New GABAergic Neurogenesis in the Hippocampal CA1 Region of a Gerbil Model of Long-Term Survival after Transient Cerebral Ischemic Injury.
We investigated the probability of newly generated neurons that could survive and mature in the ischemic hippocampal CA1 region (CA1) of a gerbil model of transient cerebral ischemia. Neuronal death was shown in the stratum pyramidale (SP) from 4 days post-ischemia, and a significant increase in NeuN-positive ((+) ) neurons was found in the SP at 180 days post-ischemia. 5-Bromo-2-deoxyuridine (BrdU)(+) cells were co-stained with NeuN and glutamic decarboxylase 67 (GAD67). Brain-derived neurotrophic factor (BDNF) immunoreactivity and protein level was shown in nonpyramidal cells from 4 days post-ischemia, and the immunoreactivity was strong at 30 days post-ischemia and not significantly changed until 180 days post-ischemia. Furthermore, TrkB immunoreactivity was co-stained with GAD67 when we examined at 180 days post-ischemia. Myelin basic protein (MBP)(+) nerve fibers were reduced at 4 days post-ischemia and maintained until 60 days post-ischemia, and MBP immunoreactivity and levels were significantly increased at 180 days post-ischemia. In the passive avoidance test, cognitive dysfunction was improved at 180 days post-ischemia. These results suggest that the differentiation of neural progenitor cells into new GABAergic neurons may be promoted via BDNF in the ischemic CA1 and that the neurogenesis may partially mediate the recovery of cognitive impairments via increasing myelinated nerve fibers.
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
Jae-Chul
JC
Lee
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
Joon Ha
JH
Park
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
Ji Hyeon
JH
Ahn
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
In Hye
IH
Kim
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
Jeong Hwi
JH
Cho
Department of Anatomy, College of Veterinary Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
Jung Hoon
JH
Choi
Department of Oral Anatomy, College of Dentistry, Gangneung-Wonju National University, Gangneung, 210-702, South Korea.
Ki-Yeon
KY
Yoo
Department of Pharmacy, College of Pharmacy, Dankook University, Cheonan, 330-714, South Korea.
Choong Hyun
CH
Lee
Department of Anatomy and Cell Biology, College of Veterinary Medicine, and Research Institute for Veterinary Science, Seoul National University, Seoul, 151-742, South Korea.
In Koo
IK
Hwang
Department of Emergency Medicine, and Institute of Medical Sciences, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
Jun Hwi
JH
Cho
Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul, 120-749, South Korea.
Young-Guen
YG
Kwon
Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
Young-Myeong
YM
Kim
Department of Food Science and Nutrition, Hallym University, Chuncheon, 200-702, South Korea.
Il Jun
IJ
Kang
Department of Neurobiology, School of Medicine, Kangwon National University, Chuncheon, 200-701, South Korea.
Moo-Ho
MH
Won
D000818:Animals; D001362:Avoidance Learning; D002545:Brain Ischemia / Q000401:mortality* / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D001973:Bromodeoxyuridine / Q000378:metabolism; D056547:CA1 Region, Hippocampal / Q000473:pathology*; D002135:Calcium-Binding Proteins; D002452:Cell Count; D004268:DNA-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D059330:GABAergic Neurons / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D005849:Gerbillinae; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005968:Glutamate Decarboxylase / Q000378:metabolism; D008297:Male; D008840:Microfilament Proteins; D004676:Myelin Basic Protein / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D011930:Reaction Time; D013997:Time Factors
C112986:AIF1 protein, human; D019208:Brain-Derived Neurotrophic Factor; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D004676:Myelin Basic Protein; D005968:Glutamate Decarboxylase; C402565:glutamate decarboxylase 1; D010751:Phosphopyruvate Hydratase; D001973:Bromodeoxyuridine
GABAergic neuron; hippocampal CA1; myelinated nerve fibers; neurogenesis; transient cerebral ischemia