alzheimers-disease

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)

Kerbler GM, Hamlin AS, Pannek K, Kurniawan ND, Keller MD, Rose SE, Coulson EJ (2013) Diffusion-weighted magnetic resonance imaging detection of basal forebrain cholinergic degeneration in a mouse model. Neuroimage 66C:133-141. doi: 10.1016/j.neuroimage.2012.10.075

Summary: The authors examined the effectiveness of diffusion MRI using diffusion tensor imaging (DTI) and probabilistic tractography in detecting cholinergic loss in a mouse model. Mice received bilateral 0.2-μg icv injections of mu p75-SAP (Cat. #IT-16). Rabbit IgG-SAP (Cat. #IT-35) was used as control. The animals were then examined using DTI. The data indicate that DTI is a valid technique for assessment of cholinergic loss in septo-hippocampal tracts as a result of Alzheimer’s disease.

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

Ortiz-Barajas O, Ramos-Rodriguez J, Berrocoso E, Garcia Alloza M (2012) Limited effect of serotonergic denervation on beta-amyloid and cognitive impairment in APPswe/PS1dE9 mice. Neuroscience 2012 Abstracts 751.12. Society for Neuroscience, New Orleans, LA.

Summary: Alzheimer’s Disease (AD) is a neurodegenerative disease characterized by progressive cognitive and memory impairment. Amyloid-beta (Aβ) deposition, as senile plaques (SP), seems to play a key role in the development and progression of the illness. Moreover SP tend to accumulate in cortex and hippocampus, relevant areas in learning and memory. On the other hand neuronal loss is the pathological feature that best correlates with duration and severity of the illness and at present animal available animal models hardly reproduce the complexity of the disease. We have previously seen that selective cortical and hipocampal cholinergic denervation, using murine p-75 saporin, may worsen cognitive abilities in APPswe/PS1dE9 mice as well as increase SP deposition in denervated areas. In the present work we lesioned 7 months old APPswe/PS1dE9 mice with 1 µl of 5,7-dyhidroxytiptamine (0.16 µg/µl) injected in the raphe nucleus (RN). In order to guarantee selective removal of cortical and hipocampal serotonergic inervation, and protect noardernergic and dopaminergic neurons, animals were i.p. injected with desipramine and nomifensine before surgery. We observed a clear reduction of tryptophan hydroxilase staining in the RN. In the Morris water maze test we observed learning and memory impairment in APPswe/Ps1dE9 mice, without a synergistic effect of the serotonergic lesion. When we assessed SP deposition we did not observe a significant increase of SP in cortex or hipocampus 14 days after the lesion, as we observed after selective cholinergic denervation. Altogether our data suggest that cognitive impairment and induced SP depositioin observed after cholinergic denervation is not achieved when serotonergic system is affected, supporting a selective effect mediated by different neurotransmitter systems. Acknowledgements: MG-A: RYC-2008-02333, ISCIII-Subdirección General de Evaluación y Fomento de la Investigación (PS09/00969), Fundación Dr. Eugenio Rodriguez Pascual, Junta Andalucia Excelencia (CTS-7847).

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