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Current Psychopharmacology

Editor-in-Chief

ISSN (Print): 2211-5560
ISSN (Online): 2211-5579

General Research Article

The Plastic and Functional Changes in Hippocampal Neurons During Pregnancy, Delivery and Postpartum are Reversed by Offspring Deprivation

Author(s): Maria C. Mostallino*, Pietro P. Secci, Elena Paci, Maria L. Mura, Elisabetta Maciocco, Enrico Sanna and Giovanni Biggio

Volume 10, Issue 1, 2021

Published on: 18 August, 2020

Page: [73 - 83] Pages: 11

DOI: 10.2174/2211556009999200819102313

Price: $65

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Abstract

Background: Pregnancy and lactation are governed by hormones and neurophysiological processes, including differential expression of trophic factors, functional and structural synaptic plasticity, and neurogenesis in different brain areas.

Objectives: The aim of the study was to evaluate the number of neurotrophic factors, synaptic plasticity, and neurogenesis in the hippocampus of rats during pregnancy, lactation, as well as in dams that were deprived of their pups one week after birth or treated with Finasteride or Clomiphene.

Methods: Adult female Sprague Dawley CD rats were treated with finasteride (25 mg/kg, subcutaneously) or clomiphene (5 mg/kg, intragastrically) from day 12 to 18 of pregnancy. Dams during pregnancy, lactation, and those deprived of their pups, which were sacrificed 7 days after delivery, were used to study Brain-Derived Neurotrophic Factor (BDNF) and Activity-regulated Cytoskeletal (Arc) protein expression, dendritic spine density (DSD), and cell proliferation in the hippocampus.

Results: BDNF, Arc, and DSD markedly increased after 21 days of pregnancy (the time of delivery), an effect that lasted for 21 days during lactation and was abolished by physiological weaning (21 days after delivery). The modifications in the mentioned parameters were associated with a dramatic reduction of neurosteroid content when compared to estrus females. In contrast, after 21 days of pregnancy, an increase in cell proliferation and a decrease during the first three weeks of postpartum were observed. Finasteride and clomifene failed to modify the changes in BDNF and Arc content elicited by pregnancy and delivery. Pups deprivation induced a rapid reduction in the amount of BDNF, Arc, and DSD while increasing cell proliferation.

Conclusion: In rats, the changes in plastic properties of hippocampal neurons during pregnancy, lactation, and pups deprivation may play a crucial role in the modulation of maternal care.

Keywords: Clomiphene, finasteride, hippocampal plasticity, postpartum, pregnancy, stress.

