Publications by authors named "Matthew E Glover"

13 Publications

  • Page 1 of 1

Perinatal SSRI Exposure Disrupts G Protein-coupled Receptor BAI3 in Developing Dentate Gyrus and Adult Emotional Behavior: Relevance to Psychiatric Disorders.

Neuroscience 2021 09 19;471:32-50. Epub 2021 Jul 19.

School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. Electronic address:

Selective serotonin reuptake inhibitor (SSRI) antidepressants are widely prescribed to pregnant women suffering with depression, although the long-term impact of these medications on exposed offspring are poorly understood. Perinatal SSRI exposure alters human offspring's neurodevelopment and increases risk for psychiatric illness in later life. Rodent studies suggest that perinatal SSRI-induced behavioral abnormalities are driven by changes in the serotonin system as well as epigenetic and transcriptomic changes in the developing hippocampus. A major gene altered by perinatal SSRI exposure is the G-protein coupled receptor Brain Angiogenesis Inhibitor 3 (BAI3). Our present study shows that perinatal exposure to the SSRI citalopram increases mRNA expression of Bai3 and related molecules (including its C1ql ligands) in the early postnatal dentate gyrus of male and female offspring. Transient Bai3 mRNA knockdown in perinatal SSRI-exposed dentate gyrus lessened behavioral consequences of perinatal SSRI exposure, leading to increased active stress coping. To determine translational implications of this work, we examined expression of BAI3 and related molecules in hippocampus and prefrontal cortex from patients that suffered with depression or schizophrenia relative to healthy control subjects. We found sex- and region-specific changes in mRNA expression of BAI3 and its ligands C1QL2 and C1QL3 in men and women with a history of psychiatric disorders compared to healthy controls. Together these results suggest that abnormal BAI3 signaling may contribute to molecular mechanisms that drive adverse effects of perinatal SSRI exposure, and show evidence for alterations of BAI3 signaling in the hippocampus of patients that suffer depression and schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2021.07.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384689PMC
September 2021

Modeling heritability of temperamental differences, stress reactivity, and risk for anxiety and depression: Relevance to research domain criteria (RDoC).

Eur J Neurosci 2021 Feb 24. Epub 2021 Feb 24.

School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.

Animal models provide important tools to study biological and environmental factors that shape brain function and behavior. These models can be effectively leveraged by drawing on concepts from the National Institute of Mental Health Research Domain Criteria (RDoC) Initiative, which aims to delineate molecular pathways and neural circuits that underpin behavioral anomalies that transcend psychiatric conditions. To study factors that contribute to individual differences in emotionality and stress reactivity, our laboratory utilized Sprague-Dawley rats that were selectively bred for differences in novelty exploration. Selective breeding for low versus high locomotor response to novelty produced rat lines that differ in behavioral domains relevant to anxiety and depression, particularly the RDoC Negative Valence domains, including acute threat, potential threat, and loss. Bred Low Novelty Responder (LR) rats, relative to their High Responder (HR) counterparts, display high levels of behavioral inhibition, conditioned and unconditioned fear, avoidance, passive stress coping, anhedonia, and psychomotor retardation. The HR/LR traits are heritable, emerge in the first weeks of life, and appear to be driven by alterations in the developing amygdala and hippocampus. Epigenomic and transcriptomic profiling in the developing and adult HR/LR brain suggest that DNA methylation and microRNAs, as well as differences in monoaminergic transmission (dopamine and serotonin in particular), contribute to their distinct behavioral phenotypes. This work exemplifies ways that animal models such as the HR/LR rats can be effectively used to study neural and molecular factors driving emotional behavior, which may pave the way toward improved understanding the neurobiological mechanisms involved in emotional disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejn.15158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382785PMC
February 2021

Resilience to Stress: Lessons from Rodents about Nature versus Nurture.

Neuroscientist 2021 Feb 10:1073858421989357. Epub 2021 Feb 10.

School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA.

