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Introduction: Fragile X syndrome is an inherited X-linked disorder associated with intellectual disabilities that begin in childhood and last a lifetime. The symptoms overlap with autism spectrum disorder, and the syndrome predominantly affects males. Consequently, FXS research tends to favor analysis of social behaviors in males, leaving a gap in our understanding of other behavioral traits, especially in females. Methods: We used a mouse model of FXS to analyze developmental, behavioral, neurochemical, and transcriptomic profiles in males and females. Results: Our behavioral assays demonstrated locomotor hyperactivity, motor impulsivity, increased "approach" behavior in an approach-avoidance assay, and deficits in nest building behavior. Analysis of brain neurotransmitter content revealed deficits in striatal GABA, glutamate, and serotonin content. RNA sequencing of the ventral striatum unveiled expression changes associated with neurotransmission as well as motivation and substance use pathways. Sex differences were identified in nest building behavior, striatal neurotransmitter content, and ventral striatal gene expression. Discussion: In summary, our study identified sex differences in specific behavioral, neurotransmitter, and gene expression phenotypes and gene set enrichment analysis identified significant enrichment of pathways associated with motivation and drug reward. [ABSTRACT FROM AUTHOR]

Objective: We offer an overview of ADHD research using mouse models of nicotine exposure. Method: Nicotine exposure of C57BL/6 or Swiss Webster mice occurred during prenatal period only or during the prenatal and the pre-weaning periods. Behavioral, neuroanatomical and neurotransmitter assays were used to investigate neurobiological mechanisms of ADHD and discover candidate ADHD medications. Results: Our studies show that norbinaltorphimine, a selective kappa opioid receptor antagonist is a candidate novel non-stimulant ADHD treatment and that a combination of methylphenidate and naltrexone has abuse deterrent potential with therapeutic benefits for ADHD. Other studies showed transgenerational transmission of ADHD-associated behavioral traits and demonstrated that interactions between untreated ADHD and repeated mild traumatic brain injury produced behavioral traits not associated with either condition alone. Conclusion: Preclinical models contribute to novel insights into ADHD neurobiology and are valuable tools for drug discovery and translation to benefit humans with ADHD. [ABSTRACT FROM AUTHOR]

Aim: Cancer patients undergoing chemotherapy report cognitive changes collectively termed "chemo brain." Neuroinflammation is among the factors believed to contribute to "chemo brain" suggesting a potential beneficial role for anti-inflammatory drugs in cancer patients undergoing chemotherapy. We investigated whether the non-steroidal anti-inflammatory drug naproxen influenced hippocampal inflammation in non-tumor bearing female mice receiving the chemotherapy drug cyclophosphamide (CP). Materials and methods: Intact and ovariectomized C57BL/6 mice were used to examine potential role of ovarian hormones on neuroinflammation. The mice were placed on naproxen (375 ppm) or control diet, and a week later CP (100 mg/kg; i.p.) was administered every 3 days for 2 weeks. We analyzed hippocampal inflammatory biomarkers, anxiety-like behavior, spatial working memory, exploratory behavior, spontaneous locomotor activity and depression-like behavior. Results: CP produced significant effects on anti-inflammatory but not pro-inflammatory biomarkers. However, CP and naproxen in combination produced significant effects on both pro- and anti- inflammatory biomarkers. Naproxen and ovariectomy individually produced significant effects on pro- and anti-inflammatory biomarkers as well. Working memory and depression-like behavior were not significantly influenced by CP, naproxen or ovariectomy individually although CP and ovariectomy produced significant interaction effects on depression-like behavior. Exploratory behavior and locomotor activity showed significant effects of CP, and interaction between CP and naproxen was significant for locomotor activity. Conclusions: Ovariectomy, naproxen and a combination of CP and naproxen upregulate hippocampal pro- and anti- inflammatory biomarkers. None of the factors individually produce significant behavioral changes that could be consistent with chemo brain, although CP and ovariectomy in combination produced significant effects on depression-like behavior, a co-morbidity of chemo brain. [ABSTRACT FROM AUTHOR]

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.tins.2009.05.003 Byline: Verne S. Caviness (1), Richard S. Nowakowski (2), Pradeep G. Bhide (1) Abstract: Each of the five cellular layers of the cerebral neocortex is composed of a specific number of a single predominant 'class' of projection neuron. The projection neuron class is defined by its unique morphology and axonal projections to other areas of the brain. Precursor cell populations lining the embryonic lateral ventricles produce the projection neurons. The mechanisms regulating precursor cell proliferation also regulate total numbers of neurons produced at specific developmental periods and destined to a specific neocortical layer. Because the newborn neurons migrate relatively long distances to reach their final layer destinations, it is often assumed that the mechanisms governing acquisition of neuronal-class-specific characteristics, many of which become evident after neuron production, are independent of the mechanisms governing neuron production. We review evidence that suggests that the two mechanisms might be linked via operations of Notch1 and p27.sup.Kip1, molecules known to regulate precursor cell proliferation and neuron production. Author Affiliation: (1) Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA (2) UMDNJ-RWJ Medical School, Piscataway, NJ 08854, USA

Objective: Based on emerging preclinical findings suggesting that paternal smoking at conception may be a risk for ADHD in the offspring, we investigated whether a similar effect can be observed in humans. Method: We analyzed data from an opportunistic dataset of girl probands with (N = 140) and without (N = 122) ADHD with available information on paternal smoking at conception. Data were analyzed using Pearson's chi-square tests and multiple logistic regression. Results: ADHD probands had a significantly higher rate of paternal smoking at conception than controls (35% vs. 23%, χ2 = 3.82, p = .05) with a significant odds ratio of 1.5. However, the association lost significance after controlling for paternal ADHD, most likely due to limited statistical power. Conclusion: While preliminary, findings suggest that paternal smoking at conception may be a risk factor for ADHD in the offspring. [ABSTRACT FROM AUTHOR]