Postpubertal decrease in hippocampal dendritic spines of female rats

Yıldırım, Murat; Mapp, Oni M.; Janssen, William G.M.; Yin, Wang; Morrison, John H.; Gore, Andrea C.

doi:10.1016/j.expneurol.2007.11.003

Cited by 35 publications

(24 citation statements)

References 73 publications

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“…Axons, dendrites, synapses and synaptic receptors are modified in several brain regions between puberty and adulthood (Sisk and Zehr, 2005). In general, studies in animals are in agreement with the observations in humans, indicating that there is a reorganization of neuronal connectivity in the grey matter after puberty (Anderson et al, 1995; Meyer et al, 1978; Yildirim et al, 2008). In addition, the pattern of neuronal/dendritic proliferation varies with the cortical/neocortical region (i.e., medial prefrontal cortex, hippocampus) being examined in a sex-dependent manner (Juraska et al, 1985, 1989; Markham et al, 2007).…”

Section: Framework For Gender Differences In Adolescent Neurobiologysupporting

confidence: 84%

Framework for sex differences in adolescent neurobiology: A focus on cannabinoids

Viveros

Marco

López‐Gallardo

et al. 2011

Neuroscience & Biobehavioral Reviews

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This review highlights the salient findings that have furthered our understanding of how sex differences are initiated during development and maintained throughout life. First we discuss how gonadal steroid hormones organize the framework for sex differences within critical periods of development—namely, during those exposures which occur in utero and post-partum, as well as those which occur during puberty. Given the extensive precedence of sex differences in cannabinoid-regulated biology, we then focus on the disparities within the endogenous cannabinoid system, as well as those observed with exogenously administered cannabinoids. We start with how the expression of cannabinoid CB1 receptors is regulated throughout development. This is followed by a discussion of differential vulnerability to the pathological sequelae stemming from cannabinoid exposure during adolescence. Next we talk about sex differences in the interactions between cannabinoids and other drugs of abuse, followed by the organizational and activational roles of gonadal steroids in establishing and maintaining the sex dependence in the biological actions of cannabinoids. Finally, we discuss ways to utilize this knowledge to strategically target critical developmental windows of vulnerability/susceptibility and thereby implement more effective therapeutic interventions for afflictions that may be more prevalent in one sex vs. the other.

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Section: Framework For Gender Differences In Adolescent Neurobiologysupporting

confidence: 84%

Framework for sex differences in adolescent neurobiology: A focus on cannabinoids

Viveros

Marco

López‐Gallardo

et al. 2011

Neuroscience & Biobehavioral Reviews

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“…For example, neurogenesis and the density of dendritic spines are higher in early adolescence and begin to decline to adult levels soon after puberty (He and Crews, 2007;Yildirim et al, 2008). There is evidence of differences in signaling cascades in adolescents compared to adults, with changes in the composition of signaling proteins in the hippocampus occurring in adolescence (Weitzdorfer et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood

McCormick¹,

Thomas²,

Sheridan³

et al. 2011

Hippocampus

105

127

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The ongoing development of the hippocampus in adolescence may be vulnerable to stressors. The effects of social instability stress (SS) in adolescence (daily 1 h isolation and change of cage partner postnatal days 30-45) on cell proliferation in the dentate gyrus (DG) in adolescence (on days 33 and 46, experiment 1) and in adulthood (experiment 2) was examined in Long Evans male rats and compared to nonstressed controls (CTL). Additionally, in experiment 2, a separate group of SS and CTL rats was tested on either a spatial (hippocampal-dependent) or nonspatial (nonhippocampal dependent) version of an object memory test and also were used to investigate hippocampal expression of markers of synaptic plasticity. No memory impairment was evident until the SS rats were adults, and the impairment was only on the spatial test. SS rats initially (postnatal day 33) had increased cell proliferation based on counts of Ki67 immunoreactive (ir) cells and greater survival of immature neurons based on counts of doublecortin ir cells on day 46 and in adulthood, irrespective of behavioral testing. Counts of microglia in the DG did not differ by stress group, but behavioral testing was associated with reduced microglia counts compared to nontested rats. As adults, SS and CTL rats did not differ in hippocampal expression of synaptophysin, but compared to CTL rats, SS rats had higher expression of basal calcium/calmodulin-dependent kinase II (CamKII), and lower expression of the phosphorylated CamKII subunit threonine 286, signaling molecules related to synaptic plasticity. The results are contrasted with those from previous reports of chronic stress in adult rats, and we conclude that adolescent stress alters the ongoing development of the hippocampus leading to impaired spatial memory in adulthood, highlighting the heightened vulnerability to stressors in adolescence.

