University of Eastern Finland
A. I. Virtanen Institute
Heikki Tanila is Professor of Translational Neuroscience at A. I. Virtanen Institute, Univ. Eastern Finland in Kuopio, Finland, since 2005 and at present also the Director of the Institute. He got his MD in 1988 and PhD in 1993 at Univ. Helsinki, Finland. He did his post-doctoral fellowship at SUNY at Stony Brook, NY, USA in the laboratory of prof. Howard Eichenbaum during 1993-1995 and was a visiting scientist at The Picower Institute, MIT, Cambridge, MA, USA in the laboratory of prof. Matthew Wilson in 2011. His research has focused on age-related memory impairment and early pathophysiological steps in Alzheimer's disease. He has used both aged rats and genetically modified mice as disease models and applied various in vivo electrophysiological recording techniques, behavioral testing and a variety of histopathological methods in his research. More recently, he has also combined morphological analysis and EEG recordings in rodents with in vivo structural and functional MRI in collaboration with Professor Olli Gröhn at A. I. Virtanen Institute. He has contributed to over 200 international peer-reviewed publications, which have been cited over 10,000 times.

Moderator of 1 Session

Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
02:45 PM - 04:45 PM
Room
ONSITE: 131-132

Presenter of 1 Presentation

PRECLINICAL ASSESSMENT OF DRUG TREATMENT OPTIONS FOR SLEEP-RELATED EPILEPTIC SPIKING IN ALZHEIMER'S DISEASE

Session Type
SYMPOSIUM
Date
Sat, 19.03.2022
Session Time
02:45 PM - 04:45 PM
Room
ONSITE: 131-132
Lecture Time
03:15 PM - 03:30 PM

Abstract

Aims

Epileptic spiking without motor manifestations can be found in 30-40% patients with early AD. This number may still be an underestimate as this spiking occurs almost exclusively during sleep and may limit to the deep temporal lobe. Further, AD patients with subclinical epileptiform
activity have about twice faster cognitive decline during a follow-up of 3-5 years (Vossel K Ann. Neurol. 2016; Horvath A EEG Clin Neurophys. 2021). Treating epileptic spiking during sleep may thus offer a way to slow down AD progression, but so far there is no published clinical study on the topic, calling for preclinical testing to guide the choice of optimal drug treatments.

Methods

Ten male APP/PS1 mice (3-5 months) were implanted with EEG screw electrodes and hippocampal triple wire electrodes to record local field potentials. Sleep was monitored by video-recording and neck EMG. We tested the standard AD-drugs donepezil and memantine as well as anti-epileptic drugs levetiracetam and lamotrigine recommended for AD patients with epilepsy. In addition, we administered the gamma-secretase inhibitor semagacestat to acutely reduce amyloid-beta levels and the anti-inflammatory tetracycline derivative minocycline to suppress neuroinflammation. The analysis focused on hippocampally generated giant spikes and cortical spike-wave dischanges and was done within-subject in reference to a repeated vehicle injection.

Results

Levetiracetam decreased while lamotrigine unexpectedly increased sleep-related giant spikes in APP/PS1 mice. Both reduced cortical spike-wave discharges, whereas memantine increased their prevalence. Other drugs had no significant effects.

Conclusions

Levetiracetam proved to be an effective treatment for sleep-related epileptic spiking while lamotrigine should be used with caution.

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