PMID- 22327870 OWN - NLM STAT- MEDLINE DCOM- 20121023 LR - 20211021 IS - 1660-2862 (Electronic) IS - 1660-2854 (Print) IS - 1660-2854 (Linking) VI - 9 IP - 4 DP - 2012 TI - Evaluation of neurodegeneration in a mouse model of infantile batten disease by magnetic resonance imaging and magnetic resonance spectroscopy. PG - 159-69 LID - 10.1159/000334838 [doi] AB - Neuronal ceroid lipofuscinoses (NCLs) represent a group of common hereditary childhood neurodegenerative storage disorders that have no effective treatment. Mutations in eight different genes cause various forms of NCLs. Infantile NCL (INCL), the most lethal disease, is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. The availability of Ppt1-knockout (Ppt1-KO) mice, which recapitulate virtually all clinical and pathological features of INCL, provides an opportunity to test the effectiveness of novel therapeutic strategies in vivo. However, such studies will require noninvasive methods that can be used to perform serial evaluations of the same animal receiving an experimental therapy. Thus, the development of noninvasive method(s) of evaluation is urgently needed. Here, we report our evaluation of the progression of neurodegeneration in Ppt1-KO mice starting at 3 months of age by MRI and MR spectroscopy (MRS) and repeating these tests using the same mice at 4, 5 and 6 months of age. Our results showed progressive cerebral atrophy, which was associated with histological loss of neuronal content and increase in astroglia. Remarkably, while the brain volumes in Ppt1-KO mice progressively declined with advancing age, the MRS signals, which were significantly lower than those of their wild-type littermates, remained virtually unchanged from 3 to 6 months of age. In addition, our results also showed an abnormality in cerebral blood flow in these mice, which showed progression with age. Our findings provide methods to serially examine the brains of mouse models of neurodegenerative diseases (e.g. Ppt1-KO mice) using noninvasive and nonlethal procedures such as MRI and MRS. These methods may be useful in studies to understand the progression of neuropathology in animal models of neurodegenerative diseases as they allow repeated evaluations of the same animal in which experimental therapies are tested. CI - Copyright (c) 2012 S. Karger AG, Basel. FAU - Munasinghe, Jeeva AU - Munasinghe J AD - In Vivo NMR Center-HNQ2-3, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1830, USA. mukherja@exchange.nih.gov FAU - Zhang, Zhongjian AU - Zhang Z FAU - Kong, Eryan AU - Kong E FAU - Heffer, Alison AU - Heffer A FAU - Mukherjee, Anil B AU - Mukherjee AB LA - eng GR - Intramural NIH HHS/United States PT - Evaluation Study PT - Journal Article PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20120209 PL - Switzerland TA - Neurodegener Dis JT - Neuro-degenerative diseases JID - 101189034 RN - EC 3.1.2.- (Thiolester Hydrolases) RN - EC 3.1.2.22 (palmitoyl-protein thioesterase) SB - IM MH - Aging/pathology MH - Animals MH - Astrocytes/pathology MH - Brain/pathology MH - Disease Models, Animal MH - *Disease Progression MH - Female MH - Magnetic Resonance Imaging/*methods MH - Magnetic Resonance Spectroscopy/*methods MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Neurodegenerative Diseases/*diagnosis/genetics/*pathology MH - Neuronal Ceroid-Lipofuscinoses/*diagnosis/genetics/*pathology MH - Neurons/pathology MH - Organ Size MH - Thiolester Hydrolases/deficiency/genetics PMC - PMC3369263 EDAT- 2012/02/14 06:00 MHDA- 2012/10/24 06:00 PMCR- 2013/05/01 CRDT- 2012/02/14 06:00 PHST- 2011/07/19 00:00 [received] PHST- 2011/10/31 00:00 [accepted] PHST- 2012/02/14 06:00 [entrez] PHST- 2012/02/14 06:00 [pubmed] PHST- 2012/10/24 06:00 [medline] PHST- 2013/05/01 00:00 [pmc-release] AID - 000334838 [pii] AID - ndd-0009-0159 [pii] AID - 10.1159/000334838 [doi] PST - ppublish SO - Neurodegener Dis. 2012;9(4):159-69. doi: 10.1159/000334838. Epub 2012 Feb 9.