rapid-golgi-stain-for-dendritic-spine-visualization-hippocampus

Rapid Golgi Stain for Dendritic Spine Visualization in Hippocampus and Prefrontal Cortex

Golgi impregnation, using the Golgi staining kit with minor adaptations, is used to impregnate dendritic spines in the rat hippocampus and medial ...

Sacred Heart University

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Increasing evidence suggests that the time course of advantageous versus deleterious effects of stress on physiologic function is also apparent in some brain functions, including learning and memory. This article reviews the effects of chronic stress on behavioral performance and, more importantly, shows that sex of the subject, as well as duration and intensity of stress, is an important determinant of the functional/behavioral, neurochemical, and anatomical consequences of the stress. Following chronic stress (7-28 days of restraint, 6 h/day), male and female rats were tested on a visual memory task (object recognition) and two spatial memory tasks (object placement and radial arm maze). At 21 days, stress impaired males on all tasks while females were either enhanced (spatial memory tasks) or not impaired (nonspatial memory tasks). Additionally, the influence of the hypothalamic-pituitary-adrenocortical axis in mediating the sex-specific responses to stress is considered. Behavioral and neurochemical assessments following chronic stress in ovariectomized females, with and without estradiol, suggest that estrogen exerts both organizational and activational influences on the observed sex differences in response to stress. Furthermore, stress differentially affected central transmitter levels in the frontal cortex, hippocampus, and amygdala depending on sex. The possible role of these sex-specific changes in neurotransmitter levels in mediating behavioral differences in response to stress is discussed. While these results are thus far limited to a few studies and require both further investigation and verification, chronic stress appears to be associated with distinct, sex-differentiated behavioral/cognitive and neurochemical responses. We conclude that sex differences must be taken into account when investigating or describing stress and associated sequalae.

Chronic stress effects on memory: sex differences in performance and monoaminergic activity.

Plus en plus probantes sugg&egrave;re que l&#39;&eacute;volution temporelle de l&#39;avantageux par rapport aux effets n&eacute;fastes du stress sur la fonction physiologique est &eacute;galement apparente dans certaines fonctions c&eacute;r&eacute;brales, y compris l&#39;apprentissage et la m&eacute;moire. Cet article examine les effets du stress chronique sur la performance comportementale et, plus important encore, montre que le sexe de l&#39;objet, ainsi que la dur&eacute;e et l&#39;intensit&eacute; du stress, est un facteur d&eacute;terminant des cons&eacute;quences fonctionnelles et comportementales, neurochimiques et anatomiques de la contrainte. &Agrave; la suite de stress chronique (7-28 jours de retenue, 6 h/jour), des rats m&acirc;les et femelles ont &eacute;t&eacute; test&eacute;s sur une t&acirc;che de m&eacute;moire visuelle (reconnaissance d&#39;objet) et deux t&acirc;ches de m&eacute;moire spatiale (placement des objets et labyrinthe radial). &Agrave; 21 jours, les m&acirc;les stress r&eacute;duite sur toutes les t&acirc;ches, tandis que les femelles ont &eacute;t&eacute; que soit am&eacute;lior&eacute; (t&acirc;ches de m&eacute;moire spatiale) ou non alt&eacute;r&eacute;e (t&acirc;ches de m&eacute;moire non spatiales). En outre, l&#39;influence de l&#39;axe hypothalamique-pituitaire-corticosurr&eacute;nale dans la m&eacute;diation des r&eacute;ponses selon le sexe au stress est consid&eacute;r&eacute;. &Eacute;valuations comportementales et neurochimiques, suite &agrave; un stress chronique chez les femmes ayant subi une ovariectomie, avec et sans l&#39;estradiol, sugg&egrave;rent que &oelig;strog&egrave;ne exerce des influences organisationnelles et activational sur les diff&eacute;rences entre les sexes observ&eacute;es en r&eacute;ponse au stress. En outre, stress affect&eacute;es diff&eacute;remment niveaux &eacute;metteur central dans le cortex frontal, le hippocampe et l&#39;amygdale selon le sexe. On discute le r&ocirc;le possible de ces changements de sexe dans les niveaux de neurotransmetteurs dans la m&eacute;diation des diff&eacute;rences de comportement en r&eacute;ponse au stress. Bien que ces r&eacute;sultats sont jusqu&#39;&agrave; pr&eacute;sent limit&eacute;es &agrave; quelques &eacute;tudes et n&eacute;cessitent un examen plus pouss&eacute; et v&eacute;rification, stress chronique semble &ecirc;tre associ&eacute; avec les r&eacute;ponses neurochimiques et distinct, diff&eacute;renci&eacute;es par sexe comportemental et cognitif. Nous concluons que les diff&eacute;rences li&eacute;es au sexe doivent prendre en consid&eacute;ration lors de la recherche ou qui d&eacute;crit le stress et les s&eacute;quelles associ&eacute;es.

