Lithium enhances long-term potentiation independently of hippocampal neurogenesis in the rat dentate gyrus.
We measured the temporal and spatial profiles of neural precursor cells, hippocampal long-term potentiation (LTP), and signaling molecules in neurogenesis-induced adult rats. Chronic lithium treatment produced a significant 54% and 40% increase in the numbers of bromodeoxyuridine [BrdU(+)] cells after 12 h and 28 days, respectively, after treatment completion in the dentate gyrus (DG). Both LTP obtained from slices perfused with artificial cerebrospinal fluid (ACSF-LTP) and LTP recorded in the presence of bicuculline (bicuculline-LTP) were significantly greater in the lithium group than in the saline controls. Although the number of BrdU(+) cells, approximately 90% of which were double-labeled with a neural marker neuronal nuclear protein, were markedly increased in the granule cell layer (GCL) 28 days after the completion of the 28-day lithium treatment, the magnitude of LTP observed at this time was similar to that observed 12 h after completing the 28-day lithium treatment. However, protein levels of calcium and calmodulin-dependent protein kinase II, p-Elk and TrkB were highly elevated until 28 days after the 28-day lithium treatment. Acute lithium treatment for 2 days also enhanced LTP, which was accompanied by the elevated expression of p-CREB, but not by neurogenesis. Our results suggest that the enhancement of LTP is independent of the increased number of neurons per se and it is more closely associated with key molecules, which are probably involved in neurogenesis.
Son
Hyeon
H
Department of Biochemistry, Hanyang University College of Medicine, 17 Haengdang-dong, Sungdong-gu, Seoul 133-791, South Korea. hyeonson@hanyang.ac.kr
Yu
In Tag
IT
Hwang
Se-Jin
SJ
Kim
Jin Seuk
JS
Lee
Sang-Hun
SH
Lee
Yong-Sung
YS
Kaang
Bong-Kiun
BK
Lee
Sang-Hum
SH
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001973:Bromodeoxyuridine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D018891:Dentate Gyrus / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D018756:GABA Antagonists / Q000494:pharmacology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D018756:GABA Antagonists; D008094:Lithium; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D001973:Bromodeoxyuridine; D001640:Bicuculline