The Plastic and Functional Changes in Hippocampal Neurons during Preg nancy, Delivery and Postpartum Are Reversed by Offspring Deprivation

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 amount of neurotrophic factors, synaptic plasticity and neurogenesis in the hippocampus of rats during pregnancy, lactation as well as in dams that were deprived from their pups one week af-ter 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 from their pups which were sacrified 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 hip-pocampus. 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 fe-males. In contrast, after 21 days of pregnancy we observed an increase in cell proliferation and a decrease during the first three weeks of postpartum. 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 increas-ing cell proliferation. Conclusion: In rats, the changes in plastic properties of hippocampal neurons during pregnancy, lactation and pups depri-vation may play a crucial role in the modulation of maternal care.

Download Full-text

Rapid Effects of Estradiol on Dendritic Spines and Synaptic Plasticity in the Male and Female Hippocampus

Estrogens and Memory ◽

10.1093/oso/9780190645908.003.0004 ◽

2020 ◽

pp. 38-47

Author(s):

Asami Kato ◽

Gen Murakami ◽

Yasushi Hojo ◽

Sigeo Horie ◽

Suguru Kawato

Keyword(s):

Synaptic Plasticity ◽

Dendritic Spine ◽

Hippocampal Neurons ◽

Molecular Mechanisms ◽

Hippocampal Slices ◽

Spine Density ◽

Male And Female ◽

Dendritic Spine Density ◽

Male And Female Rats ◽

Rapid Modulation

Although the potent estrogen, 17β‎-estradiol (E2), has long been known to regulate the hippocampal dendritic spine density and synaptic plasticity, the molecular mechanisms through which it does so are less well understood. This chapter discusses the rapid modulation of hippocampal dendritic spine density and synaptic plasticity in male and female rats, with particular attention to studies in hippocampal slices from male rats. Among the mechanisms described are the roles of specific cell-signaling kinases and estrogen receptors in mediating the effects of E2 and progesterone on hippocampal neurons. In addition, dynamic changes of spine structures over time and sex differences in spine regulation are also considered. Finally, the chapter ends by discussing the importance of local hippocampal synthesis of E2 and androgens to hippocampal spine morphology and plasticity.

Download Full-text

Memory Impairment Induced by Borna Disease Virus 1 Infection is Associated with Reduced H3K9 Acetylation

Cellular Physiology and Biochemistry ◽

10.1159/000492890 ◽

2018 ◽

Vol 49 (1) ◽

pp. 381-394 ◽

Cited By ~ 7

Author(s):

Jie Jie ◽

Xiaoyan Xu ◽

Jinjun Xia ◽

Zhe Tu ◽

Yujie Guo ◽

...

Keyword(s):

Synaptic Plasticity ◽

Histone Acetylation ◽

Disease Virus ◽

Hippocampal Neurons ◽

Memory Impairment ◽

Sprague Dawley ◽

Borna Disease Virus ◽

Sprague Dawley Rats ◽

H3k9 Acetylation ◽

Borna Disease

Background/Aims: Borna disease virus 1 (BoDV-1) infection induces cognitive impairment in rodents. Emerging evidence has demonstrated that Chromatin remodeling through histone acetylation can regulate cognitive function. In the present study, we investigated the epigenetic regulation of chromatin that underlies BoDV-1-induced cognitive changes in the hippocampus. Methods: Immunofluorescence assay was applied to detect BoDV-1 infection in hippocampal neurons and Sprague-Dawley rats models. The histone acetylation levels both in vivo and vitro were assessed by western blots. The acetylation-regulated genes were identified by ChIP-seq and verified by RT-qPCR. Cognitive functions were evaluated with Morris Water Maze test. In addition, Golgi staining, and electrophysiology were used to study changes in synaptic structure and function. Results: BoDV-1 infection of hippocampal neurons significantly decreased H3K9 histone acetylation level and inhibited transcription of several synaptic genes, including postsynaptic density 95 (PSD95) and brain-derived neurotrophic factor (BDNF). Furthermore, BoDV-1 infection of Sprague Dawley rats disrupted synaptic plasticity and caused spatial memory impairment. These rats also exhibited dysregulated hippocampal H3K9 acetylation and decreased PSD95 and BDNF protein expression. Treatment with the HDAC inhibitor, suberanilohydroxamic acid (SAHA), attenuated the negative effects of BoDV-1. Conclusion: Our results demonstrate that regulation of H3K9 histone acetylation may play an important role in BoDV-1-induced memory impairment, whereas SAHA may confer protection against BoDV-1-induced cognitive impairments. This study finds important mechanism of BoDV-1 infection disturbing neuronal synaptic plasticity and inducing cognitive dysfunction from the perspective of histone modification.

Download Full-text

NRF2 Activation Ameliorates Oxidative Stress and Improves Mitochondrial Function and Synaptic Plasticity, and in A53T α-Synuclein Hippocampal Neurons

Antioxidants ◽

10.3390/antiox11010026 ◽

2021 ◽

Vol 11 (1) ◽

pp. 26

Author(s):

Mikah S. Brandes ◽

Jonathan A. Zweig ◽

Anita Tang ◽

Nora E. Gray

Keyword(s):