Individual differences in human temperament influence how we respond to stress and can confer vulnerability (or resilience) to emotional disorders. For example, high levels of behavioral inhibition in children predict increased risk of mood and anxiety disorders in later life. The biological underpinnings of temperament are unknown, although improved understanding can offer insight into the pathogenesis of emotional disorders. Our laboratory has used a rat model of temperamental differences to study neurodevelopmental factors that lead to a highly inhibited, stress vulnerable phenotype. Selective breeding for high versus low behavioral response to novelty created two rat strains that exhibit dramatic behavior differences over multiple domains relevant to emotional disorders. Low novelty responder (bLR) rats exhibit high levels of behavioral inhibition, passive stress coping, anhedonia, decreased sociability and vulnerability to chronic stress compared to high novelty responders (bHRs). On the other hand, bHRs exhibit high levels of behavioral dis-inhibition, active coping, and aggression. This review article summarizes our work with the bHR/bLR model showing the developmental emergence of the bHR/bLR phenotypes, the role the environment plays in shaping it, and the involvement of epigenetic processes such as DNA methylation that mediate differences in emotionality and stress reactivity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1073858421989357DOI Listing
February 2021

Inborn differences in emotional behavior coincide with alterations in hypothalamic paraventricular motor projections.

Eur J Neurosci 2021 02 15;53(3):814-826. Epub 2020 Dec 15.

School of Neuroscience, Virginia Polytechnic Institute and State University (Virginia Tech), Blacksburg, VA, USA.

Integrated behavioral responses to emotionally salient stimuli require the concomitant activation of descending neural circuits that integrate physiological, affective, and motor responses to stress. Our previous work interrogated descending circuits in the brainstem and spinal cord that project to motor and sympathetic targets. The hypothalamic paraventricular nucleus (PVN), a key node of this circuitry, integrates multiple motor and sympathetic responses activated by stress. The present study sought to determine whether descending projections from the PVN to targets in muscle and adrenal gland are differentially organized in rats with inborn differences in emotionality and stress responsivity. We utilized retrograde transsynaptic tract-tracing with unique pseudorabies virus (PRV) recombinants that were injected into sympathectomized gastrocnemius muscle and adrenal gland in two rat models featuring inborn differences in emotional behavior. Our tract-tracing results revealed a significant decrease in the number of PVN neurons with poly-synaptic projections to the gastrocnemius in male Wistar Kyoto [WKY] rats (versus Sprague Dawley rats) and selectively bred Low Novelty Responder [bLR] rats (versus selectively bred High Novelty Responder [bHR] rats). These neuroanatomical differences mirrored behavioral observations showing that both WKY and bLR rats display marked inhibition of emotional motor responses in a variety of settings relative to their respective controls. Our findings suggest that, in male rodents, PVN poly-synaptic projections to skeletal muscle may regulate emotional motor and coping responses to stress. More broadly, perturbations in PVN motor circuitry may play a role in mediating psychomotor disturbances observed in depression or anxiety-related disorders.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejn.15065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902414PMC
February 2021

Rats bred for high anxiety exhibit distinct fear-related coping behavior, hippocampal physiology, and synaptic plasticity-related gene expression.

Hippocampus 2019 10 17;29(10):939-956. Epub 2019 Apr 17.

School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, Virginia.

The hippocampus is essential for learning and memory but also regulates emotional behavior. We previously identified the hippocampus as a major brain region that differs in rats bred for emotionality differences. Rats bred for low novelty response (LRs) exhibit high levels of anxiety- and depression-like behavior compared to high novelty responder (HR) rats. Manipulating the hippocampus of high-anxiety LR rats improves their behavior, although no work to date has examined possible HR/LR differences in hippocampal synaptic physiology. Thus, the current study examined hippocampal slice electrophysiology, dendritic spine density, and transcriptome profiling in HR/LR hippocampus, and compared performance on three hippocampus-dependent tasks: The Morris water maze, contextual fear conditioning, and active avoidance. Our physiology experiments revealed increased long-term potentiation (LTP) at CA3-CA1 synapses in HR versus LR hippocampus, and Golgi analysis found an increased number of dendritic spines in basal layer of CA1 pyramidal cells in HR versus LR rats. Transcriptome data revealed glutamate neurotransmission as the top functional pathway differing in the HR/LR hippocampus. Our behavioral experiments showed that HR/LR rats exhibit similar learning and memory capability in the Morris water maze, although the groups differed in fear-related tasks. LR rats displayed greater freezing behavior in the fear-conditioning task, and HR/LR rats adopted distinct behavioral strategies in the active avoidance task. In the active avoidance task, HRs avoided footshock stress by pressing a lever when presented with a warning cue; LR rats, on the other hand, waited until footshocks began before pressing the lever to stop them. Taken together, these findings concur with prior observations of HR rats generally exhibiting active stress coping behavior while LRs exhibit reactive coping. Overall, our current findings coupled with previous work suggest that HR/LR differences in stress reactivity and stress coping may derive, at least in part, from differences in the developing and adult hippocampus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/hipo.23092DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377203PMC
October 2019

Altered DNA Methylation in the Developing Brains of Rats Genetically Prone to High versus Low Anxiety.

