Mouse models of neurodegenerative disease: preclinical imaging and neurovascular component

Abstract

Neurodegenerative diseases represent great challenges for basic science and clinical medicine because of their prevalence, pathologies, lack of mechanism-based treatments, and impacts on individuals. Translational research might contribute to the study of neurodegenerative diseases. The mouse has become a key model for studying disease mechanisms that might recapitulate in part some aspects of the corresponding human diseases. Neurodegenerative disorders are very complicated and multifactorial. This has to be taken in account when testing drugs. Most of the drugs screening in mice are very difficult to be interpretated and often useless. Mouse models could be condiderated a 'pathway models', rather than as models for the whole complicated construct that makes a human disease. Non-invasive in vivo imaging in mice has gained increasing interest in preclinical research in the last years thanks to the availability of high-resolution single-photon emission computed tomography (SPECT), positron emission tomography (PET), high field Magnetic resonance, Optical Imaging scanners and of highly specific contrast agents. Behavioral test are useful tool to characterize different animal models of neurodegenerative pathology. Furthermore, many authors have observed vascular pathological features associated to the different neurodegenerative disorders. Aim of this review is to focus on the different existing animal models of neurodegenerative disorders, describe behavioral tests and preclinical imaging techniques used for diagnose and describe the vascular pathological features associated to these diseases.

Diffusion Tensor Imaging-Based Studies at the Group-Level Applied to Animal Models of Neurodegenerative Diseases

“…Animal studies have a crucial role in neuroscience and have substantially contributed to the understanding of neurodegeneration, and the studies previously presented in the various models of different neurodegenerative disease will pave the way for further DTI-based imaging read-outs in animals, including tracking of changes associated with pharmacological manipulation. Although animal studies are not a substitute for studies in real human biology, animal models provide opportunities for experiments that cannot be performed in humans and thus represent a critical platform upon which translational efforts for treating human neurodegenerative diseases are built (Albanese et al, 2018 ). Since advanced genetic techniques allow the manipulation of the genome and precise control of gene expression in rodents, transgenic models of human neuropathology are becoming increasingly important.…”

Experimental Models in Neurodegenerative Diseases

“…Genel olarak, erken dönem değişiklikleri görüntülemek için kullanışlı olan yöntemler, tek foton emisyonlu bilgisayarlı tomografi (SPECT), PET ve MRG gibi fonksiyonel görüntüleme yöntemleridir. Günümüzde yaygın olarak kullanılan hibrid sistemler [SPECT/bilgisayarlı tomografi (BT), PET/BT ve PET/MRG], anatomik ve fonksiyonel görüntülemeyi birleştirerek çok daha verimli sonuçlar sunmaktadır (54).…”

“…MRG sistemleri ise, plak oluşumları ve nörodejenerasyona bağlı atrofik alanları saptamada öne çıkmaktadır. Fonksiyonel MRG ile beyin kan akımı da verimli biçimde takip edilebilir (54).…”

“…Beyin fonksiyonunun biyolojik belirteci olan beyin metabolizmasını sayısal olarak ölçmek için, MRG spektroskopisi tercih edilen yöntemdir. Spektroskopik olarak glutamaterjik, GABAerjik ve astroglial fonksiyonlarını değerlendirmek için (1,6-3C2) glukoz veya (2-13C) asetat enfüzyonu kullanılabilir (54).…”

“…Bu radyo işaretleyicinin çok hızlı metabolize olması nedeniyle, transgenik farelerde dopaminerjik değişiklikleri izleyebilmek için uzun yarı ömürlü bir VMAT2 ligandı olan F18-dihidrotetrabenzin kullanılmaktadır. Bunun dışında 2β-karbometoksi-3β-(4-klorofenil)-8-(2-[F-18]-floroetil)-nortropan da, insanlar ve maymunlarda dopaminerjik sistemi değerlendirmede başarılıdır (54).…”