin-induced mouse model of Alzheimer’s disease. J Med Food 16(4):288-295. doi: 10.1089/jmf.2012.0131 PMID: 23566055

Summary: The authors investigated the efficacy of a combinatorial therapy, Cerise Total-Body Rhythm (TBR) by treating mice with TBR prior to and following icv administration of 0.8 μg of mu p75-SAP (Cat. #IT-16).

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

Laursen B, Mork A, Plath N, Kristiansen U, Bastlund JF (2013) Cholinergic degeneration is associated with increased plaque deposition and cognitive impairment in APPswe/PS1dE9 mice. Behav Brain Res 240:146-152. doi: 10.1016/j.bbr.2012.11.012

Summary: Extracellular plaques containing amyloid β-peptides (Aβ) and cholinergic dysfunction are two of the main hallmarks of Alzheimer’s disease. Using a transgenic mouse line that displays an age-related increase in plaque deposition, the authors examined the relationship between cholinergic degeneration and Aβ overexpresssion. Mice received 0.9-μg bilateral icv injections of mu p75-SAP (Cat. #IT-16). Working memory was significantly impaired in lesioned mice with plaques, and the plaque burden was increased as compared to wild-type mice that also received a lesion.

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

Brayda-Bruno L, Mons N, Yee BK, Micheau J, Abrous DN, Nogues X, Marighetto A (2013) Partial loss in septo-hippocampal cholinergic neurons alters memory-dependent measures of brain connectivity without overt memory deficits. Neurobiol Dis 54:372-381. doi: 10.1016/j.nbd.2013.01.010

Summary: The authors examined whether partial degeneration of septo-hippocampal neurons alters brain activity patterns even without overt memory loss. Mice received 45 ng of mu p75-SAP (Cat. #IT-16) into the medial septal area. Lesioned animals had significantly altered functional activities in the brain, despite lack of an overt behavioral deficit. Some changes observed are also altered with the initial signs of Alzheimer’s disease.

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

Szigeti C, Bencsik N, Simonka AJ, Legradi A, Kasa P, Gulya K (2013) Long-term effects of selective immunolesions of cholinergic neurons of the nucleus basalis magnocellularis on the ascending cholinergic pathways in the rat: A model for Alzheimer’s disease. Brain Res Bull 94C:9-16. doi: 10.1016/j.brainresbull.2013.01.007

Summary: 192-IgG-SAP (Cat. #IT-01) has been used extensively to generate models of Alzheimer’s disease in rats. In this work, the authors detailed the time course of neuronal loss with an eye on potential recovery from the lesion. The nucleus basalis magnocellularis of rats was injected with 75 ng of 192-IgG-SAP (Cat. #IT-01) and long-term changes were tracked by immunohistochemistry. While some acetylcholinesterase neurons, considered cholinoceptive, were lost, choline acetyltransferase (cholinergic) neurons sustained a massive irreversible reduction in number.

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

Hamlin AS, Windels F, Boskovic Z, Sah P, Coulson EJ (2013) Lesions of the basal forebrain cholinergic system in mice disrupt idiothetic navigation. PLoS One 8(1):e53472. doi: 10.1371/journal.pone.0053472

Summary: Alzheimer’s disease patients perform poorly on spatial navigation tests requiring either distal cues (allothetic) or body-centered cues (idiothetic). The authors used 0.2 μg bilateral infusions of mu p75-SAP (Cat. #IT-16) into the lateral ventricles of mice to examine the hypothesis that the cholinergic medial septo-hippocampal circuit is important for idiothetic navigation. Rabbit IgG-SAP (Cat. #IT-35) was used as a control. Lesioned animals were similar to controls in contextual fear conditioning, spatial working memory, as well as several other parameters. But exploratory behavior requiring idiothetic signals was very disorganized, indicating that cholinergic cells are vital to idiothetic navigation.

Related Products: mu p75-SAP (Cat. #IT-16), Rabbit IgG-SAP (Cat. #IT-35)