PMID- 34695393
OWN - NLM
STAT- MEDLINE
DCOM- 20220322
LR  - 20220322
IS  - 1872-6240 (Electronic)
IS  - 0006-8993 (Linking)
VI  - 1773
DP  - 2021 Dec 15
TI  - Chronic stimulation of the serotonergic 5-HT4 receptor modulates 
      amyloid-beta-related impairments in synaptic plasticity and memory deficits in 
      male rats.
PG  - 147701
LID - S0006-8993(21)00558-8 [pii]
LID - 10.1016/j.brainres.2021.147701 [doi]
AB  - Alzheimer's disease (AD) is a neurodegenerative disease characterized by memory 
      decline and impaired hippocampal synaptic plasticity. The serotonin 5-HT4 
      receptor is involved in learning and memory processes. This study explored the 
      effects of chronic stimulation of 5-HT4R on cognition, memory, long-term 
      potentiation (LTP), paired-pulse ratio (PPR), and neuronal apoptosis in a rat 
      model of amyloid-beta (Abeta)-induced AD. Thirty-five male Wistar rats were randomly 
      divided into three groups as follows: the sham, Abeta, and Abeta + BIMU8 groups. Abeta 
      (6 microg/microl) was administrated by intracerebroventricular (icv) injection. The 
      animals were treated with BIMU8 (1 mug/muL, ICV) as a 5-HT4R agonist for 30 days. 
      Memory and behavioral changes were assessed by the passive avoidance learning, 
      novel object recognition, open field, and elevated plus maze tests. Hippocampal 
      synaptic plasticity was evaluated in the dentate gyrus (DG) in response to the 
      stimulation applied to the perforant pathway. Furthermore, neuronal apoptosis was 
      measured in the hippocampus. Data were analyzed by SPSS version 19 using one-way 
      ANOVA, followed by Tukey's post hoc test. Abeta induced memory deficits and neuronal 
      loss and inhibited LTP induction. Abeta also increased the normalized PPR. BIMU8 
      enhanced the slope of the field excitatory postsynaptic potential in LTP and 
      improved cognition behavior. Paired-pulse inhibition or facilitation was not 
      affected by LTP induction in Abeta animals receiving the BIMU8. It can be concluded 
      that the stimulation of the 5-HT(4) receptor modulated the Abeta-induced cognition 
      and memory deficits, probably via a decrease in the hippocampal apoptotic neurons 
      and an improvement in the hippocampal synaptic functions without involving its 
      inhibitory interneurons.
CI  - Copyright (c) 2021. Published by Elsevier B.V.
FAU - Hashemi-Firouzi, Nasrin
AU  - Hashemi-Firouzi N
AD  - Department of Physiology, School of Medicine, Hamadan University of Medical 
      Sciences, Hamadan, Iran.
FAU - Shahidi, Siamak
AU  - Shahidi S
AD  - Department of Physiology, School of Medicine, Hamadan University of Medical 
      Sciences, Hamadan, Iran. Electronic address: shahidi@umsha.ac.ir.
FAU - Soleimani Asl, Sara
AU  - Soleimani Asl S
AD  - Anatomy Department, School of Medicine, Hamadan University of Medical Sciences, 
      Hamadan, Iran.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20211022
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Benzimidazoles)
RN  - 0 (Bridged Bicyclo Compounds, Heterocyclic)
RN  - 0 (Serotonin 5-HT4 Receptor Agonists)
RN  - 134296-40-5 
      ((endo-N-8-methyl-8-azabicyclo-(3.2.1)oct-3-yl)-2,3-dihydro-3-isopropyl-2-oxo-1H-benzimidazol-1-carboxamide)
RN  - 158165-40-3 (Receptors, Serotonin, 5-HT4)
SB  - IM
MH  - Amyloid beta-Peptides/*pharmacology
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Avoidance Learning/drug effects
MH  - Behavior, Animal/drug effects
MH  - Benzimidazoles/pharmacology/therapeutic use
MH  - Bridged Bicyclo Compounds, Heterocyclic/pharmacology/therapeutic use
MH  - Dentate Gyrus/drug effects/metabolism
MH  - Excitatory Postsynaptic Potentials/drug effects
MH  - Hippocampus/*drug effects/metabolism
MH  - Male
MH  - Memory/*drug effects
MH  - Memory Disorders/*drug therapy/metabolism
MH  - Neuronal Plasticity/*drug effects
MH  - Neurons/drug effects/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Serotonin, 5-HT4/*metabolism
MH  - Serotonin 5-HT4 Receptor Agonists/*pharmacology
OTO - NOTNLM
OT  - 5-HT(4) receptor
OT  - Alzheimer disease
OT  - Hippocampus
OT  - Long-term potentiation
OT  - Rat
EDAT- 2021/10/26 06:00
MHDA- 2022/03/23 06:00
CRDT- 2021/10/25 20:10
PHST- 2021/05/20 00:00 [received]
PHST- 2021/10/14 00:00 [revised]
PHST- 2021/10/18 00:00 [accepted]
PHST- 2021/10/26 06:00 [pubmed]
PHST- 2022/03/23 06:00 [medline]
PHST- 2021/10/25 20:10 [entrez]
AID - S0006-8993(21)00558-8 [pii]
AID - 10.1016/j.brainres.2021.147701 [doi]
PST - ppublish
SO  - Brain Res. 2021 Dec 15;1773:147701. doi: 10.1016/j.brainres.2021.147701. Epub 
      2021 Oct 22.