Deep brain stimulation facilitates memory in a model of Alzheimer’s disease

Walter de Gruyter GmbH - 2010
Isabel Arrieta‐Cruz1, Constantine Pavlides2, Giulio Maria Pasinetti
1Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA
2Laboratory of Neuroendocrinology, Rockefeller University, 1230 York Avenue, New York, NY, 10065, USA

Tóm tắt

AbstractBased on evidence suggesting that deep brain stimulation (DBS) may promote certain cognitive processes, we have been interested in developing DBS as a means of mitigating memory and learning impairments in Alzheimer’s disease (AD). In this study we used an animal model of AD (TgCRND8 mice) to determine the effects of high-frequency stimulation (HFS) on non-amyloidogenic α-secretase activity and DBS in short-term memory. We tested our hypothesis using hippocampal slices (in vitro studies) from TgCRND8 mice to evaluate whether HFS increases α-secretase activity (non-amyloidogenic pathway) in the CA1 region. In a second set of experiments, we performed in vivo studies to evaluate whether DBS in midline thalamic region re-establishes hippocampal dependent short-term memory in TgCRND8 mice. The results showed that application of HFS to isolated hippocampal slices significantly increased synaptic plasticity in the CA1 region and promoted a 2-fold increase of non-amyloidogenic α-secretase activity, in comparison to low frequency stimulated controls from TgCRND8 mice. In the in vivo studies, DBS treatment facilitated acquisition memory in TgCRND8 mice, in comparison to their own baseline before treatment. These results provide evidence that DBS could enhance short-term memory in a mouse model of AD by increasing synaptic transmission and α-secretase activity in the CA1 region of hippocampus.

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Tài liệu tham khảo

Kringelbach ML, Jenkinson N, Owen S, Aziz TZ, Translational principles of deep brain stimulation, Nature Rev Neuroscience, 8 (2007) 623–635.

Hu R, Eskandar E, Williams Z, Role of deep brain stimulation in modulating memory formation and recall, Neurosurg Focus 27 (2009) 1–5.

Shirvalkar P, Seth M, Schiff ND, Herrera DG, Cognitive enhancement with central thalamic electrical stimulation, Proc Natl Acad Sci U S A, 103 (2006) 17007–17012.

Paxinos G, Franklin K BJ, The Mouse Brain in Stereotaxic Coordinates, Second edition, (2001) Academic Press.

Mitchell AS, Dalrymple-Alford JC, Lateral and anterior thalamic lesions impair independent memory systems, Learn Mem, 13 (2006) 388–396.

Arrieta I, Díaz-Ibáñez LB, Morales T, Mendoza-Garcés L, Morimoto S, Moreno-Mendoza N, Cerbón MA, Progesterone receptor gene and protein expression in the anterior preoptic area and hypothalamus of defeminized rats. J Neurobiol, 56 (2003) 338–346.

Bellucci A, Luccarini I, Scali C, Prosperi C, Giovannini MG, Pepeu G, Casamenti F, Cholinergic dysfunction, neuronal damage and axonal loss in TgCRND8 mice. Neurobiol Dis 23 (2006) 260–272.

Ye H, Jalini S, Mylvaganam S, Carlen P, Activation of largeconductance Ca(2+)-activated K(+) channels depresses basal synaptic transmission in the hippocampal CA1 area in APP (swe/ind) TgCRND8 mice. Neurobiol. Aging. doi:10.1016/j.neurobiolaging.2008.05.012

Steriade M, in Thalamus eds. Steriade M, Jones E, McCormick D. Elsevier, Amsterdam (1997) 721–742.

Schiff ND, Purpura, KP, Towards a neurophysiological foundation for cognitive neuromodulation through deep brain stimulation. Thalamus and Related Systems 2 (2002) 55–69.

Farber SA, Nitsch RM, Schulz JG, Wurtman RJ, Regulated secretion of beta-amyloid precursor protein in rat brain, J Neurosci, 15 (1995) 7442–7451.

Laird FM, Cai H, Savonenko AV, Farah MH, He K, Melnikova T, Wen H, Chiang HC, Xu G, Koliatsos VE, Borchelt DR, Price DL, Lee HK, Wong PC, BACE1, a major determinant of selective vulnerability of the brain to amyloid-beta amyloidogenesis, is essential for cognitive, emotional, and synaptic functions, J Neurosci, 25 (2005) 11693–11709.

Chishti MA, Yang DS, Janus C, Phinney AL, Horne P, Pearson J, Strome R, Zuker N, Loukides J, French J, Turner S, Lozza G, Grilli M, Kunicki S, Morissette C, Paquette J, Gervais F, Bergeron C, Fraser PE, Carlson GA, George-Hyslop PS, Westaway D, Early-onset amyloid deposition and cognitive deficits in transgenic mice expressing a double mutant form of amyloid precursor protein 695, J Biol Chem, 276 (2001) 21562–21570.

Chapman PF, White GL., Jones MW, Cooper-Blacketer D, Marshall VJ, Irizarry., Younkin L, Good MA, Bliss TV, Hyman BT, Younkin SG, Hsiao KK, Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice, Nat Neurosci, 2 (1999) 271–276.

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