scholarly journals Circuit Integration Initiation of New Hippocampal Neurons in the Adult Brain

Cell Reports ◽  
2020 ◽  
Vol 30 (4) ◽  
pp. 959-968.e3 ◽  
Author(s):  
Chih-Hao Yang ◽  
Adrian Di Antonio ◽  
Gregory W. Kirschen ◽  
Parul Varma ◽  
Jenny Hsieh ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Adult Brain ◽  
Circuit Integration

scholarly journals Telomerase increasing compound protects hippocampal neurons from amyloid beta toxicity by enhancing the expression of neurotrophins and plasticity related genes

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Natalie Baruch-Eliyahu ◽  
Vladislav Rud ◽  
Alex Braiman ◽  
Esther Priel
Keyword(s):  
Oxidative Stress ◽  
Amyloid Beta ◽  
Neurotrophic Factors ◽  
Hippocampal Neurons ◽  
Neuroprotective Effect ◽  
Adult Brain ◽  
Beta Catenin ◽  
Adult Mice ◽  
Hippocampal Cell Culture ◽  
Neuronal Degradation

AbstractThe telomerase reverse transcriptase protein, TERT, is expressed in the adult brain and its exogenic expression protects neurons from oxidative stress and from the cytotoxicity of amyloid beta (Aβ). We previously showed that telomerase increasing compounds (AGS) protected neurons from oxidative stress. Therefore, we suggest that increasing TERT by AGS may protect neurons from the Aβ-induced neurotoxicity by influencing genes and factors that participate in neuronal survival and plasticity. Here we used a primary hippocampal cell culture exposed to aggregated Aβ and hippocampi from adult mice. AGS treatment transiently increased TERT gene expression in hippocampal primary cell cultures in the presence or absence of Aβ and protected neurons from Aβ induced neuronal degradation. An increase in the expression of Growth associated protein 43 (GAP43), and Feminizing locus on X-3 genes (NeuN), in the presence or absence of Aβ, and Synaptophysin (SYP) in the presence of Aβ was observed. GAP43, NeuN, SYP, Neurotrophic factors (NGF, BDNF), beta-catenin and cyclin-D1 expression were increased in the hippocampus of AGS treated mice. This data suggests that increasing TERT by pharmaceutical compounds partially exerts its neuroprotective effect by enhancing the expression of neurotrophic factors and neuronal plasticity genes in a mechanism that involved Wnt/beta-catenin pathway.

scholarly journals Cacna1c: Protecting young hippocampal neurons in the adult brain

Neurogenesis ◽  
2016 ◽  
Vol 3 (1) ◽  
pp. e1231160 ◽  
Author(s):  
Héctor De Jesús-Cortés ◽  
Anjali M. Rajadhyaksha ◽  
Andrew A. Pieper
Keyword(s):  
Hippocampal Neurons ◽  
Adult Brain

scholarly journals Cloning and Characterization of Rat Caspase-9: Implications for a Role in Mediating Caspase-3 Activation and Hippocampal Cell Death after Transient Cerebral Ischemia

2002 ◽  
Vol 22 (5) ◽  
pp. 534-546 ◽  
Author(s):  
Guodong Cao ◽  
Yumin Luo ◽  
Tetsuya Nagayama ◽  
Wei Pei ◽  
R. Anne Stetler ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Hippocampal Neurons ◽  
Caspase 3 ◽  
Neuronal Survival ◽  
Global Ischemia ◽  
Adult Brain ◽  
Caspase 8 ◽  
Intrinsic Pathway ◽  
Caspase 9 ◽  
Transient Global Ischemia

