Timing of methamphetamine exposure during adolescence differentially influences parvalbumin and perineuronal net immunoreactivity in the medial prefrontal cortex of female, but not male, rats.

Adolescence involves significant reorganization within the medial prefrontal cortex (mPFC), including modifications to inhibitory neurotransmission mediated through parvalbumin (PV) interneurons and their surrounding perineuronal nets (PNNs). These developmental changes, which result in increased PV neuron activity in adulthood, may be disrupted by drug use resulting in lasting changes in mPFC function and behavior. Methamphetamine (METH), which is a readily available drug used by some adolescents, increases PV neuron activity and could influence the activity-dependent maturational process of these neurons.

The last stage of development: The restructuring and plasticity of the cortex during adolescence especially at puberty.

There is considerable evidence of reorganization in the prefrontal cortex during adolescence in humans, as well as in rodents, where the cellular basis can be explored. Studies from my laboratory in the rat medial prefrontal cortex are reviewed here. In general, growth predominates before puberty.

Region- and age-specific effects of perinatal phthalate exposure on developmental cell death and adult anatomy of dorsal and ventral hippocampus and associated cognitive behaviors.

Humans are exposed to phthalates, a class of endocrine-disrupting chemicals used in food packaging/processing, PVC plastics, and personal care products. Gestational exposure may lead to adverse neurodevelopmental outcomes. In a rat model, perinatal exposure to an environmentally relevant mixture and dose of phthalates leads to increased developmental apoptosis in the medial prefrontal cortex (mPFC) and a subsequent reduction in neurons and in cognitive flexibility measured in adults of both sexes (Sellinger et al.

Brief postnatal exposure to bisphenol A affects apoptosis and gene expression in the medial prefrontal cortex and social behavior in rats with sex specificity.

Bisphenol A (BPA) is an endocrine disruptor found in polycarbonate plastics and exposure in humans is nearly ubiquitous and it has widespread effects on cognitive, emotional, and reproductive behaviors in both humans and animal models. In our laboratory we previously found that perinatal BPA exposure results in a higher number of neurons in the adult male rat prefrontal cortex (PFC) and less play in adolescents of both sexes. Here we examine changes in the rate of postnatal apoptosis in the rat prefrontal cortex and its timing with brief BPA exposure.

Changes in sex differences in neuroanatomical structure and cognitive behavior across the life span.

Sex differences occur in the structure and function of the rat cerebral cortex and hippocampus, which can change from the juvenile period through old age. Although the evidence is incomplete, it appears that in at least some portions of the cortex these differences develop due to the rise of ovarian hormones at puberty and are potentially not dependent on the perinatal rise in testosterone, which is essential for sexual differentiation of the hypothalamus and sexual behavior. During aging of female rats, the presence of continued ovarian hormone secretion after cessation of the estrous cycle also influences sex differences in neuroanatomical structure and cognitive behavior, resulting in nullification or reversal of sex differences seen in younger adults.

Perinatal phthalate exposure increases developmental apoptosis in the rat medial prefrontal cortex.

Phthalates are a class of endocrine disruptors found in a variety of consumer goods, and offspring can be exposed to these compounds during gestation and lactation. Our laboratory has found that perinatal exposure to an environmentally relevant mixture of phthalates resulted in a decrease in cognitive flexibility and in neuron number in the adult rat medial prefrontal cortex (mPFC). Here, we examine effects of phthalate treatment on prenatal cellular proliferation and perinatal apoptosis in the mPFC.

Impact of pubertal onset on region-specific Esr2 expression.

In female rats, pubertal onset is associated with maturation of the medial prefrontal cortex (mPFC) and mPFC-mediated behaviours. These behavioural and anatomical changes are likely a result of the effects of oestrogens at the nuclear oestrogen receptor (ER)β, which is expressed at higher levels than the ERα isoform in the adult mPFC. Researchers have previously quantified ERβ protein and Esr2 RNA in rodents during early postnatal development and adulthood, although an adolescent-specific trajectory of this receptor in the mPFC has not been documented.

Cell death in the male and female rat medial prefrontal cortex during early postnatal development.