Graphical Abstract

[1]
Brunton PJ, Russell JA. The expectant brain: adapting for motherhood. Nat Rev Neurosci 2008; 9(1): 11-25.
[http://dx.doi.org/10.1038/nrn2280] [PMID: 18073776]
[2]
Pawluski JL, Brummelte S, Barha CK, Crozier TM, Galea LA. Effects of steroid hormones on neurogenesis in the hippocampus of the adult female rodent during the estrous cycle, pregnancy, lactation and aging. Front Neuroendocrinol 2009; 30(3): 343-57.
[http://dx.doi.org/10.1016/j.yfrne.2009.03.007] [PMID: 19361542]
[3]
Pawluski JL, Lambert KG, Kinsley CH. Neuroplasticity in the maternal hippocampus: Relation to cognition and effects of repeated stress. Horm Behav 2016; 77: 86-97.
[http://dx.doi.org/10.1016/j.yhbeh.2015.06.004] [PMID: 26122302]
[4]
Hillerer KM, Jacobs VR, Fischer T, Aigner L. The maternal brain: an organ with peripartal plasticity. Neural Plast 2014; 2014574159
[http://dx.doi.org/10.1155/2014/574159] [PMID: 24883213]
[5]
Rasia-Filho AA, Fabian C, Rigoti KM, Achaval M. Influence of sex, estrous cycle and motherhood on dendritic spine density in the rat medial amygdala revealed by the Golgi method. Neuroscience 2004; 126(4): 839-47.
[http://dx.doi.org/10.1016/j.neuroscience.2004.04.009 PMID: 15207319]
[6]
Holschbach MA, Lonstein JS. Motherhood and infant contact regulate neuroplasticity in the serotonergic midbrain dorsal raphe. Psychoneuroendocrinology 2017; 76: 97-106.
[http://dx.doi.org/10.1016/j.psyneuen.2016.10.023] [PMID: 27898359]
[7]
Kinsley CH, Trainer R, Stafisso-Sandoz G, et al. Motherhood and the hormones of pregnancy modify concentrations of hippocampal neuronal dendritic spines. Horm Behav 2006; 49(2): 131-42.
[http://dx.doi.org/10.1016/j.yhbeh.2005.05.017] [PMID: 16005000]
[8]
Akbari EM, Chatterjee D, Lévy F, Fleming AS. Experience-dependent cell survival in the maternal rat brain. Behav Neurosci 2007; 121(5): 1001-11.
[http://dx.doi.org/10.1037/0735-7044.121.5.1001] [PMID: 17907831]
[9]
Brusco J, Wittmann R, de Azevedo MS, et al. Plasma hormonal profiles and dendritic spine density and morphology in the hippocampal CA1 stratum radiatum, evidenced by light microscopy, of virgin and postpartum female rats. Neurosci Lett 2008; 438(3): 346-50.
[http://dx.doi.org/10.1016/j.neulet.2008.04.063] [PMID: 18486341]
[10]
Hoekzema E, Barba-Müller E, Pozzobon C, et al. Pregnancy leads to long-lasting changes in human brain structure. Nat Neurosci 2017; 20(2): 287-96.
[http://dx.doi.org/10.1038/nn.4458] [PMID: 27991897]
[11]
Barba-Müller E, Craddock S, Carmona S, Hoekzema E. Brain plasticity in pregnancy and the postpartum period: links to maternal caregiving and mental health. Arch Women Ment Health 2019; 22(2): 289-99.
[http://dx.doi.org/10.1007/s00737-018-0889-z] [PMID: 30008085]
[12]
Wan L, Tu T, Zhang QL, Jiang J, Yan XX. Pregnancy promotes maternal hippocampal neurogenesis in guinea pigs. Neural Plast 2019; 20195765284
[http://dx.doi.org/10.1155/2019/5765284] [PMID: 31097956]
[13]
Hoekzema E, Tamnes CK, Berns P, et al. Becoming a mother entails anatomical changes in the ventral striatum of the human brain that facilitate its responsiveness to offspring cues. Psychoneuroendocrinology 2020; 112104507
[http://dx.doi.org/10.1016/j.psyneuen.2019.104507 PMID: 31757430]
[14]
Leal G, Afonso PM, Salazar IL, Duarte CB. Regulation of hippocampal synaptic plasticity by BDNF. Brain Res 2015; 1621: 82-101.
[http://dx.doi.org/10.1016/j.brainres.2014.10.019] [PMID: 25451089]
[15]
Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci 2006; 7(9): 697-709.
