scholarly journals Alzheimer’s Disease Mouse as a Model of Testis Degeneration

2020 ◽  
Vol 21 (16) ◽  
pp. 5726
Author(s):  
Vince Szegeczki ◽  
Gabriella Horváth ◽  
Helga Perényi ◽  
Andrea Tamás ◽  
Zsolt Radák ◽  
...  
Keyword(s):  
Physical Activity ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cell Number ◽  
Negative Effects ◽  
Signaling Mechanism ◽  
Peripheral Organs ◽  
Type Iv ◽  
Model Of Alzheimer’S Disease ◽  
The Central Nervous System

Pituitary adenylate cyclase activating polypeptide (PACAP) is a neuropeptide with protective functions in the central nervous system and various peripheral organs. PACAP has the highest expression level in the testes, among the peripheral organs, and has a positive regulative role in spermatogenesis and in sperm motility. In the present study, we explored testicular degenerative alterations in a mouse model of Alzheimer’s disease (AD) (B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J) and demonstrated changes in PACAP-regulated signaling pathways. In addition, the effects of increased physical activity of AD (trained AD (TAD)) mice on testis were also followed. Reduced cell number and decreased thickness of basement membrane were detected in AD samples. These changes were compensated by physical activity. Expression of PACAP receptors and canonical signaling elements such as PKA, P-PKA, PP2A significantly decreased in AD mice, and altered Sox transcription factor expression was also detected. Via this signaling mechanism, physical activity compensated the negative effects of AD on the expression of type IV collagen. Our findings suggest that the testes of AD mice can be a good model of testis degeneration. Moreover, it can be an appropriate organ to follow the effects of various interventions such as physical activity on tissue regeneration and signaling alterations.

scholarly journals Fingolimod Rescues Memory and Improves Pathological Hallmarks in the 3xTg-AD Model of Alzheimer’s Disease

2022 ◽  
Author(s):  
Steven G. Fagan ◽  
Sibylle Bechet ◽  
Kumlesh K. Dev
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Biochemical Analysis ◽  
Spatial Working Memory ◽  
Cell Number ◽  
Model Of Alzheimer’S Disease ◽  
Candidate Drug ◽  
Inflammatory Processes ◽  
The Brain ◽  
Ad Mouse Model

AbstractTherapeutic strategies for Alzheimer’s disease (AD) have largely focused on the regulation of amyloid pathology while those targeting tau pathology, and inflammatory mechanisms are less explored. In this regard, drugs with multimodal and concurrent targeting of Aβ, tau, and inflammatory processes may offer advantages. Here, we investigate one such candidate drug in the triple transgenic 3xTg-AD mouse model of AD, namely the disease-modifying oral neuroimmunomodulatory therapeutic used in patients with multiple sclerosis, called fingolimod. In this study, administration of fingolimod was initiated after behavioral symptoms are known to emerge, at 6 months of age. Treatment continued to 12 months when behavioral tests were performed and thereafter histological and biochemical analysis was conducted on postmortem tissue. The results demonstrate that fingolimod reverses deficits in spatial working memory at 8 and 12 months of age as measured by novel object location and Morris water maze tests. Inflammation in the brain is alleviated as demonstrated by reduced Iba1-positive and CD3-positive cell number, less ramified microglial morphology, and improved cytokine profile. Finally, treatment with fingolimod was shown to reduce phosphorylated tau and APP levels in the hippocampus and cortex. These results highlight the potential of fingolimod as a multimodal therapeutic for the treatment of AD.

scholarly journals Revisiting the Radiosynthesis of [18F]FPEB and Preliminary PET Imaging in a Mouse Model of Alzheimer’s Disease

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 982
Author(s):  
Cassis Varlow ◽  
Emily Murrell ◽  
Jason P. Holland ◽  
Alina Kassenbrock ◽  
Whitney Shannon ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Radiochemical Yield ◽  
Sulfonium Salt ◽  
Model Of Alzheimer’S Disease ◽  
Positron Emission ◽  
The Central Nervous System ◽  
Early Biomarker ◽  
Pet Radiopharmaceutical ◽  
Abundance And Distribution