Apoptosis, programmed cell death, is a critical component of neurodevelopment occurring in temporal, spatial, and at times, sex-specific, patterns across the cortex during the early postnatal period. During this time, the brain is particularly susceptible to environmental influences that are often used in animal models of neurodevelopmental disorders. In the present study, the timing of peak cell death was assessed by the presence of pyknotic cells in the male and female rat medial prefrontal cortex (mPFC), a cortical region that in humans, is often involved in developmental disorders.

Natural and Synthetic α-Tocopherol Modulate the Neuroinflammatory Response in the Spinal Cord of Adult -null Mice.

Background: Vitamin E (α-tocopherol, α-T) deficiency causes neurological pathologies. α-T supplementation improves outcomes, but the relative bioactivities of dietary natural and synthetic α-T in neural tissues are unknown.

Objective: The aim was to assess the effects of dietary α-T source and dose on oxidative stress and myelination in adult α-tocopherol transfer protein-null ( ) mouse cerebellum and spinal cord.

Adolescent stress during, but not after, pubertal onset impairs indices of prepulse inhibition in adult rats.

Exposure to stress during adolescence is a risk factor for developing several psychiatric disorders, many of which involve prefrontal cortex (PFC) dysfunction. The human PFC and analogous rodent medial prefrontal cortex (mPFC) continue to mature functionally and anatomically during adolescence, and some of these maturational events coincide with pubertal onset. As developing brain regions are more susceptible to the negative effects of stress, this may make puberty especially vulnerable.

The structural reorganization of the prefrontal cortex during adolescence as a framework for vulnerability to the environment.

Adolescence is a time of increased vulnerability to developing substance use disorders. In part, this may be due to the wide array of neural changes occurring during this time, many of which can be altered by environmental stimuli including drugs. In this review, we will examine the evidence for neuroanatomical changes during adolescence in the prefrontal cortex (PFC), an important neural region involved in decision making and reward processing.

Cortical reorganization during adolescence: What the rat can tell us about the cellular basis.

The human cortex, particularly the prefrontal cortex, decreases in volume during adolescence which indicates considerable pruning. There is consistent evidence from human, monkey and rat tissue that synapses, dendritic spines and dendrites are pruned during this time. However, our work with a rat model of adolescence shows that other cellular components are remodeling at this time as well.

Influences of age and pubertal status on number and intensity of perineuronal nets in the rat medial prefrontal cortex.

The prefrontal cortex (PFC) is a late developing region of the cortex, and its protracted maturation during adolescence may confer a period of plasticity. Closure of critical, or sensitive, periods in sensory cortices coincides with perineuronal net (PNN) expression, leading to enhanced inhibitory function and synaptic stabilization. PNN density has been found to increase across adolescence in the male rat medial PFC (mPFC).

Behavioral effects in adult rats exposed to low doses of a phthalate mixture during the perinatal or adolescent period.

Hormones influence neurodevelopment which can result in vulnerability to endocrine disruptors such as phthalates during both the perinatal period and adolescence. Using a rat model, we have previously shown that perinatal exposure to an environmentally relevant phthalate mixture at low doses results in cognitive flexibility deficits in adults and a reduction in neuron and synapse number within the medial prefrontal cortex. Here, we further examined the behavioral effects of exposure to an environmentally relevant mixture of phthalates at low doses during either perinatal development or adolescence.

Synthetic α-Tocopherol, Compared with Natural α-Tocopherol, Downregulates Myelin Genes in Cerebella of Adolescent Ttpa-null Mice.

Background: Vitamin E (α-tocopherol; α-T) deficiency causes spinocerebellar ataxia. α-T supplementation improves neurological symptoms, but little is known about the differential bioactivities of natural versus synthetic α-T during early life.

Objective: We assessed the effects of dietary α-T dose and source on tissue α-T accumulation and gene expression in adolescent α-tocopherol transfer protein-null (Ttpa-/-) mice.

Tissue-specific changes in and expression and DNA methylation with perinatal phthalate exposure.

Perinatal exposure to endocrine disrupting chemicals negatively impacts health, but the mechanism by which such toxicants damage long-term reproductive and metabolic function is unknown. Lipid metabolism plays a pivotal role in steroid hormone synthesis as well as energy utilization and storage; thus, aberrant lipid regulation may contribute to phthalate-driven health impairments. In order to test this hypothesis, we specifically examined epigenetic disruptions in lipid metabolism pathways after perinatal phthalate exposure.