Oxidative Stress ◽

Synaptic Plasticity ◽

Mitochondrial Function ◽

Hippocampal Neurons ◽

Neuronal Loss ◽

Dimethyl Fumarate ◽

Dendritic Arborization ◽

Therapeutic Interventions ◽

Spine Density ◽

Nrf2 Activator

In Parkinson’s disease (PD), brain oxidative stress and mitochondrial dysfunction contribute to neuronal loss as well as motor and cognitive deficits. The transcription factor NRF2 has emerged as a promising therapeutic target in PD because it sits at the intersection of antioxidant and mitochondrial pathways. Here, we investigate the effects of modulating NRF2 activity in neurons isolated from a A53T α-synuclein (A53TSyn) mouse model of synucleinopathy. Embryonic hippocampal neurons were isolated from A53TSyn mice and their wild type (WT) littermates. Neurons were treated with either the NRF2 activator dimethyl fumarate (DMF) or the NRF2 inhibitor ML385. Reactive oxygen species (ROS), dendritic arborization and dendritic spine density were quantified. Mitochondrial bioenergetics were also profiled in these neurons. A53TSyn neurons had increased ROS and reduced basal and maximal mitochondrial respiration relative to WT neurons. A53TSyn neurons also displayed decreased dendritic arborization and reduced spine density. Treatment with DMF reduced ROS levels and improved both mitochondrial function and arborization, while inhibition of NRF2 with ML385 exacerbated these endpoints. Modulation of NRF2 activity had a significant effect on mitochondrial function, oxidative stress, and synaptic plasticity in A53TSyn neurons. These data suggest that NRF2 may be a viable target for therapeutic interventions in PD.

Download Full-text

Nonuniform Distribution and Contribution of P- and P/Q-Types Calcium Channels to Short-Term Inhibitory Synaptic Plasticity in Cultured Hippocampal Neurons

International Journal of Physiology and Pathophysiology ◽

10.1615/intjphyspathophys.v2.i3.60 ◽

2011 ◽

Vol 2 (3) ◽

pp. 259-268

Author(s):

Oksana P. Kolesnyk-Mizerna ◽

Svetlana A. Fedulova ◽

Nikolai S. Veselovsky

Keyword(s):

Synaptic Plasticity ◽

Calcium Channels ◽

Hippocampal Neurons ◽

Nonuniform Distribution ◽

Short Term ◽

Cultured Hippocampal Neurons

Download Full-text

Faculty Opinions recommendation of Presynaptic CaMKII is necessary for synaptic plasticity in cultured hippocampal neurons.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1008915.231499 ◽

2004 ◽

Author(s):

Robert Zucker

Keyword(s):

Synaptic Plasticity ◽

Hippocampal Neurons ◽

Cultured Hippocampal Neurons

Download Full-text

Signaling Pathways Involved in Antidepressant-Induced Cell Proliferation and Synaptic Plasticity

Current Pharmaceutical Design ◽

10.2174/13816128113196660736 ◽

2014 ◽

Vol 20 (23) ◽

pp. 3776-3794 ◽

Cited By ~ 18

Author(s):

Fuencisla Pilar-Cuellar ◽

Rebeca Vidal ◽

Alvaro Díaz ◽

Elena Castro ◽

Severiano Anjos ◽

...

Keyword(s):

Cell Proliferation ◽

Synaptic Plasticity ◽

Signaling Pathways

Download Full-text

Altered Gut Microbiota and Its Metabolites in Hypertension of Developmental Origins: Exploring Differences between Fructose and Antibiotics Exposure

International Journal of Molecular Sciences ◽

10.3390/ijms22052674 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2674

Author(s):

Chien-Ning Hsu ◽

Julie Y. H. Chan ◽

Kay L. H. Wu ◽

Hong-Ren Yu ◽

Wei-Chia Lee ◽

...

Keyword(s):

Gut Microbiota ◽

Negative Impact ◽

Short Chain Fatty Acids ◽

Normal Diet ◽

Male Offspring ◽

Sprague Dawley ◽

Minocycline Treatment ◽

High Fructose ◽

Induced Hypertension ◽

Pregnancy And Lactation

Gut microbiota-derived metabolites, in particular short chain fatty acids (SCFAs) and their receptors, are linked to hypertension. Fructose and antibiotics are commonly used worldwide, and they have a negative impact on the gut microbiota. Our previous study revealed that maternal high-fructose (HF) diet-induced hypertension in adult offspring is relevant to altered gut microbiome and its metabolites. We, therefore, intended to examine whether minocycline administration during pregnancy and lactation may further affect blood pressure (BP) programmed by maternal HF intake via mediating gut microbiota and SCFAs. Pregnant Sprague-Dawley rats received a normal diet or diet containing 60% fructose throughout pregnancy and lactation periods. Additionally, pregnant dams received minocycline (50 mg/kg/day) via oral gavage or a vehicle during pregnancy and lactation periods. Four groups of male offspring were studied (n = 8 per group): normal diet (ND), high-fructose diet (HF), normal diet + minocycline (NDM), and HF + minocycline (HFM). Male offspring were killed at 12 weeks of age. We observed that the HF diet and minocycline administration, both individually and together, causes the elevation of BP in adult male offspring, while there is no synergistic effect between them. Four groups displayed distinct enterotypes. Minocycline treatment leads to an increase in the F/B ratio, but decreased abundance of genera Lactobacillus, Ruminococcus, and Odoribacter. Additionally, minocycline treatment decreases plasma acetic acid and butyric acid levels. Hypertension programmed by maternal HF diet plus minocycline exposure is related to the increased expression of several SCFA receptors. Moreover, minocycline- and HF-induced hypertension, individually or together, is associated with the aberrant activation of the renin–angiotensin system (RAS). Conclusively, our results provide a new insight into the support of gut microbiota and its metabolite SCAFs in the developmental programming of hypertension and cast new light on the role of RAS in this process, which will help prevent hypertension programmed by maternal high-fructose and antibiotic exposure.

Download Full-text