J Neurosci 2019 04 25;39(16):3144-3158. Epub 2019 Jan 25.

School of Neuroscience,

There is growing evidence of abnormal epigenetic processes playing a role in the neurobiology of psychiatric disorders, although the precise nature of these anomalies remains largely unknown. To study neurobiological (including epigenetic) factors that influence emotionality, we use rats bred for distinct behavioral responses to novelty. Rats bred for low novelty response (low responder [LR]) exhibit high levels of anxiety- and depressive-like behavior compared with high novelty responder (HR) rats. Prior work revealed distinct limbic brain development in HR versus LR rats, including altered expression of genes involved in DNA methylation. This led us to hypothesize that DNA methylation differences in the developing brain drive the disparate HR/LR neurobehavioral phenotypes. Here we report altered DNA methylation markers (altered DNA methyltransferase protein levels and increased global DNA methylation levels) in the early postnatal amygdala of LR versus HR male rats. Next-generation sequencing methylome profiling identified numerous differentially methylated regions across the genome in the early postnatal HR/LR amygdala. We also contrasted methylation profiles of male HRs and LRs with a control rat strain that displays an intermediate behavioral phenotype relative to the HR/LR extremes; this revealed that the LR amygdalar methylome was abnormal, with the HR profile more closely resembling that of the control group. Finally, through two methylation manipulations in early life, we found that decreasing DNA methylation in the developing male and female amygdala improves adult anxiety- and depression-like behavior. These findings suggest that inborn DNA methylation differences play important roles in shaping brain development and lifelong emotional behavior. Epigenetic changes are biological mechanisms that regulate the expression and function of genes throughout the brain and body. DNA methylation, one type of epigenetic mechanism, is known to be altered in brains of psychiatric patients, which suggests a role for DNA methylation in the pathogenesis of psychiatric disorders, such as depression and anxiety. The present study examines brains of rats that display high versus low levels of anxiety- and depression-like behavior to investigate how neural DNA methylation levels differ in these animals and how such differences shape their emotional behavioral differences. Studying how epigenetic processes affect emotional behavior may improve our understanding of the neurobiology of psychiatric disorders and lead to improved treatments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1523/JNEUROSCI.1157-15.2019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6468100PMC
April 2019

Perinatal exposure to the SSRI paroxetine alters the methylome landscape of the developing dentate gyrus.

Eur J Neurosci 2019 07 28;50(2):1843-1870. Epub 2019 Jan 28.

School of Neuroscience, Virginia Tech, Blacksburg, Virginia.

Evidence in humans and rodents suggests that perinatal exposure to selective serotonin reuptake inhibitor (SSRI) antidepressants can have serious long-term consequences in offspring exposed in utero or infancy via breast milk. In spite of this, there is limited knowledge of how perinatal SSRI exposure impacts brain development and adult behaviour. Children exposed to SSRIs in utero exhibit increased internalizing behaviour and abnormal social behaviour between the ages of 3 and 6, and increased risk of depression in adolescence; however, the neurobiological changes underlying this behaviour are poorly understood. In rodents, perinatal SSRI exposure perturbs hippocampal gene expression and alters adult emotional behaviour (including increased depression-like behaviour). The present study demonstrates that perinatal exposure to the SSRI paroxetine leads to DNA hypomethylation and reduces DNA methyltransferase 3a (Dnmt3a) mRNA expression in the hippocampus during the second and third weeks of life. Next-generation sequencing identified numerous differentially methylated genomic regions, including altered methylation and transcription of several dendritogenesis-related genes. We then tested the hypothesis that transiently decreasing Dnmt3a expression in the early postnatal hippocampus would mimic the behavioural effects of perinatal SSRI exposure. We found that siRNA-mediated knockdown of Dnmt3a in the dentate gyrus during the second to third week of life produced greater depression-like behaviour in adult female (but not male) offspring, akin to the behavioural consequences of perinatal SSRI exposure. Overall, these data suggest that perinatal SSRI exposure may increase depression-like behaviours, at least in part, through reduced Dnmt3a expression in the developing hippocampus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ejn.14315DOI Listing
July 2019

Of rodents and humans: A comparative review of the neurobehavioral effects of early life SSRI exposure in preclinical and clinical research.