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“…Adolescent synaptic pruning is seen in many CNS areas (Huttenlocher, 1979, Zehr et al, 2006, Yildirim et al, 2008, Petanjek et al, 2011, Drzewiecki et al, 2016) including prefrontal cortex and amygdala, in addition to CA1 hippocampus, and is associated with EEG changes in humans (Campbell et al, 2012). Pubertal expression of α4βδ GABARs may serve to sculpt the hippocampal circuit, reducing synapses which are no longer relevant to allow for new synaptic connections as the animal reaches adulthood.…”

Section: Discussionmentioning

confidence: 99%

“…Adolescent synaptic pruning occurs throughout the CNS (Huttenlocher, 1979, Zehr et al, 2006, Yildirim et al, 2008, Drzewiecki et al, 2016) and may be necessary for optimal cognition (Chechik et al, 1999). Synaptic pruning is also thought to play a pivotal role in the etiology of developmental disorders including schizophrenia and autism (Glantz and Lewis, 2000, Hutsler and Zhang, 2010) where the hippocampus is a common region associated with both disorders (Schumann et al, 2004, Steen et al, 2006) and where there is a suggested link between optimal synapse number and cognition.…”

mentioning

confidence: 99%

α4βδ GABAA receptors reduce dendritic spine density in CA1 hippocampus and impair relearning ability of adolescent female mice: Effects of a GABA agonist and a stress steroid

2017

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Synaptic pruning underlies the transition from an immature to an adult CNS through refinements of neuronal circuits. Our recent study indicates that pubertal synaptic pruning is triggered by the inhibition generated by extrasynaptic α4βδ GABAA receptors (GABARs) which are increased for 10 d on dendritic spines of CA1 pyramidal cells at the onset of puberty (PND 35–44) in the female mouse, suggesting α4βδ GABARs as a novel target for the regulation of adolescent synaptic pruning. In the present study we used a pharmacological approach to further examine the role of these receptors in altering spine density during puberty of female mice and the impact of these changes on spatial learning, assessed in adulthood. Two drugs were chronically administered during the pubertal period (PND 35–44): the GABA agonist gaboxadol (GBX, 0.1 mg/kg, i.p.), to enhance current gated by α4βδ GABARs and the neurosteroid/stress steroid THP (3α-OH-5β-pregnan-20-one, 10 mg/kg, i.p.) to decrease expression of α4βδ. Spine density was determined on PND 56 with Golgi staining. Spatial learning and relearning were assessed using the multiple object relocation task (MPORT) and an active place avoidance task (APA) on PND 56. Pubertal GBX decreased spine density post-pubertally by 70% (P<0.05), while decreasing α4βδ expression with THP increased spine density by two-fold (P<0.05), in both cases, with greatest effects on the mushroom spines. Adult relearning ability was compromised in both hippocampus-dependent tasks after pubertal administration of either drug. These findings suggest that an optimal spine density produced by α4βδ GABARs is necessary for optimal cognition in adults.

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Postpubertal decrease in hippocampal dendritic spines of female rats

Cited by 35 publications

References 73 publications

Framework for sex differences in adolescent neurobiology: A focus on cannabinoids

Framework for sex differences in adolescent neurobiology: A focus on cannabinoids

Social instability stress in adolescent male rats alters hippocampal neurogenesis and produces deficits in spatial location memory in adulthood

α4βδ GABAA receptors reduce dendritic spine density in CA1 hippocampus and impair relearning ability of adolescent female mice: Effects of a GABA agonist and a stress steroid

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