Astrocytes play key roles in the brain. When astrocyte support fails, neurological disorders follow, resulting in disrupted synaptic communication, neuronal degeneration, and cell death. We posit that astrocytes overexpressing neurotrophic factors, such as Insulin Like Growth Factor 1 (IGF1), prevent the onset of neurodegeneration. We overexpressed IGF1 and the reporter TdTomato (TOM) in hippocampal astrocytes with bicistronic Adeno-Associated Virus (AAV) harboring the Glial Fibrillary Acidic Protein (GFAP) promoter and afterwards induced neurodegeneration by the intracerebroventricular (ICV) injection of streptozotocin (STZ), a rat model of behavioral impairment, neuroinflammation and shortening of hippocampal astrocytes. We achieved a thorough transgene expression along the hippocampus with a single viral injection. Although species typical behavior was impaired, memory deficit was prevented by IGF1. STZ prompted astrocyte shortening, albeit the length of these cells in animals injected with GFP and IGF1 vectors did not statistically differ from the other groups. In STZ control animals, hippocampal microglial reactive cells increased dramatically, but this was alleviated in IGF1 rats. We conclude that overexpression of IGF1 in astrocytes prevents neurodegeneration onset. Hence, individuals with early neurotrophic exhaustion would be vulnerable to age-related neurodegeneration.
Keyphrases
- cerebral ischemia
- diabetic rats
- binding protein
- pi k akt
- growth hormone
- cell cycle arrest
- cell death
- induced apoptosis
- oxidative stress
- gene therapy
- subarachnoid hemorrhage
- transcription factor
- dna methylation
- blood brain barrier
- brain injury
- gene expression
- type diabetes
- inflammatory response
- traumatic brain injury
- spinal cord injury
- resting state
- multiple sclerosis
- white matter
- working memory
- lps induced
- endoplasmic reticulum stress
- endothelial cells
- mouse model
- high glucose
- amino acid