Effets du stress chronique sur la m&eacute;moire : diff&eacute;rences dans l&#39;activit&eacute; de performance et monoaminergiques sexuelles.

Chronischer Stress Auswirkungen auf Ged&#xE4;chtnis: Geschlecht Unterschiede in der Leistung und monoaminerge Aktivit&#xE4;t.

Crescente evidenza suggerisce che il corso di tempo della vantaggiosa contro gli effetti deleteri dello stress sulla funzione fisiologica &egrave; anche evidente in alcune funzioni cerebrali, tra cui l&#39;apprendimento e la memoria. Questo articolo recensioni gli effetti dello stress cronico sulle performance comportamentali e, soprattutto, dimostra che il sesso del soggetto, cos&igrave; come durata e intensit&agrave; dello sforzo, &egrave; un&#39;importante determinante delle conseguenze funzionali/comportamentale, neurochimica e anatomiche dello stress. A seguito di stress cronico (7-28 giorni di fermo, 6 ore al giorno), ratti maschi e femminili sono stati testati su un compito di memoria visiva (object recognition) e due compiti di memoria spaziale (oggetto di collocamento e labirinto a bracci radiali). A 21 giorni, i maschi con problemi di stress su tutte le attivit&agrave;, mentre le femmine erano che sia migliorata (compiti di memoria spaziale) o non vedenti (attivit&agrave; di nonspatial memoria). Inoltre, &egrave; considerato l&#39;influenza dell&#39;asse ipotalamico-pituitario-corticosurrenale nella mediazione il sesso-specifiche risposte allo stress. Valutazioni comportamentali e neurochimici seguendo lo stress cronico nelle femmine ovariectomizzati, con e senza estradiolo, suggeriscono che gli estrogeni esercitano influenze organizzative e activational sulle differenze di sesso osservati in risposta allo stress. Inoltre, lo stress differenzialmente interessati livelli trasmettitore centrale nella corteccia frontale, ippocampo e amigdala a seconda del sesso. Il possibile ruolo di questi sex-specific cambiamenti nei livelli di neurotrasmettitore nel mediare le differenze comportamentali in risposta allo stress &egrave; discusso. Mentre questi risultati sono finora limitati a pochi studi e necessitano di ulteriori indagini e verifica, lo stress cronico sembra essere associato con distinte, sesso-differenziato comportamentali/cognitive e risposte neurochemical. Concludiamo che le differenze di sesso devono tener conto quando indagare o descrivendo lo stress e sequalae associato.

Gli effetti dello stress cronico sulla memoria: le differenze di prestazioni e monoaminergic attivit&agrave; di sesso.

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&#xBA54;&#xBAA8;&#xB9AC;&#xC5D0; &#xB300; &#xD55C; &#xB9CC;&#xC131; &#xC2A4;&#xD2B8;&#xB808;&#xC2A4; &#xD6A8;&#xACFC;: &#xC139;&#xC2A4; &#xC131;&#xB2A5; &#xBC0F; monoaminergic &#xD65C;&#xB3D9;&#xC758; &#xCC28;&#xC774;.

