Abstract Objective To investigate the neuroprotective effect of leptin by observing its effect on spatial memory of rats with white matter damage in developing brain. Methods A total of 80 neonatal rats were randomly divided into 3 groups:sham-operation (n=27), model (n=27) and leptin intervention (n=27). The rats in the model and leptin intervention groups were used to prepare a model of white matter damage in developing brain, and the rats in the leptin intervention group were given leptin (100 μg/kg) diluted with normal saline immediately after modelling for 4 consecutive days. The survival rate of the rats was observed and the change in body weight was monitored. When the rats reached the age of 21 days, the Morris water maze test was used to evaluate spatial memory. Results There was no significant difference in the survival rate of rats between the three groups (P > 0.05). Within 10 days after birth, the leptin intervention group had similar body weight as the sham-operation group and significantly lower body weight than the model group (P < 0.05); more than 10 days after birth, the leptin intervention group had rapid growth with higher body weight than the model and sham-operation groups (P > 0.05). The results of place navigation showed that from the second day of experiment, there was a significant difference in the latency period between the three groups (P < 0.05); from the fourth day of experiment, the leptin intervention group had a similar latency period as the sham-operation and a significantly shorter latency period than the model group (P < 0.05). The results of space search experiment showed that compared with the sham-operation group, the model group had a significant reduction in the number of platform crossings and a significantly longer latency period (P < 0.05); compared with the model group, the leptin intervention group had a significantly increased number of platform crossings and a significantly shortened latency period (P < 0.05), while there was no significant difference between the leptin intervention and sham-operation groups. Conclusions Leptin can alleviate spatial memory impairment of rats with white matter damage in developing brain. It thus exerts a neuroprotective effect, and is worthy of further research.
FENG Er-Cui,JIANG Li. Effect of leptin on long-term spatial memory of rats with white matter damage in developing brain[J]. CJCP, 2017, 19(12): 1267-1271.
FENG Er-Cui,JIANG Li. Effect of leptin on long-term spatial memory of rats with white matter damage in developing brain[J]. CJCP, 2017, 19(12): 1267-1271.
World Health Organization. Preterm birth Fact sheet no 363. WHO[EB/OL]. (2017-11).
[2]
Burns YR, Danks M, O'Callaghan MJ, et al. Motor coordination difficulties and physical fitness of extremely-low-birthweight children[J]. Dev Med Child Neurol, 2009, 51(2):136-142.
[3]
Woodward LJ, Edgin JO, Thompson D, et al. Object working memory deficits predicted by early brain injury and development in the preterm infant[J]. Brain, 2005, 128(Pt 11):2578-2587.
[4]
Back SA, Han BH, Luo NL, et al. Selective vulnerability of late oligodendrocyte progenitors to hypoxia-ischemia[J]. J Neurosci, 2002, 22(2):455-463.
[5]
Volpe JJ. Brain injury in premature infants:a complex amalgam of destructive and developmental disturbances[J]. Lancet Neurol, 2009, 8(1):110-124.
[6]
du Plessis AJ. Neurology of the newborn infant. Preface[J]. Clin Perinatol, 2009, 36(4):xi-xiii.
[7]
Oomura Y, Hori N, Shiraishi T, et al. Leptin facilitates learning and memory performance and enhances hippocampal CA1 long-term potentiation and CaMK Ⅱ phosphorylation in rats[J]. Peptides, 2006, 27(11):2738-2749.
Favaro A, Santonastaso P, Manara R, et al. Disruption of visuospatial and somatosensory functional connectivity in anorexia nervosa[J]. Biol Psychiatry, 2012, 72(10):864-870.
[10]
Koyama KI, Asakawa A, Nakahara T, et al. Intelligence quotient and cognitive functions in severe restricting-type anorexia nervosa before and after weight gain[J]. Nutrition, 2012, 28(11-12):1132-1136.
[11]
Sternheim L, Startup H, Pretorius N, et al. An experimental exploration of social problem solving and its associated processes in anorexia nervosa[J]. Psychiatry Res, 2012, 200(2-3):524-529.
[12]
Johnston JM, Hu WT, Fardo DW, et al. Low plasma leptin in cognitively impaired ADNI subjects:gender differences and diagnostic and therapeutic potential[J]. Curr Alzheimer Res, 2014, 11(2):165-174.
[13]
Guimond D, Diabira D, Porcher C, et al. Leptin potentiates GABAergic synaptic transmission in the developing rodent hippocampus[J]. Front Cell Neurosci, 2014, 8:235.
[14]
Durakoglugil M, Irving AJ, Harvey J. Leptin induces a novel form of NMDA receptor-dependent long-term depression[J]. J Neurochem, 2005, 95(2):396-405.
[15]
Shanley LJ, Irving AJ, Harvey J. Leptin enhances NMDA receptor function and modulates hippocampal synaptic plasticity[J]. J Neurosci, 2001, 21(24):RC186.
[16]
Shanley LJ, Irving AJ, Rae MG, et al. Leptin inhibits rat hippocampal neurons via activation of large conductance calcium-activated K+ channels[J]. Nat Neurosci, 2002, 5(4):299-300.
[17]
O'Malley D, Irving AJ, Harvey J. Leptin-induced dynamic alterations in the actin cytoskeleton mediate the activation and synaptic clustering of BK channels[J]. FASEB J, 2005, 19(13):1917-1919.
[18]
Walker CD, Long H, Williams S, et al. Long-lasting effects of elevated neonatal leptin on rat hippocampal function, synaptic proteins and NMDA receptor subunits[J]. J Neurosci Res, 2007, 85(4):816-828.
[19]
Irving AJ, Wallace L, Durakoglugil D, et al. Leptin enhances NR2B-mediated N-methyl-D-aspartate responses via a mitogen-activated protein kinase-dependent process in cerebellar granule cells[J]. Neuroscience, 2006, 138(4):1137-1148.
[20]
Nagasaki H, Ohta T. Extra-uterine growth and adipocytokines in appropriate-for-gestational-age preterm infants[J]. Pediatr Int, 2015, 58(7):584-588.
[21]
Veselá PK, Kaniok R, Bayer M. Markers of bone metabolism, serum leptin levels and bone mineral density in preterm babies[J]. J Pediatr Endocrinol Metab, 2016, 29(1):27-32.
[22]
Okuma C, Hernández MI, Rodríguez P, et al. Microstructural brain and multivoxel spectroscopy in very low birth weight infants related to insulin-like growth factor concentration and early growth[J]. Horm Res Paediatr, 2013, 79(4):197-207.
[23]
Mela V, Díaz F, Borcel E, et al. Long term hippocampal and cortical changes induced by maternal deprivation and neonatal leptin treatment in male and female rats[J]. PLoS One, 2015, 10(9):e0137283.