Int J Dev Neurosci 2016 Jun 7;51:50-72. Epub 2016 May 7.

Department of Psychiatry, University of Alabama-Birmingham, USA. Electronic address:

Selective serotonin reuptake inhibitors (SSRIs) have been a mainstay pharmacological treatment for women experiencing depression during pregnancy and postpartum for the past 25 years. SSRIs act via blockade of the presynaptic serotonin transporter and result in a transient increase in synaptic serotonin. Long-lasting changes in cellular function such as serotonergic transmission, neurogenesis, and epigenetics, are thought to underlie the therapeutic benefits of SSRIs. In recent years, though, growing evidence in clinical and preclinical settings indicate that offspring exposed to SSRIs in utero or as neonates exhibit long-lasting behavioral adaptions. Clinically, children exposed to SSRIs in early life exhibit increased internalizing behavior reduced social behavior, and increased risk for depression in adolescence. Similarly, rodents exposed to SSRIs perinatally exhibit increased traits of anxiety- or depression-like behavior. Furthermore, certain individuals appear to be more susceptible to early life SSRI exposure than others, suggesting that perinatal SSRI exposure may pose greater risks for negative outcome within certain populations. Although SSRIs trigger a number of intracellular processes that likely contribute to their therapeutic effects, early life antidepressant exposure during critical neurodevelopmental periods may elicit lasting negative effects in offspring. In this review, we cover the basic development and structure of the serotonin system, how the system is affected by early life SSRI exposure, and the behavioral outcomes of perinatal SSRI exposure in both clinical and preclinical settings. We review recent evidence indicating that perinatal SSRI exposure perturbs the developing limbic system, including altered serotonergic transmission, neurogenesis, and epigenetic processes in the hippocampus, which may contribute to behavioral domains (e.g., sociability, cognition, anxiety, and behavioral despair) that are affected by perinatal SSRI treatment. Identifying the molecular mechanisms that underlie the deleterious behavioral effects of perinatal SSRI exposure may highlight biological mechanisms in the etiology of mood disorders. Moreover, because recent studies suggest that certain individuals may be more susceptible to the negative consequences of early life SSRI exposure than others, understanding mechanisms that drive such susceptibility could lead to individualized treatment strategies for depressed women who are or plan to become pregnant.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijdevneu.2016.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4930157PMC
June 2016

Altered metabolic activity in the developing brain of rats predisposed to high versus low depression-like behavior.

Neuroscience 2016 Jun 12;324:469-484. Epub 2016 Mar 12.

Department of Psychiatry and Behavioral Neurobiology, 1720 7th Ave S., SC 745, University of Alabama-Birmingham AL, USA.

Individual differences in human temperament can increase the risk of psychiatric disorders like depression and anxiety. Our laboratory utilized a rat model of temperamental differences to assess neurodevelopmental factors underlying emotional behavior differences. Rats selectively bred for low novelty exploration (Low Responders, LR) display high levels of anxiety- and depression-like behavior compared to High Novelty Responder (HR) rats. Using transcriptome profiling, the present study uncovered vast gene expression differences in the early postnatal HR versus LR limbic brain, including changes in genes involved in cellular metabolism. These data led us to hypothesize that rats prone to high (versus low) anxiety/depression-like behavior exhibit distinct patterns of brain metabolism during the first weeks of life, which may reflect disparate patterns of synaptogenesis and brain circuit development. Thus, in a second experiment we examined activity of cytochrome C oxidase (COX), an enzyme responsible for ATP production and a correlate of metabolic activity, to explore functional energetic differences in the HR/LR early postnatal brain. We found that HR rats display higher COX activity in the amygdala and specific hippocampal subregions compared to LRs during the first 2 weeks of life. Correlational analysis examining COX levels across several brain regions and multiple early postnatal time points suggested desynchronization in the developmental timeline of the limbic HR versus LR brain during the first two postnatal weeks. These early divergent COX activity levels may reflect altered circuitry or synaptic activity in the early postnatal HR/LR brain, which could contribute to the emergence of their distinct behavioral phenotypes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neuroscience.2016.03.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4838574PMC
June 2016

Protective effects of chronic mild stress during adolescence in the low-novelty responder rat.

