CTBP1 Confers Protection for Hippocampal and Cortical Neurons in Rat Models of Alzheimer's Disease.

Abstract

OBJECTIVE:

Alzheimer's disease (AD) is an age-related devastating neurodegenerative disorder. The hippocampus and cerebral cortex are the most closely related brain regions of cognitive function and neurogenesis. The present study investigated the role of C-terminal-binding protein 1 (CTBP1) in AD.

METHODS:

AD rat models were established through intracerebroventricular injection of β-amyloid polypeptide Aβ(25-35) and intragastric administration of aluminum chloride solution, and the expression pattern that CTBP1 showed in the hippocampus and cerebral cortex was determined. The learning and memory abilities of AD rats after CTBP1 overexpression were assessed. Hippocampal and cortical neurons were transfected with siRNA against CTBP1 or CTBP1-overexpressing plasmids in order to study the effects of CTBP1 elevation or depletion on neuron morphological changes, apoptosis, and viability. The expression of CTBP1, proapoptotic factor (B-cell lymphoma 2; Bcl-2), and antiapoptotic factors (Bcl-2-associated X protein [Bax] and caspase-3) was subsequently evaluated.

RESULTS:

CTBP1 was poorly expressed in the hippocampus and cerebral cortex. AD rats displayed enhanced learning and memory abilities following CTBP1 overexpression. Furthermore, overexpression of CTBP1 improved morphological changes of hippocampal and cortical neurons, increased neuron activity, and inhibited neuron apoptosis in AD rats. Moreover, the expression of Bax and caspase-3 decreased, yet Bcl-2 increased.

CONCLUSION:

Collectively, CTBP1 plays a protective role in the degeneration of hippocampal and cortical neurons whereby overexpressed CTBP1 attenuated the hippocampal and cortical neuron apoptosis and enhanced neuron activity, highlighting the potential of CTBP1 as a target for AD treatment.

• Authors: Kai Hu, Yafeng Li, Huifen Yu, Yanhui Hu
• Journal: Neuroimmunomodulation (Neuroimmunomodulation) Vol. 26 Issue 3 Pg. 139-152 ( 2019) ISSN: 1423-0216 [Electronic] Switzerland
• PMID: 31340205 (Publication Type: Journal Article)
• Copyright: © 2019 S. Karger AG, Basel.

Chemical References

• Carrier Proteins
• Ctbp1 protein, rat
• Transcription Factors

Topics

• Alzheimer Disease (metabolism, pathology)
• Animals
• Apoptosis (physiology)
• Carrier Proteins (metabolism)
• Cerebral Cortex (metabolism, pathology)
• Disease Models, Animal
• Female
• Hippocampus (metabolism, pathology)
• Neurons (metabolism, pathology)
• Rats
• Rats, Sprague-Dawley
• Transcription Factors (metabolism)