[http://dx.doi.org/10.1038/nrn1970] [PMID: 16924259]
[16]
Yasuhara T, Hara K, Maki M, et al. Lack of exercise, via hindlimb suspension, impedes endogenous neurogenesis. Neuroscience 2007; 149(1): 182-91.
[http://dx.doi.org/10.1016/j.neuroscience.2007.07.045 PMID: 17869433]
[17]
Branchi I. The mouse communal nest: investigating the epigenetic influences of the early social environment on brain and behavior development. Neurosci Biobehav Rev 2009; 33(4): 551-9.
[http://dx.doi.org/10.1016/j.neubiorev.2008.03.011 PMID: 18471879]
[18]
Boger HA, Mannangatti P, Samuvel DJ, et al. Effects of brain-derived neurotrophic factor on dopaminergic function and motor behavior during aging. Genes Brain Behav 2011; 10(2): 186-98.
[http://dx.doi.org/10.1111/j.1601-183X.2010.00654.x PMID: 20860702]
[19]
Fredriksson A, Stigsdotter IM, Hurtig A, Ewalds-Kvist B, Archer T. Running wheel activity restores MPTP-induced functional deficits. J Neural Transm (Vienna) 2011; 118(3): 407-20.
[http://dx.doi.org/10.1007/s00702-010-0474-8] [PMID: 20852902]
[20]
Rolls A, Schori H, London A, Schwartz M. Decrease in hippocampal neurogenesis during pregnancy: a link to immunity. Mol Psychiatry 2008; 13(5): 468-9.
[http://dx.doi.org/10.1038/sj.mp.4002126] [PMID: 18421294]
[21]
Kim SK, Hwang IK, Yoo KY, et al. Pregnancy inhibits cell proliferation and neuroblast differentiation without neuronal damage in the hippocampal dentate gyrus in C57BL/6N mice. Brain Res 2010; 1315: 25-32.
[http://dx.doi.org/10.1016/j.brainres.2009.12.029] [PMID: 20026318]
[22]
Pawluski JL, Barakauskas VE, Galea LA. Pregnancy decreases oestrogen receptor alpha expression and pyknosis, but not cell proliferation or survival, in the hippocampus. J Neuroendocrinol 2010; 22(4): 248-57.
[http://dx.doi.org/10.1111/j.1365-2826.2010.01960.x PMID: 20136685]
[23]
Pawluski JL, van den Hove DL, Rayen I, Prickaerts J, Steinbusch HW. Stress and the pregnant female: Impact on hippocampal cell proliferation, but not affective-like behaviors. Horm Behav 2011; 59(4): 572-80.
[http://dx.doi.org/10.1016/j.yhbeh.2011.02.012] [PMID: 21376727]
[24]
Hillerer KM, Neumann ID, Couillard-Despres S, Aigner L, Slattery DA. Lactation-induced reduction in hippocampal neurogenesis is reversed by repeated stress exposure. Hippocampus 2014; 24(6): 673-83.
[http://dx.doi.org/10.1002/hipo.22258] [PMID: 24615851]
[25]
Strasser A, Skalicky M, Hansalik M, Viidik A. The impact of environment in comparison with moderate physical exercise and dietary restriction on BDNF in the cerebral parietotemporal cortex of aged Sprague-Dawley rats. Gerontology 2006; 52(6): 377-81.
[http://dx.doi.org/10.1159/000095117] [PMID: 16921250]
[26]
Baroncelli L, Braschi C, Spolidoro M, Begenisic T, Sale A, Maffei L. Nurturing brain plasticity: impact of environmental enrichment. Cell Death Differ 2010; 17(7): 1092-103.
[http://dx.doi.org/10.1038/cdd.2009.193] [PMID: 20019745]
[27]
Cowansage KK, LeDoux JE, Monfils MH. Brain-derived neurotrophic factor: a dynamic gatekeeper of neural plasticity. Curr Mol Pharmacol 2010; 3(1): 12-29.
[http://dx.doi.org/10.2174/1874467211003010012] [PMID: 20030625]
[28]
Concas A, Mostallino MC, Porcu P, et al. Role of brain allopregnanolone in the plasticity of gamma-aminobutyric acid type a receptor in rat brain during pregnancy and after delivery. Proc Natl Acad Sci USA 1998; 95(22): 13284-9.
[http://dx.doi.org/10.1073/pnas.95.22.13284] [PMID: 9789080]
[29]