Stress 2016 20;19(1):133-8. Epub 2015 Nov 20.

a Department of Psychiatry and Behavioral Neurobiology .

Stress-elicited behavioral and physiologic responses vary widely across individuals and depend on a combination of environmental and genetic factors. Adolescence is an important developmental period when neural circuits that guide emotional behavior and stress reactivity are still maturing. A critical question is whether stress exposure elicits contrasting effects when it occurs during adolescence versus adulthood. We previously found that Sprague-Dawley rats selectively bred for low-behavioral response to novelty (bred Low Responders; bLRs) are particularly sensitive to chronic unpredictable mild stress (CMS) exposure in adulthood, which exacerbates their typically high levels of spontaneous depressive- and anxiety-like behavior. Given developmental processes known to occur during adolescence, we sought to determine whether the impact of CMS on bLR rats is equivalent when they are exposed to it during adolescence as compared with adulthood. Young bLR rats were either exposed to CMS or control condition from postnatal days 35-60. As adults, we found that CMS-exposed bLRs maintained high levels of sucrose preference and exhibited increased social exploration along with decreased immobility on the forced swim test compared with bLR controls. These data indicate a protective effect of CMS exposure during adolescence in bLR rats.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3109/10253890.2015.1108304DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4903024PMC
September 2016

Maternal Style Selectively Shapes Amygdalar Development and Social Behavior in Rats Genetically Prone to High Anxiety.

Dev Neurosci 2015 17;37(3):203-14. Epub 2015 Mar 17.

Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, Ala., USA.

The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations. © 2015 S. Karger AG, Basel.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000374108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485591PMC
March 2016

DNA methylation markers in the postnatal developing rat brain.

Brain Res 2013 Oct 14;1533:26-36. Epub 2013 Aug 14.

Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL, USA.

In spite of intense interest in how altered epigenetic processes including DNA methylation may contribute to psychiatric and neurodevelopmental disorders, there is a limited understanding of how methylation processes change during early postnatal brain development. The present study used in situ hybridization to assess mRNA expression for the three major DNA methyltranserases (DNMTs)--DNMT1, DNMT3a and DNMT3b--in the developing rat brain at seven developmental timepoints: postnatal days (P) 1, 4, 7, 10, 14, 21, and 75. We also assessed 5-methylcytosine levels (an indicator of global DNA methylation) in selected brain regions during the first three postnatal weeks. DNMT1, DNMT3a and DNMT3b mRNAs are widely expressed throughout the adult and postnatal developing rat brain. Overall, DNMT mRNA levels reached their highest point in the first week of life and gradually decreased over the first three postnatal weeks within the hippocampus, amygdala, striatum, cingulate and lateral septum. Global DNA methylation levels did not follow this developmental pattern; methylation levels gradually increased over the first three postnatal weeks in the hippocampus, and remained stable in the developing amygdala and prefrontal cortex. Our results contribute to a growing understanding of how DNA methylation markers unfold in the developing brain, and highlight how these developmental processes may differ within distinct brain regions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2013.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3838910PMC
October 2013

Expression of klotho mRNA and protein in rat brain parenchyma from early postnatal development into adulthood.

Brain Res 2013 Aug 6;1527:1-14. Epub 2013 Jul 6.

Department of Psychiatry and Behavioral Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294-2182, USA.

Without the age-regulating protein klotho, mouse lifespan is shortened and the rapid onset of age-related disorders occurs. Conversely, overexpression of klotho extends mouse lifespan. Klotho is most abundant in kidney and expressed in a limited number of other organs, including the brain, where klotho levels are highest in choroid plexus. Reports vary on where klotho is expressed within the brain parenchyma, and no data is available as to whether klotho levels change across postnatal development. We used in situ hybridization to map klotho mRNA expression in the developing and adult rat brain and report moderate, widespread expression across grey matter regions. mRNA expression levels in cortex, hippocampus, caudate putamen, and amygdala decreased during the second week of life and then gradually rose to adult levels by postnatal day 21. Immunohistochemistry revealed a protein expression pattern similar to the mRNA results, with klotho protein expressed widely throughout the brain. Klotho protein co-localized with both the neuronal marker NeuN, as well as, oligodendrocyte marker olig2. These results provide the first anatomical localization of klotho mRNA and protein in rat brain parenchyma and demonstrate that klotho levels vary during early postnatal development.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.brainres.2013.06.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3756829PMC
August 2013
-->