Delayed hippocampal neurodegeneration after transient global ischemia is mediated, at least in part, through the activation of terminal caspases, particularly caspase-3, and the subsequent proteolytic degradation of critical cellular proteins. Caspase-3 may be activated by the membrane receptor-initiated caspase-8–dependent extrinsic pathway and the mitochondria-initiated caspase-9–dependent intrinsic pathway; however, the precise role of these deduced apoptosis-signaling pathways in activating caspase-3 in ischemic neurons remains elusive. The authors cloned the caspase-9 gene from the rat brain and investigated its potential role in mediating ischemic neuronal death in a rat model of transient global ischemia. Caspase-9 gene expression and protease activity were extremely low in the adult brain, whereas they were developmentally upregulated in newborn rats, especially at postnatal 12 weeks, a finding consistent with the theory of an essential role for caspase-9 in neuronal apoptosis during brain development. After 15-minute transient global ischemia, caspase-9 was overexpressed and proteolytically activated in the hippocampal CA1 neurons at 8 to 72 hours of reperfusion. The temporal profile of caspase-9 activation coincided with that of cytochrome c release and caspase-3 activation, but preceded CA1 neuronal death. Immunoprecipitation experiments revealed that there was enhanced formation of Apaf-1/caspase-9 complex in the hippocampus 8 and 24 hours after ischemia. Furthermore, intracerebral ventricular infusion of the relatively specific caspase-9 inhibitor N-benzyloxycarbonyl-Leu-Glu-His-Asp-fluoro-methylketone before ischemia attenuated caspase-3–like activity and significantly enhanced neuronal survival in the CA1 sector. In contrast, inhibition of caspase-8 activity had no significant effect on caspase-3 activation or neuronal survival. These results suggest that the caspase-9–dependent intrinsic pathway may be the primary mechanism responsible for the activation of caspase-3 in ischemic hippocampal neurons.

scholarly journals Upregulation of Neuronal Rheb(S16H) for Hippocampal Protection in the Adult Brain

2020 ◽  
Vol 21 (6) ◽  
pp. 2023 ◽  
Author(s):  
Gyeong Joon Moon ◽  
Minsang Shin ◽  
Sang Ryong Kim
Keyword(s):  
Hippocampal Neurons ◽  
Energy Homeostasis ◽  
Therapeutic Potential ◽  
Active Form ◽  
Mammalian Target Of Rapamycin ◽  
Adult Brain ◽  
Acid Uptake ◽  
Neuroprotective Effects ◽  
Virus Serotype ◽  
Mtorc1 Signaling

Ras homolog protein enriched in brain (Rheb) is a key activator of mammalian target of rapamycin complex 1 (mTORC1). The activation of mTORC1 by Rheb is associated with various processes such as protein synthesis, neuronal growth, differentiation, axonal regeneration, energy homeostasis, autophagy, and amino acid uptake. In addition, Rheb–mTORC1 signaling plays a crucial role in preventing the neurodegeneration of hippocampal neurons in the adult brain. Increasing evidence suggests that the constitutive activation of Rheb has beneficial effects against neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Our recent studies revealed that adeno-associated virus serotype 1 (AAV1) transduction with Rheb(S16H), a constitutively active form of Rheb, exhibits neuroprotective properties through the induction of various neurotrophic factors, promoting neurotrophic interactions between neurons and astrocytes in the hippocampus of the adult brain. This review provides compelling evidence for the therapeutic potential of AAV1–Rheb(S16H) transduction in the hippocampus of the adult brain by exploring its neuroprotective effects and mechanisms.

scholarly journals Sonic Hedgehog is expressed by hilar mossy cells and regulates cellular survival and neurogenesis in the adult hippocampus

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Luis E. Gonzalez-Reyes ◽  
Chia-Chu Chiang ◽  
Mingming Zhang ◽  
Joshua Johnson ◽  
Manuel Arrillaga-Tamez ◽  
...  
Keyword(s):  
Dentate Gyrus ◽  
Sonic Hedgehog ◽  
Hippocampal Neurons ◽  
Hippocampal Neurogenesis ◽  
Adult Brain ◽  
Cellular Survival ◽  
Mossy Cells ◽  
Cellular Source ◽  
Dynamic Source ◽  
Hilar Neurons

AbstractSonic hedgehog (Shh) is a multifunctional signaling protein governing pattern formation, proliferation and cell survival during embryogenesis. In the adult brain, Shh has neurotrophic function and is implicated in hippocampal neurogenesis but the cellular source of Shh in the hippocampus remains ill defined. Here, we utilize a gene expression tracer allele of Shh (Shh-nlacZ) which allowed the identification of a subpopulation of hilar neurons known as mossy cells (MCs) as a prominent and dynamic source of Shh within the dentate gyrus. AAV-Cre mediated ablation of Shh in the adult dentate gyrus led to a marked degeneration of MCs. Conversely, chemical stimulation of hippocampal neurons using the epileptogenic agent kainic acid (KA) increased the number of Shh+ MCs indicating that the expression of Shh by MCs confers a survival advantage during the response to excitotoxic insults. In addition, ablation of Shh in the adult dentate gyrus led to increased neural precursor cell proliferation and their migration into the subgranular cell layer demonstrating that MCs-generated Shh is a key modulator of hippocampal neurogenesis.

