caa a22 4500 606203079 CHVBK 20210128100956.0 cr unu---uuuuu 210128e20150901xx s 000 0 eng 10.1007/s00429-014-0839-0 doi (NATIONALLICENCE)springer-10.1007/s00429-014-0839-0 Expression profile analysis of hippocampal CA1 pyramidal neurons in aged Ts65Dn mice, a model of Down syndrome (DS) and Alzheimer's disease (AD) [Elektronische Daten] [Melissa Alldred, Sang Lee, Eva Petkova, Stephen Ginsberg] Down syndrome (DS) is caused by the triplication of human chromosome 21 (HSA21) and is the most common genetic cause of intellectual disability, with individuals having deficits in cognitive function including hippocampal learning and memory and neurodegeneration of cholinergic basal forebrain neurons, a pathological hallmark of Alzheimer's disease (AD). To date, the molecular underpinnings driving this pathology have not been elucidated. The Ts65Dn mouse is a segmental trisomy model of DS and like DS/AD pathology, displays age-related cognitive dysfunction and basal forebrain cholinergic neuron (BFCN) degeneration. To determine molecular and cellular changes important for elucidating mechanisms of neurodegeneration in DS/AD pathology, expression profiling studies were performed. Molecular fingerprinting of homogeneous populations of Cornu Ammonis 1 (CA1) pyramidal neurons was performed via laser capture microdissection followed by Terminal Continuation RNA amplification combined with custom-designed microarray analysis and subsequent validation of individual transcripts by qPCR and protein analysis via immunoblotting. Significant alterations were observed within CA1 pyramidal neurons of aged Ts65Dn mice compared to normal disomic (2N) littermates, notably in excitatory and inhibitory neurotransmission receptor families and neurotrophins, including brain-derived neurotrophic factor as well as several cognate neurotrophin receptors. Examining gene and protein expression levels after the onset of BFCN degeneration elucidated transcriptional and translational changes in neurons within a vulnerable circuit that may cause the AD-like pathology seen in DS as these individuals age, and provide rational targets for therapeutic interventions. Springer-Verlag Berlin Heidelberg, 2014 Alzheimer's disease nationallicence BDNF nationallicence Down syndrome nationallicence Glutamatergic neurotransmission nationallicence Hippocampus nationallicence Laser capture microdissection nationallicence Murine model nationallicence Neurotrophin nationallicence Alldred Melissa Center for Dementia Research, Nathan Kline Institute, 140 Old Orangeburg Road, 10962, Orangeburg, NY, USA aut Lee Sang Division of Medical Physics, Nathan Kline Institute, Orangeburg, NY, USA aut Petkova Eva Division of Child Psychiatry, Nathan Kline Institute, Orangeburg, NY, USA aut Ginsberg Stephen Center for Dementia Research, Nathan Kline Institute, 140 Old Orangeburg Road, 10962, Orangeburg, NY, USA aut Brain Structure and Function Springer Berlin Heidelberg 220/5(2015-09-01), 2983-2996 1863-2653 220:5<2983 2015 220 429 https://doi.org/10.1007/s00429-014-0839-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00429-014-0839-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Alldred Melissa Center for Dementia Research, Nathan Kline Institute, 140 Old Orangeburg Road, 10962, Orangeburg, NY, USA aut NATIONALLICENCE 700 1- Lee Sang Division of Medical Physics, Nathan Kline Institute, Orangeburg, NY, USA aut NATIONALLICENCE 700 1- Petkova Eva Division of Child Psychiatry, Nathan Kline Institute, Orangeburg, NY, USA aut NATIONALLICENCE 700 1- Ginsberg Stephen Center for Dementia Research, Nathan Kline Institute, 140 Old Orangeburg Road, 10962, Orangeburg, NY, USA aut NATIONALLICENCE 773 0- Brain Structure and Function Springer Berlin Heidelberg 220/5(2015-09-01), 2983-2996 1863-2653 220:5<2983 2015 220 429