[18F]FPEB is a positron emission tomography (PET) radiopharmaceutical used for imaging the abundance and distribution of mGluR5 in the central nervous system (CNS). Efficient radiolabeling of the aromatic ring of [18F]FPEB has been an ongoing challenge. Herein, five metal-free precursors for the radiofluorination of [18F]FPEB were compared, namely, a chloro-, nitro-, sulfonium salt, and two spirocyclic iodonium ylide (SCIDY) precursors bearing a cyclopentyl (SPI5) and a new adamantyl (SPIAd) auxiliary. The chloro- and nitro-precursors resulted in a low radiochemical yield (<10% RCY), whereas both SCIDY precursors and the sulfonium salt precursor produced [18F]FPEB in the highest RCYs of 25% and 36%, respectively. Preliminary PET/CT imaging studies with [18F]FPEB were conducted in a transgenic model of Alzheimer’s Disease (AD) using B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J (APP/PS1) mice, and data were compared with age-matched wild-type (WT) B6C3F1/J control mice. In APP/PS1 mice, whole brain distribution at 5 min post-injection showed a slightly higher uptake (SUV = 4.8 ± 0.4) than in age-matched controls (SUV = 4.0 ± 0.2). Further studies to explore mGluR5 as an early biomarker for AD are underway.

scholarly journals Physical Activity Ameliorates Impaired Hippocampal Neurogenesis in the Tg4-42 Mouse Model of Alzheimer’s Disease

ASN NEURO ◽  
2019 ◽  
Vol 11 ◽  
pp. 175909141989269 ◽  
Author(s):  
Anna-Lina Gerberding ◽  
Silvia Zampar ◽  
Martina Stazi ◽  
David Liebetanz ◽  
Oliver Wirths
Keyword(s):  
Physical Activity ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Dentate Gyrus ◽  
Structural Changes ◽  
Hippocampal Neurogenesis ◽  
Wild Type ◽  
Running Wheel ◽  
Model Of Alzheimer’S Disease

There is growing evidence from epidemiological studies that especially midlife physical activity might exert a positive influence on the risk and progression of Alzheimer’s disease. In this study, the Tg4-42 mouse model of Alzheimer’s disease has been utilized to assess the effect of different housing conditions on structural changes in the hippocampus. Focusing on the dentate gyrus, we demonstrate that 6-month-old Tg4-42 mice have a reduced number of newborn neurons in comparison to age-matched wild-type mice. Housing these mice for 4 months with either unlimited or intermittent access to a running wheel resulted in a significant rescue of dentate gyrus neurogenesis. Although neither dentate gyrus volume nor neuron number could be modified in this Alzheimer’s disease mouse model, unrestricted access to a running wheel significantly increased dentate gyrus volume and granule cell number in wild-type mice.

scholarly journals Effects of Terpinolene and Physical Activity on Memory and Learning in a Model of Alzheimer's Disease among Rats

2020 ◽  
Vol 14 (10) ◽  
pp. 25-33
Author(s):  
Bahareh Seifi Nahavandi ◽  
Parichehreh Yaghmaei ◽  
Shahin Ahmadian ◽  
Azadeh Ebrahim-Habibi ◽  
Maryam Ghobeh ◽  
...  
Keyword(s):  
Physical Activity ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Memory And Learning ◽  
Model Of Alzheimer’S Disease

Paired helical filaments (PHF) in rats: An experimental animal model for Alzheimer's disease

1987 ◽  
Vol 45 ◽  
pp. 842-843
Author(s):  
V.J.A. Montpetit ◽  
S. Dancea ◽  
S.W. French ◽  
D.F. Clapin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Animal Model ◽  
Paired Helical Filaments ◽  
Ethanol Intoxication ◽  
Drg Neurons ◽  
Critical Difference ◽  
Suitable Animal Model ◽  
The Central Nervous System ◽  
Chronic Ethanol Intoxication

A continuing problem in Alzheimer research is the lack of a suitable animal model for the disease. The absence of neurofibrillary tangles of paired helical filaments is the most critical difference in the processes by which the central nervous system ages in most species other than man. However, restricting consideration to single phenomena, one may identify animal models for specific aspects of Alzheimer's disease. Abnormal fibers resembling PHF have been observed in dorsal root ganglia (DRG) neurons of rats in a study of chronic ethanol intoxication and spontaneously in aged rats. We present in this report evidence that PHF-like filaments occur in ethanol-treated rats of young age. In control animals lesions similar in some respects to our observations of cytoskeletal pathology in pyridoxine induced neurotoxicity were observed.Male Wistar BR rats (Charles River Labs) weighing 350 to 400 g, were implanted with a single gastrostomy cannula and infused with a liquid diet containing 30% of total calories as fat plus ethanol or isocaloric dextrose.

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