Creciente evidencia sugiere que el curso del tiempo de ventajas frente a los efectos nocivos del estr&eacute;s en funci&oacute;n fisiol&oacute;gica es tambi&eacute;n evidente en algunas funciones del cerebro, incluyendo el aprendizaje y la memoria. Este art&iacute;culo Comentarios sobre los efectos del estr&eacute;s cr&oacute;nico en el rendimiento conductual y, m&aacute;s importante a&uacute;n, muestra que el sexo de la materia, as&iacute; como duraci&oacute;n e intensidad del estr&eacute;s, es un factor determinante de las consecuencias funcionales/comportamiento, neuroqu&iacute;micos y anat&oacute;micas de la tensi&oacute;n. Tras el estr&eacute;s cr&oacute;nico (7-28 d&iacute;as de inmovilizaci&oacute;n, 6 h/d&iacute;a), machos y hembras fueron probados en una tarea de memoria visual (reconocimiento del objeto) y dos tareas de memoria espacial (colocaci&oacute;n de objeto y laberinto radial del brazo). A los 21 d&iacute;as, los hombres con problemas de estr&eacute;s en todas las tareas, mientras que las hembras fueron que ya sea mejorada (tareas de memoria espacial) o no deterioraron (tareas de la memoria espacial). Adem&aacute;s, se considera la influencia del eje hipotal&aacute;mico-pituitario-adrenocortical en la mediaci&oacute;n de las respuestas al estr&eacute;s de sexo. Evaluaciones neuroqu&iacute;micas y conductuales tras estr&eacute;s cr&oacute;nico en las hembras ovariectomizadas, con y sin estradiol, sugieren que el estr&oacute;geno ejerce influencias tanto organizacionales y elevadas sobre las diferencias de sexo observado en respuesta al estr&eacute;s. Adem&aacute;s, estr&eacute;s afecta diferencialmente niveles de transmisor central en la corteza frontal, el hipocampo y la am&iacute;gdala seg&uacute;n sexo. Se discute la posible funci&oacute;n de estos cambios de sexo en los niveles de neurotransmisores en la mediaci&oacute;n de las diferencias de comportamiento en respuesta al estr&eacute;s. Si bien estos resultados hasta el momento se limitan a unos pocos estudios y requieren m&aacute;s investigaci&oacute;n y verificaci&oacute;n, estr&eacute;s cr&oacute;nico parece estar asociado con distintas, diferenciados por sexo comportamiento/cognitivas y respuestas neuroqu&iacute;micas. Se concluye que las diferencias de sexo deben tenerse en cuenta al investigar o estr&eacute;s y sequalae asociado.

Efectos del estr&eacute;s cr&oacute;nico en memoria: diferencias de g&eacute;nero en la actividad de rendimiento y monoamin&eacute;rgicos.

Exposure to stress during gestation results in physiological and behavioral alterations that persist into adulthood. This study examined the effects of prenatal stress on the postnatal expression of sexually differentiated cognitive, hormonal, and neurochemical profiles in male and female rats. Pregnant dams were subjected to restraint stress three times daily for 45 min during d 14-21 of pregnancy. The offspring of control and prenatally stressed dams were tested for anxiety-related and cognitive behaviors, stress and gonadal steroid hormone levels, as well as monoamines and metabolite levels in selected brain regions. Postnatal testosterone levels (measured at 1 and 5 d) did not differ between controls and prenatally stressed animals. In adulthood, the serum corticosterone response to stress was attenuated in prenatally stressed females, eliminating the sex difference normally observed in this parameter. Prenatally stressed females exhibited higher anxiety levels, evidenced by longer open field entry latencies. Prenatal stress had no effect on object recognition memory, but eliminated the advantage normally seen in the male performance of a spatial memory task. Neurochemical profiles of prenatally stressed females were altered toward the masculine phenotype in the prefrontal cortex, amygdala, and hippocampus. Thus, prenatal stress altered subsequent cognitive, endocrine, and neurochemical responses in a sex-specific manner. These data reinforce the view that prenatal stress affects multiple aspects of brain development, interfering with the expression of normal behavioral, neuroendocrine, and neurochemical sex differences. These data have implications for the effects of prenatal stress on the development of sexually dimorphic endocrine and neurological disorders.

