PhD Scientific Days 2019

Budapest, April 25–26, 2019

Amyloid-beta alone induces changes in hippocampal gabaergic synapses

Mayer, Márton

Márton I. Mayer1, Katalin E. Sos1, Virág T. Takács1, Ábel Major1, Zsuzsanna Bardóczi1, Barnabas Béres1, Tamás Szeles1, Takaomi C. Saido2, Takashi Saito2, Tamás F. Freund1, Gábor Nyiri1
1 Department of Cellular and Network Neurobiology, Institute of Experimental Medicine, Budapest
2 RIKEN Brain Science Institute, Laboratory for Proteolytic Neuroscience, Wako, Japan

Language of the presentation

English

Text of the abstract

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder, characterized partly by amyloid-beta (Aβ) depositions in cortical areas. Several transgenic mouse lines were created to examine the effect of Aβ, however, most of them employed strong non-specific promoters to drive Aβ expression.

Method: We used APP-NL-F mice that are unique, as they express Aβ driven by the natural promoter of amyloid precursor protein (APP), the latter of which is a mutated version of the human APP in this strain.

Aims: We investigated subcellular effects of Aβ in the hippocampus of APP-NL-F mice.

Results: We found that Aβ alone caused typical plaque formation, glial activation and malformation of neurites. It induced the formation of significantly larger synapses on axon initial segments of pyramidal cells and caused impairment in natural anxiety in the elevated plus maze. However, these mice lack some changes typical in AD model animals, including the degeneration of septo-hippocampal cholinergic and parvalbumin positive pathways and changes in the number of hippocampal parvalbumin and somatostatin positive interneurons.

Conclusion: These results suggest that upregulation of Aβ expression alone can induce changes in the inhibitory balance of hippocampal pyramidal cells, which may contribute to disease progression during the preclinical phase of AD.

Data of the presenter

Doctoral School: János Szentágothai Doctoral School of Neurosciences
Program: Neuromorphology and Cell Biology
Supervisor: Dr. Gábor Nyiri
E-mail address: mayer.marton@koki.mta.hu