Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents
Section snippets
Animals
Male db/db mice (C57BL/KsJ-db/db Jc1) and Zucker fatty rats (fa/fa) (all 7 weeks old) and their respective controls (C57BL/KsJ-db/+m Jc1 and +/+) were fed commercial food pellets (Clea Japan, Japan) and allowed free access to tap water. They were maintained in a colony room with an ambient temperature of 24±1°C and a 07.00/19.00 h light/dark photocycle. All procedures were approved by the Animal Care and Use Committee of Kyushu University and conformed to the guidelines for the use of
LTP, LTD and post-synaptic responses of CA1 neurons in Zucker rats
Fig. 1 illustrates the results obtained in Zucker fatty rats: it shows the evoked pEPSPs before and after tetanic stimulation in normal Krebs–Ringer solution and in a solution containing 10−12 M leptin. A brief PTP was seen in each solution, but LTP did not appear with or without leptin. However, as shown in Fig. 2, in control Zucker lean rats, this concentration of leptin enhanced the LTP maintenance by approximately twice (compared with that seen in normal Krebs–Ringer solution), while 10−10
Discussion
The present study demonstrated that Zucker fatty rats and db/db mice, both of which are deficient in OB-Rs, showed impairments of LTP and LTD in the CA1 hippocampal region. Although leptin enhanced LTP maintenance at 10−12 M and inhibited it at 10−10 M in lean control rats, Zucker fatty rats and db/db mice were both insensitive to leptin.
In the Morris water-maze test, Zucker rats and db/db mice each swam further than their controls before they found and climbed onto the platform under
Conclusion
In the present study, we demonstrated that Zucker fatty rats and db/db mice both showed impairments in LTP and LTD in hippocampal CA1 neurons, as well as deficits in spatial memory. This may be, at least in part, secondary to the deficiency of OB-Rs in these two animal trains. On the basis of these results, we propose that in addition to its previously reported roles, leptin may have an important role to play in the regulation of hippocampal functions and in the control of learning and memory
Acknowledgements
We thank Dr. R. Timms for a critical reading of the manuscript. This work was supported by Grants-in-Aid for Scientific Research 10470011 (to S.A.) and 11877014 (to S.A.) from the Ministry of Education, Science, and Culture of Japan.
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2022, Biomedicine and PharmacotherapyCitation Excerpt :Likewise, leptin, has also an important role in neuronal development and the cognitive process. In this regard, Li and colleagues demonstrated that leptin receptors deficient rodents (Zucker fatty rats and db / db mice) exhibited alterations in the process of LTP and long-term depression (LTD) in the hippocampal CA1 region, which affected memory and learning [73]. These results were the first to suggest a key role for leptin receptors in the cognitive process, especially those in the hippocampus and the cerebral cortex.