Sexually dimorphic effects of prenatal stress on cognition, hormonal responses, and central neurotransmitters.

Stress exposure, depending on intensity and duration, elicits adaptive or maladaptive physiological changes. The same general pattern of advantageous versus deleterious stress effects appears to exist for some cognitive functions, particularly spatial learning and memory performance. This article reviews sex differences in response to stress on a variety of spatial tasks. In general, females are more resistant than males to stress-induced impairments on spatial tasks, including the radial arm maze and object placement. In young adulthood, chronic stress (restraint, 6 h per day for 21 days) impairs male performance on both tasks but leads to behavioural enhancements in females. Furthermore, these sex-dependent stress effects are influenced by both organisational and activational oestrogenic effects. Additionally, sex-specific stress responses vary depending on developmental age at the time of stress exposure. Male behavioural stress responses appear fixed across the lifespan (i.e. stress-induced cognitive impairments) whereas female stress responses appear more variable (i.e. stress-induced enhancements observed in young adulthood are different in response to prenatal stress and diminished following stress exposure at old age). These findings underscore the point that many effects obtained in males cannot be generalised to females and highlight the need to investigate the stress response at different ages and in both sexes.

Stress-induced changes in spatial memory are sexually differentiated and vary across the lifespan.

Cognitive, as well as physiological, sex differences exist in young adult rats under both basal conditions and following chronic stress; however, few studies have examined whether sex differences remain in aged subjects and whether responses to stress are altered. We compared aged male and female Fischer 344 rats (21.5 months at testing) without stress and when given 21 days of restraint for 6 h/day on locomotion, anxiety-related behaviors, object recognition (non-spatial memory), object placement (spatial memory), body weight and serum steroid hormone levels. Control (unstressed) females had lower levels of estradiol and testosterone and higher corticosterone than males, and stress had no lasting effect on hormone concentrations. Females weighed less than males and showed less weight loss with stress. Locomotion measures on an open field were similar in the sexes and unaffected by stress. Anxiety-related behavior measures on the field showed that males were generally more anxious and that stress increased male, but decreased, female anxiety-related behaviors. In memory testing, exploration of objects was not different between the sexes, with or without stress, while stress increased exploration in both sexes during object recognition trials. Both males and females, regardless of treatment, discriminated between old and new objects at short, but not long, inter-trial delays. The typical advantage of young males for spatial memory performance was not observed in aged subjects on the object placement tasks. Stress-dependent enhancements in females and impairments in males for object placement are reported for young rats, but in aged rats, neither sex was altered by stress. Current data suggest that aging is associated with changes in the pattern of sex differences present in young adult rats in some behaviors and in the behavioral responses to stress.

Aged rats: sex differences and responses to chronic stress.

Chronic restraint stress alters performance of rats on cognitive tasks, and anxiety measurements, and these stress-induced behavioral alterations are sexually dimorphic. Following a long stress period (21 days restraint) males show cognitive impairments while females are either not affected or enhanced on the same tasks. The current study examined whether sexually differentiated responses are also induced following shorter restraint stress durations. Male and female Sprague Dawley rats, aged 2.5 months, served as controls or received restraint stress (6 h/day, 7 days) and were tested for anxiety (plus maze), non-spatial memory (object recognition), and spatial memory (object placement). Plus maze performance was altered by sex and stress exposure. Stress impaired male object recognition but did not affect female performance. Stress did not affect male spatial memory; however, control females could not significantly discriminate between the old and new locations, but stress exposure enhanced female performance. Following behavioral testing, monoamines and metabolites were measured in prefrontal cortex (PFC), hippocampus (CA1, CA3), and amygdala. Notably, PFC and CA3 indices for noradrenergic activity (MHPG levels and MHPG/NE ratios) were increased in stress females, but decreased in males, and similar changes were found in CA1 and BLA dopaminergic indices. Thus, these sexually dimorphic neurochemical changes following stress may underlie the behavioral differences. Current results show that short-term restraint elicits sex-dependent behavioral and neural changes different from those previously reported for longer term stresses and suggest that the temporal relationship between the change from adaptive to maladaptive responses to stress is shorter in male than female rats.

