PMID- 36567653
OWN - NLM
STAT- MEDLINE
DCOM- 20230110
LR  - 20230205
IS  - 1098-2302 (Electronic)
IS  - 0012-1630 (Linking)
VI  - 65
IP  - 1
DP  - 2023 Jan
TI  - The effects of postnatal erythropoietin and nano-erythropoietin on behavioral 
      alterations by mediating K-Cl co-transporter 2 in the valproic acid-induced rat 
      model of autism.
PG  - e22353
LID - 10.1002/dev.22353 [doi]
AB  - In this study, based on the excitatory/inhibitory imbalance theory of autism, the 
      time window of GABA switch, the role of K-Cl co-transporter 2 (KCC2) in 
      adjustment GABA switch, and brain permeability to erythropoietin (EPO), the 
      effects of postnatal -EPO and- nano- erythropoietin (NEPO) have been evaluated in 
      the valproic acid (VPA) rat model of autism. The VPA was administered for animal 
      modeling of autism at gestational day (GD) 12.5 (600 mg/kg). Male offsprings were 
      injected with EPO and NEPO in a clinically proper postnatal dosing regimen on 
      postnatal days (PND) 1-5, and autistic-like behaviors were tested at the end of 
      the first month. Then animals were sacrificed, and neuron morphology and KCC2 
      expression were examined by Nissl staining and Western blot. According to our 
      findings, high-dose NEPO improved autism-associated phenotypes. Neuroprotective 
      effects of EPO and NEPO have been shown in the hippocampus. Postnatal NEPO 
      treatment reversed KCC2 expression abnormalities induced by prenatal VPA. Our 
      results might support the role of KCC2 in ASD and the excitatory/inhibitory 
      imbalance hypothesis. We suggested Nano- erythropoietin and other KCC2 
      interventions as a new approach to the early treatment and prevention of autism.
CI  - (c) 2022 Wiley Periodicals LLC.
FAU - Haratizadeh, Sara
AU  - Haratizadeh S
AD  - Student Research Committee, Kerman University of Medical Sciences, Kerman, Iran.
AD  - Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman 
      University of Medical Sciences, Kerman, Iran.
FAU - Ranjbar, Mehdi
AU  - Ranjbar M
AD  - Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University 
      of Medical Sciences, Kerman, Iran.
FAU - Darvishzadeh-Mahani, Fatemeh
AU  - Darvishzadeh-Mahani F
AD  - Neuroscience Research Center, Institute of Neuropharmacology, Kerman University 
      of Medical Sciences, Kerman, Iran.
FAU - Basiri, Mohsen
AU  - Basiri M
AD  - Neuroscience Research Center, Institute of Neuropharmacology, Kerman University 
      of Medical Sciences, Kerman, Iran.
AD  - Department of Anatomical Sciences, Afzalipour School of Medicine, Kerman 
      University of Medical Sciences, Kerman, Iran.
FAU - Nozari, Masoumeh
AU  - Nozari M
AD  - Neuroscience Research Center, Institute of Neuropharmacology, Kerman University 
      of Medical Sciences, Kerman, Iran.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Dev Psychobiol
JT  - Developmental psychobiology
JID - 0164074
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 0 (Symporters)
RN  - 614OI1Z5WI (Valproic Acid)
RN  - 11096-26-7 (Erythropoietin)
RN  - 0 (Slc12a5 protein, rat)
SB  - IM
MH  - Animals
MH  - Female
MH  - Humans
MH  - Male
MH  - Pregnancy
MH  - Rats
MH  - *Autistic Disorder/chemically induced/drug therapy/metabolism
MH  - Behavior, Animal/drug effects/physiology
MH  - Disease Models, Animal
MH  - gamma-Aminobutyric Acid/metabolism/pharmacology/therapeutic use
MH  - *Hippocampus/drug effects/metabolism
MH  - Prenatal Exposure Delayed Effects/metabolism
MH  - *Symporters/metabolism/pharmacology/therapeutic use
MH  - Valproic Acid/pharmacology
MH  - *Erythropoietin/pharmacology/therapeutic use
OTO - NOTNLM
OT  - K-Cl co-transporter 2
OT  - autism
OT  - erythropoietin
OT  - nano-erythropoietin
OT  - valproic acid
EDAT- 2022/12/27 06:00
MHDA- 2022/12/28 06:00
CRDT- 2022/12/26 03:13
PHST- 2022/09/28 00:00 [revised]
PHST- 2022/08/25 00:00 [received]
PHST- 2022/10/31 00:00 [accepted]
PHST- 2022/12/26 03:13 [entrez]
PHST- 2022/12/27 06:00 [pubmed]
PHST- 2022/12/28 06:00 [medline]
AID - 10.1002/dev.22353 [doi]
PST - ppublish
SO  - Dev Psychobiol. 2023 Jan;65(1):e22353. doi: 10.1002/dev.22353.