Perinatal High-Fat Diet and Bisphenol A: Effects on Behavior and Gene Expression in the Medial Prefrontal Cortex.

Both high-fat diets (HFD) and bisphenol A (BPA), an environmental endocrine disruptor, are prevalent in industrialized societies. Previous studies have detected separate effects of BPA and HFD; however, none have assessed possible interactive effects. Here, pregnant dams consumed 0, 40, or 400 µg BPA/kg/day and were fed either a control (CON; 15.

Perinatal Exposure to an Environmentally Relevant Mixture of Phthalates Results in a Lower Number of Neurons and Synapses in the Medial Prefrontal Cortex and Decreased Cognitive Flexibility in Adult Male and Female Rats.

The growth and organization of the developing brain are known to be influenced by hormones, but little is known about whether disruption of hormones affects cortical regions, such as mPFC. This region is particularly important given its involvement in executive functions and implication in the pathology of many neuropsychiatric disorders. Here, we examine the long-term effects of perinatal exposure to endocrine-disrupting compounds, the phthalates, on the mPFC and associated behavior.

Age- and sex-dependent effects of methamphetamine on cognitive flexibility and 5-HT receptor localization in the orbitofrontal cortex of Sprague-Dawley rats.

Adolescents and females experience worse outcomes of drug use compared to adults and males. This could result from age- and sex-specific consequences of drug exposure on brain function and cognitive behavior. In the current study, we examined whether a history of intravenous methamphetamine (METH) self-administration impacted cognitive flexibility and 5-HTR localization in the orbitofrontal cortex (OFC) in an age- and sex-dependent manner.

Effects of Perinatal Exposure to Phthalates and a High-Fat Diet on Maternal Behavior and Pup Development and Social Play.

Humans are ubiquitously exposed to many phthalates, a class of endocrine-disrupting chemicals commonly used in many consumer goods, and diet, especially fatty food, is presumed to be a major source of exposure. Here, we use a rat model of human prenatal exposure to investigate the potential interactive effects of an environmentally relevant mixture of phthalates and a maternal high-fat diet (HFD). From gestation through postnatal day (P)10, dams consumed the mixture of phthalates (0, 200, or 1000 μg/kg/d) and were fed a control diet or HFD.

Innervation of the medial prefrontal cortex by tyrosine hydroxylase immunoreactive fibers during adolescence in male and female rats.

Adolescence is associated with continued maturation of the cerebral cortex, particularly the medial prefrontal cortex (mPFC). We have previously documented pruning in the number of neurons, dendrites, and synapses in the rat mPFC from preadolescence to adulthood, with the period of pubertal onset being particularly important. We hypothesized that dopaminergic innervation of this region, critical for executive functions, would also be influenced by pubertal onset.

Beta-hydroxy-beta-methylbutyrate (HMB) ameliorates age-related deficits in water maze performance, especially in male rats.

Beta-hydroxy-beta-methylbutyrate (HMB) is commonly supplemented to maintain muscle in elderly and clinical populations and has potential as a nootropic. Previously, we have shown that in both male and female rats, long-term HMB supplementation prevents age-related dendritic shrinkage within the medial prefrontal cortex (mPFC) and improves cognitive flexibility and working memory performance that are both age- and sex-specific. In this study, we further explore the cognitive effects by assessing visuospatial learning and memory with the Morris water maze.

Synaptic number changes in the medial prefrontal cortex across adolescence in male and female rats: A role for pubertal onset.

Adolescence is a unique period of development, marked by maturation of the prefrontal cortex (PFC), a region important for executive functioning. During this time, the human PFC decreases in overall volume and thickness. Likewise in adolescent rodents, losses of neurons, dendrites, dendritic spines and neurotransmitter receptors have been documented within the medial prefrontal cortex (mPFC), sometimes with sex and layer specificity.

Pubertal onset as a critical transition for neural development and cognition.

Adolescence, broadly defined as the period between childhood and adulthood, is characterized by a variety of neuroanatomical and behavioral changes. In human adolescents, the cerebral cortex, especially the prefrontal cortex, decreases in size while the cortical white matter increases. Puberty appears to be an important factor in both of these changes.