Sex-dependent changes in anxiety, memory, and monoamines following one week of stress.

Stress, depending on intensity and duration, elicits adaptive or maladaptive physiological effects. Increasing evidence shows those patterns of advantageous versus deleterious physiologic stress effects also exist for some brain functions, including learning and memory. For example, short stress enhances, while chronic stress impairs, performance on numerous cognitive tasks in male rats. In contrast, performance of female rats is enhanced, or not altered, following both short-term and long-term stress exposure on the same behavioral tasks. The current study was designed to better characterize the behavioral effects of sustained chronic restraint stress in female rats. Female Sprague Dawley rats were assigned to a stress (restraint, 6 h/day, 35 days) or control (no stress) condition, weighed weekly, and then tested on open field (OF), object recognition (OR) and object placement (OP) tasks. Stressed females gained less weight during stress than controls. On the OF, there were no group differences in locomotor activity, but stressed females made fewer inner visits than controls, indicating increased anxiety. Both groups successfully performed the OP and OR tasks across all inter-trial delays, indicating intact non-spatial and spatial memory in both control and stress females. The current results provide preliminary evidence that the commonly used chronic restraint stress model may not be an efficient stressor to female rats.

Chronically stressed female rats show increased anxiety but no behavioral alterations in object recognition or placement memory: a preliminary examination.

The endocrine disruptor Bisphenol-A (BPA) has been shown to modulate estrogenic, androgenic, and anti-androgenic effects. The effects of BPA exposure during early organizational periods of development have been well documented. The current study focuses on the effects of short term, low-dose BPA exposure on anxiety, spatial memory and sucrose preference in adolescent rats. Seven week old Sprague Dawley rats (n=18 male, n=18 female) received daily subcutaneous injections (40 µg/kg body weight) of BPA or vehicle for 12 days. Starting on day 6 of injections, subjects were tested on the elevated plus maze which provides a measure of anxiety, the open field test which provides a measure of anxiety and locomotor activity, and object placement, a measure of spatial memory. On the twelfth day of BPA administration, sucrose preference was tested using a standard two-bottle choice (tap versus sucrose solution). All rats gained weight during the study; there was a main effect of sex, but not BPA treatment on body weight. The results indicate that BPA exposure, regardless of sex, increased anxiety on both the elevated plus maze and open field. Spatial memory was impaired on the object recognition task with BPA animals spending significant less time with the object in the novel location than controls. Finally, a significant increase in sucrose consumption for both male and female subjects exposed to BPA was observed. The current data shows that short term BPA exposure, below the current reference safe daily limit of 50 µg/kg day set by the United States Environmental Protection Agency, during adolescent development increases anxiety, impairs spatial memory, and increases sucrose consumption independent of sex.

Adolescent exposure to Bisphenol-A increases anxiety and sucrose preference but impairs spatial memory in rats independent of sex.

Bisphenol-A (BPA), a common environmental endocrine disruptor, modulates estrogenic, androgenic, and antiandrogenic effects throughout the lifespan. We recently showed that low dose BPA exposure during adolescence increases anxiety and impairs spatial memory independent of sex. In this study, six week old Sprague Dawley rats (n=24 males, n=24 females) received daily subcutaneous injections (40 µg/kg bodyweight) of BPA or vehicle for one week. Serum corticosterone levels in response to a 1 h restraint stress and spine density were examined at age 7 (cohort 1) and 11 (cohort 2) weeks. Adolescent BPA exposure did not alter stress dependent corticosterone responses but decreased spine density on apical and basal dendrites of pyramidal cells in the medial prefrontal cortex (mPFC) and hippocampal CA1 region (CA1). Sex differences in spine density were observed on basal dendrites of the mPFC and CA1 with females having greater spine density than males. This sex difference was further augmented by both age and treatment, with results indicating that BPA-dependent decreases in spine density were more pronounced in males than females on mPFC basal dendrites. Importantly, the robust neuronal alterations were observed in animals exposed to BPA levels below the current U.S.E.P.A. recommended safe daily limit. These results are the first demonstrating that BPA given during adolescence leads to enduring effects on neural morphology at adulthood. Given that humans are routinely exposed to low levels of BPA through a variety of sources, the decreased spine density reported in both male and female rats after BPA exposure warrants further investigation.