scholarly journals CD44: a novel synaptic cell adhesion molecule regulating structural and functional plasticity of dendritic spines

2016 ◽  
Vol 27 (25) ◽  
pp. 4055-4066 ◽  
Author(s):  
Matylda Roszkowska ◽  
Anna Skupien ◽  
Tomasz Wójtowicz ◽  
Anna Konopka ◽  
Adam Gorlewicz ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Dendritic Spines ◽  
Dendritic Spine ◽  
Rho Gtpases ◽  
Hippocampal Neurons ◽  
Synaptic Function ◽  
Adult Brain ◽  
Spine Shape ◽  
Neuronal Stimulation ◽  
And Function

Synaptic cell adhesion molecules regulate signal transduction, synaptic function, and plasticity. However, their role in neuronal interactions with the extracellular matrix (ECM) is not well understood. Here we report that the CD44, a transmembrane receptor for hyaluronan, modulates synaptic plasticity. High-resolution ultrastructural analysis showed that CD44 was localized at mature synapses in the adult brain. The reduced expression of CD44 affected the synaptic excitatory transmission of primary hippocampal neurons, simultaneously modifying dendritic spine shape. The frequency of miniature excitatory postsynaptic currents decreased, accompanied by dendritic spine elongation and thinning. These structural and functional alterations went along with a decrease in the number of presynaptic Bassoon puncta, together with a reduction of PSD-95 levels at dendritic spines, suggesting a reduced number of functional synapses. Lack of CD44 also abrogated spine head enlargement upon neuronal stimulation. Moreover, our results indicate that CD44 contributes to proper dendritic spine shape and function by modulating the activity of actin cytoskeleton regulators, that is, Rho GTPases (RhoA, Rac1, and Cdc42). Thus CD44 appears to be a novel molecular player regulating functional and structural plasticity of dendritic spines.

scholarly journals NRP/B, a Novel Nuclear Matrix Protein, Associates With p110RB and Is Involved in Neuronal Differentiation

1998 ◽  
Vol 141 (3) ◽  
pp. 553-566 ◽  
Author(s):  
Tae-Aug Kim ◽  
Jinkyu Lim ◽  
Setsuo Ota ◽  
Sandhya Raja ◽  
Rick Rogers ◽  
...  
Keyword(s):  
Neuronal Differentiation ◽  
Nuclear Matrix ◽  
Hippocampal Neurons ◽  
Matrix Protein ◽  
Neuroblastoma Cells ◽  
Adult Brain ◽  
Nuclear Matrix Protein ◽  
Neuronal Process ◽  
Process Formation ◽  
Primary Hippocampal Neurons

The nuclear matrix is defined as the insoluble framework of the nucleus and has been implicated in the regulation of gene expression, the cell cycle, and nuclear structural integrity via linkage to intermediate filaments of the cytoskeleton. We have discovered a novel nuclear matrix protein, NRP/B (nuclear restricted protein/brain), which contains two major structural elements: a BTB domain–like structure in the predicted NH2 terminus, and a “kelch motif” in the predicted COOH-terminal domain. NRP/B mRNA (5.5 kb) is predominantly expressed in human fetal and adult brain with minor expression in kidney and pancreas. During mouse embryogenesis, NRP/B mRNA expression is upregulated in the nervous system. The NRP/B protein is expressed in rat primary hippocampal neurons, but not in primary astrocytes. NRP/B expression was upregulated during the differentiation of murine Neuro 2A and human SH-SY5Y neuroblastoma cells. Overexpression of NRP/B in these cells augmented neuronal process formation. Treatment with antisense NRP/B oligodeoxynucleotides inhibited the neurite development of rat primary hippocampal neurons as well as the neuronal process formation during neuronal differentiation of PC-12 cells. Since the hypophosphorylated form of retinoblastoma protein (p110RB) is found to be associated with the nuclear matrix and overexpression of p110RB induces neuronal differentiation, we investigated whether NRP/B is associated with p110RB. Both in vivo and in vitro experiments demonstrate that NRP/B can be phosphorylated and can bind to the functionally active hypophosphorylated form of the p110RB during neuronal differentiation of SH-SY5Y neuroblastoma cells induced by retinoic acid. Our studies indicate that NRP/B is a novel nuclear matrix protein, specifically expressed in primary neurons, that interacts with p110RB and participates in the regulation of neuronal process formation.