Trapani G, Dazzi L, Pisu MG, Reho A, Seu E, Biggio G. A rapid method for obtaining finasteride, a 5alpha-reductase inhibitor, from commercial tablets. Brain Res Brain Res Protoc 2002; 9(2): 130-4.
[http://dx.doi.org/10.1016/S1385-299X(02)00146-0 PMID: 12034332]
[30]
Pisu MG, Dore R, Mostallino MC, et al. Down-regulation of hippocampal BDNF and Arc associated with improvement in aversive spatial memory performance in socially isolated rats. Behav Brain Res 2011; 222(1): 73-80.
[http://dx.doi.org/10.1016/j.bbr.2011.03.021] [PMID: 21420441]
[31]
Talani G, Licheri V, Biggio F, et al. Enhanced glutamatergic synaptic plasticity in the hippocampal ca1 field of food-restricted rats: involvement of CB1 Receptors. Neuropsychopharmacology 2016; 41(5): 1308-18.
[http://dx.doi.org/10.1038/npp.2015.280] [PMID: 26354043]
[32]
Tanapat P, Hastings NB, Reeves AJ, Gould E. Estrogen stimulates a transient increase in the number of new neurons in the dentate gyrus of the adult female rat. J Neurosci 1999; 19(14): 5792-801.
[http://dx.doi.org/10.1523/JNEUROSCI.19-14-05792.1999] [PMID: 10407020]
[33]
Gundersen HJ, Jensen EB. The efficiency of systematic sampling in stereology and its prediction. J Microsc 1987; 147(Pt 3): 229-63.
[http://dx.doi.org/10.1111/j.1365-2818.1987.tb02837.x] [PMID: 3430576]
[34]
Woolley CS, Gould E, McEwen BS. Exposure to excess glucocorticoids alters dendritic morphology of adult hippocampal pyramidal neurons. Brain Res 1990; 531(1-2): 225-231. a.
[http://dx.doi.org/10.1016/0006-8993(90)90778-A] [PMID: 1705153]
[35]
Woolley CS, Gould E, Frankfurt M, McEwen BS. Naturally occurring fluctuation in dendritic spine density on adult hippocampal pyramidal neurons. J Neurosci 1990; 10(12): 4035-4039. b.
[http://dx.doi.org/10.1523/JNEUROSCI.10-12-04035.1990] [PMID: 2269895]
[36]
Woolley CS, McEwen BS. Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci 1992; 12(7): 2549-54.
[http://dx.doi.org/10.1523/JNEUROSCI.12-07-02549.1992] [PMID: 1613547]
[37]
Woolley CS, McEwen BS. Roles of estradiol and progesterone in regulation of hippocampal dendritic spine density during the estrous cycle in the rat. J Comp Neurol 1993; 336(2): 293-306.
[http://dx.doi.org/10.1002/cne.903360210] [PMID: 8245220]
[38]
Alvarez-Salvado E, Pallarés V, Moreno A, Canals S. Functional MRI of long-term potentiation: imaging network plasticity. Philos Trans R Soc Lond B Biol Sci 2013; 369(1633)20130152
[http://dx.doi.org/10.1098/rstb.2013.0152] [PMID: 24298154]
[39]
Blom H, Brismar H. STED microscopy: increased resolution for medical research? J Intern Med 2014; 276(6): 560-78.
[http://dx.doi.org/10.1111/joim.12278] [PMID: 24980774]
[40]
Chéreau R, Tønnesen J, Nägerl UV. STED microscopy for nanoscale imaging in living brain slices. Methods 2015; 88: 57-66.
[http://dx.doi.org/10.1016/j.ymeth.2015.06.006] [PMID: 26070997]
[41]
Sadakane O, Masamizu Y, Watakabe A, et al. Long-term two-photon calcium imaging of neuronal populations with subcellular resolution in adult non-human primates. Cell Rep 2015; 13(9): 1989-99.
[http://dx.doi.org/10.1016/j.celrep.2015.10.050] [PMID: 26655910]
[42]
Bramham CR. Local protein synthesis, actin dynamics, and LTP consolidation. Curr Opin Neurobiol 2008; 18(5): 524-31.
[http://dx.doi.org/10.1016/j.conb.2008.09.013] [PMID: 18834940]
[43]
Bennett MR, Lagopoulos J. Stress and trauma: BDNF control of dendritic-spine formation and regression. Prog Neurobiol 2014; 112: 80-99.
[http://dx.doi.org/10.1016/j.pneurobio.2013.10.005 PMID: 24211850]
[44]