Adolescent bisphenol-A exposure decreases dendritic spine density: role of sex and age.

We have previously demonstrated that adolescent exposure of rats to bisphenol-A (BPA), an environmental endocrine disrupter, increases anxiety, impairs spatial memory, and decreases dendritic spine density in the CA1 region of the hippocampus (CA1) and medial prefrontal cortex (mPFC) when measured in adolescents in both sexes. The present study examined whether the behavioral and morphological alterations following BPA exposure during adolescent development are maintained into adulthood. Male and female, adolescent rats received BPA, 40μg/kg/bodyweight, or control treatments for one week. In adulthood, subjects were tested for anxiety and locomotor activity, spatial memory, non-spatial visual memory, and sucrose preference. Additionally, stress-induced serum corticosterone levels and dendritic spine density in the mPFC and CA1 were measured. BPA-treated males, but not females, had decreased arm visits on the elevated plus maze, but there was no effect on anxiety. Non-spatial memory, object recognition, was also decreased in BPA treated males, but not in females. BPA exposure did not alter spatial memory, object placement, but decreased exploration during the tasks in both sexes. No significant group differences in sucrose preference or serum corticosterone levels in response to a stress challenge were found. However, BPA exposure, regardless of sex, significantly decreased spine density of both apical and basal dendrites on pyramidal cells in CA1 but had no effect in the mPFC. Current data are discussed in relation to BPA dependent changes, which were present during adolescence and did, or did not, endure into adulthood. Overall, adolescent BPA exposure, below the current reference safe daily limit set by the U.S.E.P.A., leads to alterations in some behaviors and neuronal morphology that endure into adulthood. 

Bisphenol-A exposure during adolescence leads to enduring alterations in cognition and dendritic spine density in adult male and female rats.

Chronic stress causes deleterious changes in physiological function in systems ranging from neural cells in culture to laboratory rodents, sub-human primates and humans. It is notable, however, that the vast majority of research in this area has been conducted in males. In this review, we provide information about chronic stress effects on cognition in female rodents and contrast it with responses in male rodents. In general, females show cognitive resilience to chronic stressors which impair male cognitive function using spatial tasks including the radial arm maze, radial arm water maze, Morris water maze, Y-maze and object placement. Moreover, stress often enhances female performance in some of these cognitive tasks. Memory in females is not affected by stress in non-spatial memory tasks like recognition memory and temporal order recognition memory while males show impaired memory following stress. We discuss possible bases for these sex-dependent differences including the use of different strategies by the sexes to solve cognitive tasks. Whether the sex differences result from changes in non-mnemonic factors is also considered. Sex-dependent differences in alcohol and drug influences on stress responses are also described. Finally, the role of neurally derived estradiol in driving sex differences and providing resilience to stress in females is shown. The importance of determining the nature and extent of sex differences in stress responses is that such differences may provide vital information for understanding why some stress related diseases have different incidence rates between the sexes and for developing novel therapeutic treatments.

Sex differences in chronic stress effects on cognition in rodents.

