Examination of Longitudinal Alterations in Alzheimer's Disease-Related Neurogenesis in an APP/PS1 Transgenic Mouse Model, and the Effects of P33, a Putative Neuroprotective Agent Thereon.
Titanilla SzögiEmőke BorbélyIldikó SchusterZsolt BozsóMiklós SánthaMelinda E TóthBotond PenkeLivia FulopPublished in: International journal of molecular sciences (2022)
Neurogenesis plays a crucial role in cognitive processes. During aging and in Alzheimer's disease (AD), altered neurogenesis and neuroinflammation are evident both in C57BL/6J, APP Swe /PS1 dE9 (Tg) mice and humans. AD pathology may slow down upon drug treatment, for example, in a previous study of our group P33, a putative neuroprotective agent was found to exert advantageous effects on the elevated levels of APP, Aβ, and neuroinflammation. In the present study, we aimed to examine longitudinal alterations in neurogenesis, neuroinflammation and AD pathology in a transgenic (Tg) mouse model, and assessed the putative beneficial effects of long-term P33 treatment on AD-specific neurological alterations. Hippocampal cell proliferation and differentiation were significantly reduced between 8 and 12 months of age. Regarding neuroinflammation, significantly elevated astrogliosis and microglial activation were observed in 6- to 7-month-old Tg animals. The amounts of the molecules involved in the amyloidogenic pathway were altered from 4 months of age in Tg animals. P33-treatment led to significantly increased neurogenesis in 9-month-old animals. Our data support the hypothesis that altered neurogenesis may be a consequence of AD pathology. Based on our findings in the transgenic animal model, early pharmacological treatment before the manifestation of AD symptoms might ameliorate neurological decline.
Keyphrases
- cerebral ischemia
- cell proliferation
- mouse model
- subarachnoid hemorrhage
- traumatic brain injury
- lipopolysaccharide induced
- brain injury
- lps induced
- blood brain barrier
- cognitive impairment
- inflammatory response
- type diabetes
- cross sectional
- metabolic syndrome
- spinal cord injury
- machine learning
- cognitive decline
- emergency department
- signaling pathway
- artificial intelligence
- sleep quality
- replacement therapy
- smoking cessation
- adverse drug