PMID- 33915239
OWN - NLM
STAT- MEDLINE
DCOM- 20220127
LR  - 20220127
IS  - 1872-7549 (Electronic)
IS  - 0166-4328 (Linking)
VI  - 409
DP  - 2021 Jul 9
TI  - Hyperhomocysteinemia increases susceptibility to cortical spreading depression 
      associated with photophobia, mechanical allodynia, and anxiety in rats.
PG  - 113324
LID - S0166-4328(21)00212-6 [pii]
LID - 10.1016/j.bbr.2021.113324 [doi]
AB  - Epidemiological data suggest that elevated homocysteine is associated with 
      migraine with aura. However, how homocysteine contributes to migraine is still 
      unclear. Here, we tested whether hyperhomocysteinemia (hHCY) promotes cortical 
      spreading depression (CSD), a phenomenon underlying migraine with aura, and 
      whether hHCY contributes to pain behavior. hHCY was induced by dietary methionine 
      in female rats while the testing was performed on their 6-8week-old offspring. 
      CSD and multiple unit activity (MUA) induced by KCl were recorded from the 
      primary somatosensory cortex, S1, using multichannel electrodes. In hHCY rats, 
      compared to control, we found: i) higher probability of CSD occurrence; ii) 
      induction of CSD by lower concentrations of KCl; iii) faster horizontal 
      propagation of CSD; iv) smaller CSD with longer duration; v) higher frequency of 
      MUA at CSD onset along with slower reappearance. Rats with hHCY demonstrated high 
      level of locomotor activity and grooming while spent less time in the central 
      area of the open field, indicating anxiety. These animals showed light 
      sensitivity and facial mechanical allodinia. Thus, hHCY acquired at birth 
      promotes multiple features of migraine such as higher cortical excitability, 
      mechanical allodynia, photophobia, and anxiety. Our results provide the first 
      experimental explanation for the higher occurrence of migraine with aura in 
      patients with hHCY.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Gerasimova, Elena
AU  - Gerasimova E
AD  - Department of Human and Animal Physiology, Institute of Fundamental Medicine and 
      Biology, Kazan Federal University, Kazan, Russia.
FAU - Burkhanova, Gulshat
AU  - Burkhanova G
AD  - Laboratory of Neurobiology, Institute of Fundamental Medicine and Biology, Kazan 
      Federal University, Kazan, Russia.
FAU - Chernova, Kseniya
AU  - Chernova K
AD  - Laboratory of Neurobiology, Institute of Fundamental Medicine and Biology, Kazan 
      Federal University, Kazan, Russia.
FAU - Zakharov, Andrey
AU  - Zakharov A
AD  - Laboratory of Neurobiology, Institute of Fundamental Medicine and Biology, Kazan 
      Federal University, Kazan, Russia; Department of Physiology, Kazan State Medical 
      University, Kazan, Russia.
FAU - Enikeev, Daniel
AU  - Enikeev D
AD  - Department of Human and Animal Physiology, Institute of Fundamental Medicine and 
      Biology, Kazan Federal University, Kazan, Russia.
FAU - Khaertdinov, Nail
AU  - Khaertdinov N
AD  - Department of Human and Animal Physiology, Institute of Fundamental Medicine and 
      Biology, Kazan Federal University, Kazan, Russia.
FAU - Giniatullin, Rashid
AU  - Giniatullin R
AD  - Laboratory of Neurobiology, Institute of Fundamental Medicine and Biology, Kazan 
      Federal University, Kazan, Russia; A.I.Virtanen Institute, University of Eastern, 
      Finland, Kuopio, Finland.
FAU - Sitdikova, Guzel
AU  - Sitdikova G
AD  - Department of Human and Animal Physiology, Institute of Fundamental Medicine and 
      Biology, Kazan Federal University, Kazan, Russia. Electronic address: 
      sitdikovaguzel@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210426
PL  - Netherlands
TA  - Behav Brain Res
JT  - Behavioural brain research
JID - 8004872
RN  - AE28F7PNPL (Methionine)
SB  - IM
MH  - Animals
MH  - Anxiety/etiology/*physiopathology
MH  - Behavior, Animal/*physiology
MH  - Cortical Excitability/*physiology
MH  - Cortical Spreading Depression/drug effects/*physiology
MH  - Disease Models, Animal
MH  - Female
MH  - Hyperalgesia/etiology/*physiopathology
MH  - Hyperhomocysteinemia/chemically induced/*complications
MH  - Male
MH  - Methionine/pharmacology
MH  - Migraine with Aura/etiology
MH  - Photophobia/etiology/*physiopathology
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/chemically induced
MH  - Rats
MH  - Rats, Wistar
MH  - Somatosensory Cortex/*physiopathology
OTO - NOTNLM
OT  - Allodynia
OT  - Anxiety
OT  - Cortical excitability
OT  - Cortical spreading depression
OT  - Hyperhomocysteinemia
OT  - Migraine
EDAT- 2021/04/30 06:00
MHDA- 2022/01/28 06:00
CRDT- 2021/04/29 20:14
PHST- 2020/11/18 00:00 [received]
PHST- 2021/04/23 00:00 [revised]
PHST- 2021/04/23 00:00 [accepted]
PHST- 2021/04/30 06:00 [pubmed]
PHST- 2022/01/28 06:00 [medline]
PHST- 2021/04/29 20:14 [entrez]
AID - S0166-4328(21)00212-6 [pii]
AID - 10.1016/j.bbr.2021.113324 [doi]
PST - ppublish
SO  - Behav Brain Res. 2021 Jul 9;409:113324. doi: 10.1016/j.bbr.2021.113324. Epub 2021 
      Apr 26.