Karpova NN. Role of BDNF epigenetics in activity-dependent neuronal plasticity. Neuropharmacology 2014; 76(Pt C): 709-18.
[http://dx.doi.org/10.1016/j.neuropharm.2013.04.002 PMID: 23587647]
[45]
Korb E, Finkbeiner S. Arc in synaptic plasticity: from gene to behavior. Trends Neurosci 2011; 34(11): 591-8.
[http://dx.doi.org/10.1016/j.tins.2011.08.007] [PMID: 21963089]
[46]
Banasr M, Hery M, Brezun JM, Daszuta A. Serotonin mediates oestrogen stimulation of cell proliferation in the adult dentate gyrus. Eur J Neurosci 2001; 14(9): 1417-24.
[http://dx.doi.org/10.1046/j.0953-816x.2001.01763.x PMID: 11722603]
[47]
Darnaudéry M, Perez-Martin M, Del Favero F, Gomez-Roldan C, Garcia-Segura LM, Maccari S. Early motherhood in rats is associated with a modification of hippocampal function. Psychoneuroendocrinology 2007; 32(7): 803-12.
[http://dx.doi.org/10.1016/j.psyneuen.2007.05.012] [PMID: 17640823]
[48]
Leuner B, Mirescu C, Noiman L, Gould E. Maternal experience inhibits the production of immature neurons in the hippocampus during the postpartum period through elevations in adrenal steroids. Hippocampus 2007; 17(6): 434-42.
[http://dx.doi.org/10.1002/hipo.20278] [PMID: 17397044]
[49]
Pawluski JL, Galea LA. Reproductive experience alters hippocampal neurogenesis during the postpartum period in the dam. Neuroscience 2007; 149(1): 53-67.
[http://dx.doi.org/10.1016/j.neuroscience.2007.07.031 PMID: 17869008]
[50]
Voogt JL, Sar M, Meites J. Influence of cycling, pregnancy, labor, and suckling on corticosterone-ACTH levels. Am J Physiol 1969; 216(3): 655-8.
[http://dx.doi.org/10.1152/ajplegacy.1969.216.3.655 PMID: 4303907]
[51]
Stern JM, Goldman L, Levine S. Pituitary-adrenal responsiveness during lactation in rats. Neuroendocrinology 1973; 12(3): 179-91.
[http://dx.doi.org/10.1159/000122167] [PMID: 4353345]
[52]
Walker CD, Lightman SL, Steele MK, Dallman MF. Suckling is a persistent stimulus to the adrenocortical system of the rat. Endocrinology 1992; 130(1): 115-25.
[http://dx.doi.org/10.1210/endo.130.1.1309321] [PMID: 1309321]
[53]
Fischer D, Patchev VK, Hellbach S, Hassan AH, Almeida OF. Lactation as a model for naturally reversible hypercorticalism plasticity in the mechanisms governing hypothalamo-pituitary-adrenocortical activity in rats. J Clin Invest 1995; 96(3): 1208-15.
[http://dx.doi.org/10.1172/JCI118153] [PMID: 7657793]
[54]
Tanapat P, Hastings NB, Rydel TA, Galea LA, Gould E. Exposure to fox odor inhibits cell proliferation in the hippocampus of adult rats via an adrenal hormone-dependent mechanism. J Comp Neurol 2001; 437(4): 496-504.
[http://dx.doi.org/10.1002/cne.1297] [PMID: 11503148]
[55]
Hill MN, Kambo JS, Sun JC, Gorzalka BB, Galea LA. Endocannabinoids modulate stress-induced suppression of hippocampal cell proliferation and activation of defensive behaviours. Eur J Neurosci 2006; 24(7): 1845-9.
[http://dx.doi.org/10.1111/j.1460-9568.2006.05061.x PMID: 17067290]
[56]
Mirescu C, Gould E. Stress and adult neurogenesis. Hippocampus 2006; 16(3): 233-8.
[http://dx.doi.org/10.1002/hipo.20155] [PMID: 16411244]
[57]
Mitra R, Sundlass K, Parker KJ, Schatzberg AF, Lyons DM. Social stress-related behavior affects hippocampal cell proliferation in mice. Physiol Behav 2006; 89(2): 123-7.
[http://dx.doi.org/10.1016/j.physbeh.2006.05.047] [PMID: 16837015]
[58]
Cameron HA, McKay RD. Restoring production of hippocampal neurons in old age. Nat Neurosci 1999; 2(10): 894-7.
[http://dx.doi.org/10.1038/13197] [PMID: 10491610]

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