The endocrine disruptor, Bisphenol-A (BPA), alters many behavioral and neural parameters in rodents. BPA administration to gonadally intact adolescent rats increases anxiety, impairs spatial memory, and decreases dendritic spine density when measured in adulthood. Since BPA's action seems to be mediated through gonadal steroid receptors, the current experiments were done in ovariectomized (OVX) female rats to examine the effects on behavior and spine density of adolescent BPA exposure under controlled hormone conditions. OVX (postnatal day, PND, 21) female Sprague-Dawley rats (n = 66) received subcutaneous injections of BPA (40 μg/kg/bodyweight), 17β-Estradiol (E2, 50 μg/kg/bodyweight), or saline during adolescence (PND 38-49). Following the last injection brains were processed for Golgi impregnation (Exp1), behavioral and spine density in adolescence (Exp2), or in adulthood (Exp3). In Exp1, E2 increased spine density in CA1 pyramidal cells and BPA decreased spine density in granule cells of the dentate gyrus (DG). In Exp2, BPA impaired spatial memory on the object placement (OP) task, E2 increased spine density in CA1, BPA decreased spine density in the DG and the medial prefrontal cortex (mPFC). When measured in adulthood (Exp3), BPA impaired OP and object recognition (OR) performance, E2 increased spine density in CA1, and BPA decreased spine density in CA1, the mPFC and the DG. Results provide novel data on the effects of adolescent BPA in an OVX model and are compared to data in intact animals and within the context of understanding the importance of the profound neuronal alterations occurring during adolescent development.

Effects of adolescent Bisphenol-A exposure on memory and spine density in ovariectomized female rats: Adolescence vs adulthood.

Developmental exposure to Bisphenol A (BPA), an endocrine disrupting chemical, alters many behaviors and neural parameters in rodents and non-human-primates. The effects of BPA are mediated via gonadal hormone, primarily, estrogen receptors, and are not limited to the perinatal period since recent studies show impairments further into development. The studies described in this chapter address the effects of BPA administration during early adolescence on memory and dendritic spine density in intact male and female rats as well as ovariectomized (OVX) rats in late adolescence and show that some of these adolescent induced changes endure into adulthood. In general, BPA impairs spatial memory and induces decreases in dendritic spine density in the hippocampus and the medial prefrontal cortex, two areas important for memory. The effects of adolescent BPA in intact females are compared to OVX females in an attempt to address the importance of estrogens in the mechanism(s) underlying the profound neuronal alterations occurring during adolescent development. In addition, potential mechanisms by which acute and chronic BPA induce structural alterations are discussed. These studies suggest a complex interaction between low doses of BPA, gonadal state and neural development.

Article	Year
Chronic stress effects on memory: sex differences in performance and monoaminergic activity. Hormones and behavior\| PubMed ID: 12614634	2003
Sexually dimorphic effects of prenatal stress on cognition, hormonal responses, and central neurotransmitters. Endocrinology\| PubMed ID: 15142991	2004
Stress-induced changes in spatial memory are sexually differentiated and vary across the lifespan. Journal of neuroendocrinology\| PubMed ID: 16011489	2005
Aged rats: sex differences and responses to chronic stress. Brain research\| PubMed ID: 16919611	2006
Sex-dependent changes in anxiety, memory, and monoamines following one week of stress. Physiology & behavior\| PubMed ID: 19419681	2009
Chronically stressed female rats show increased anxiety but no behavioral alterations in object recognition or placement memory: a preliminary examination. Stress (Amsterdam, Netherlands)\| PubMed ID: 22168672	2012
Adolescent exposure to Bisphenol-A increases anxiety and sucrose preference but impairs spatial memory in rats independent of sex. Brain research\| PubMed ID: 23872220	2013
Adolescent bisphenol-A exposure decreases dendritic spine density: role of sex and age. Synapse (New York, N.Y.)\| PubMed ID: 24975924	2014
Bisphenol-A exposure during adolescence leads to enduring alterations in cognition and dendritic spine density in adult male and female rats. Hormones and behavior\| PubMed ID: 25554518	2015
Sex differences in chronic stress effects on cognition in rodents. Pharmacology, biochemistry, and behavior\| PubMed ID: 27566290	2017
Effects of adolescent Bisphenol-A exposure on memory and spine density in ovariectomized female rats: Adolescence vs adulthood. Hormones and behavior\| PubMed ID: 30465772	2019
A potential role for dendritic spines in bisphenol-A induced memory impairments during adolescence and adulthood. Vitamins and hormones\| PubMed ID: 32723549	2020

Rachel Bowman

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