scholarly journals Functional integration of new hippocampal neurons following insults to the adult brain is determined by characteristics of pathological environment

2011 ◽  
Vol 229 (2) ◽  
pp. 484-493 ◽  
Author(s):  
James C. Wood ◽  
Johanna S. Jackson ◽  
Katherine Jakubs ◽  
Katie Z. Chapman ◽  
Christine T. Ekdahl ◽  
...  
Keyword(s):  
Hippocampal Neurons ◽  
Functional Integration ◽  
Adult Brain ◽  
Pathological Environment

scholarly journals Tet1 isoforms differentially regulate gene expression, synaptic transmission and memory in the mammalian brain

2020 ◽  
Author(s):  
C.B. Greer ◽  
J. Wright ◽  
J.D. Weiss ◽  
R.M. Lazerenko ◽  
S.P. Moran ◽  
...  
Keyword(s):  
Synaptic Transmission ◽  
Hippocampal Neurons ◽  
Dna Demethylation ◽  
Adult Brain ◽  
Mammalian Brain ◽  
Dynamic Regulation ◽  
Regulate Gene Expression ◽  
Active Dna Demethylation ◽  
Cell Type Specific ◽  
The Individual

The dynamic regulation of DNA methylation in post-mitotic neurons is necessary for memory formation and other adaptive behaviors. Ten-eleven translocation 1 (TET1) plays a part in these processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby initiating active DNA demethylation. However, attempts to pinpoint its exact role in the nervous system have been hindered by contradictory findings, perhaps due in part, to a recent discovery that two isoforms of the Tet1 gene are differentially expressed from early development into adulthood. Here, we demonstrate that both the shorter transcript (Tet1S) encoding an N-terminally truncated TET1 protein and a full-length Tet1 (Tet1FL) transcript encoding canonical TET1 are co-expressed in the adult brain. We show that Tet1S is the predominantly expressed isoform, and is highly enriched in neurons, whereas Tet1FL is generally expressed at lower levels and more abundant in glia, suggesting their roles are at least partially cell-type specific. Using viral-mediated, isoform- and neuron-specific molecular tools, we find that Tet1S repression enhances, while Tet1FL impairs, hippocampal-dependent memory. In addition, the individual disruption of the two isoforms leads to contrasting changes in basal synaptic transmission and the dysregulation of unique gene ensembles in hippocampal neurons. Together, our findings demonstrate that each Tet1 isoform serves a distinct role in the mammalian brain.

scholarly journals Fluorometric Determination of Glucose Utilization in Neurons in Vitro and in Vivo

2004 ◽  
Vol 24 (9) ◽  
pp. 993-1003 ◽  
Author(s):  
Yoshiaki Itoh ◽  
Takato Abe ◽  
Rie Takaoka ◽  
Norio Tanahashi
Keyword(s):  
Energy Source ◽  
Hippocampal Neurons ◽  
Glucose Utilization ◽  
Adult Brain ◽  
Sprague Dawley ◽  
Extracellular Lactate ◽  
Major Energy Source ◽  
Cerebellar Purkinje Cells

Glucose is the major energy source the adult brain utilizes under physiologic conditions. Recent findings, however, have suggested that neurons obtain most of their energy from the oxidation of extracellular lactate derived from astroglial metabolism of glucose transported into the brain from the blood. In the present studies we have used 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), a fluorescent analogue of 2-deoxyglucose, which is often used to trace glucose utilization in neural tissues, to examine glucose metabolism in neurons in vitro and in vivo. Cultured neurons and astroglia were incubated with 2-NBDG for up to 15 minutes, and nonmetabolized 2-NBDG was washed out. We found that fluorescence intensity increased linearly with incubation time in both neurons and astroglia, indicating that both types of brain cells could utilize glucose as their energy source in vitro. To determine if the same were true in vivo, Sprague-Dawley rats were injected intravenously with a pulse bolus of 2-NBDG and decapitated 45 minutes later. Examination of brain sections demonstrated that phosphorylated 2-NBDG accumulated in hippocampal neurons and cerebellar Purkinje cells, indicating that neurons can utilize glucose in vivo as energy source.

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